WorldWideScience

Sample records for amphetamines

  1. Amphetamines

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Amphetamines KidsHealth > For Teens > Amphetamines A A A What's ... How Can Someone Quit? Avoiding Amphetamines What Are Amphetamines? Amphetamines are stimulants. They speed up functions in ...

  2. Amphetamine

    Science.gov (United States)

    ... and children. Amphetamine (Evekeo) is used to treat narcolepsy (a sleep disorder that causes excessive daytime sleepiness ... or without food. For treatment of ADHD or narcolepsy, the immediate-release tablet is usually taken with ...

  3. Amphetamine derivative related deaths.

    Science.gov (United States)

    Lora-Tamayo, C; Tena, T; Rodríguez, A

    1997-02-28

    Amphetamine its methylendioxy (methylendioxyamphetamine methylenedioxymethylamphetamine, methylenedioxyethylamphetamine) and methoxy derivatives (p-methoxyamphetamine and p-methoxymethylamphetamine) are widely abused in Spanish society. We present here the results of a systematic study of all cases of deaths brought to the attention of the Madrid department of the Instituto Nacional de Toxicologia from 1993 to 1995 in which some of these drugs have been found in the cadaveric blood. The cases were divided into three categories: amphetamine and derivatives, amphetamines and alcohol, amphetamines and other drugs. Data on age, sex, clinical symptoms, morphological findings, circumstances of death, when known, and concentration of amphetamine derivatives, alcohol and other drugs in blood are given for each group. The information provided here may prove to be useful for the forensic interpretation of deaths which are directly or indirectly related to abuse of amphetamine derivatives.

  4. Amphetamines and Sports Performance.

    Science.gov (United States)

    Cooter, G. Rankin

    1980-01-01

    A large number of athletes have resorted to drugs to improve performance in competition. Research literature on the use of amphetamines, both pro and con, is currently confounded with poor research designs and lack of controls, and further research is needed. (CJ)

  5. Toxicity of amphetamines: an update.

    Science.gov (United States)

    Carvalho, Márcia; Carmo, Helena; Costa, Vera Marisa; Capela, João Paulo; Pontes, Helena; Remião, Fernando; Carvalho, Félix; Bastos, Maria de Lourdes

    2012-08-01

    Amphetamines represent a class of psychotropic compounds, widely abused for their stimulant, euphoric, anorectic, and, in some cases, emphathogenic, entactogenic, and hallucinogenic properties. These compounds derive from the β-phenylethylamine core structure and are kinetically and dynamically characterized by easily crossing the blood-brain barrier, to resist brain biotransformation and to release monoamine neurotransmitters from nerve endings. Although amphetamines are widely acknowledged as synthetic drugs, of which amphetamine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) are well-known examples, humans have used natural amphetamines for several millenniums, through the consumption of amphetamines produced in plants, namely cathinone (khat), obtained from the plant Catha edulis and ephedrine, obtained from various plants in the genus Ephedra. More recently, a wave of new amphetamines has emerged in the market, mainly constituted of cathinone derivatives, including mephedrone, methylone, methedrone, and buthylone, among others. Although intoxications by amphetamines continue to be common causes of emergency department and hospital admissions, it is frequent to find the sophism that amphetamine derivatives, namely those appearing more recently, are relatively safe. However, human intoxications by these drugs are increasingly being reported, with similar patterns compared to those previously seen with classical amphetamines. That is not surprising, considering the similar structures and mechanisms of action among the different amphetamines, conferring similar toxicokinetic and toxicological profiles to these compounds. The aim of the present review is to give an insight into the pharmacokinetics, general mechanisms of biological and toxicological actions, and the main target organs for the toxicity of amphetamines. Although there is still scarce knowledge from novel amphetamines to draw mechanistic insights, the long-studied classical

  6. Psychophysiological aspects of amphetamine-methamphetamine abuse.

    Science.gov (United States)

    Murray, J B

    1998-03-01

    Abuse of amphetamines-methamphetamines has increased worldwide. Profiles of abusers, effects of different methods of administration, and research on amphetamine psychosis are reviewed, along with research on psychophysiological mechanisms, addictive potential, and psychotherapeutic strategies.

  7. Amphetamine. Report Series 28, No. 1.

    Science.gov (United States)

    National Inst. on Drug Abuse (DHEW/PHS), Rockville, MD. National Clearinghouse for Drug Abuse Information.

    This report, prepared by the National Clearinghouse for Drug Abuse Information, presents substantial information on the use and abuse of the drug "family" known as amphetamines. A brief history of the drug is given, along with its basic pharmacology. The current medical uses for amphetamines include: (1) short-term treatment of obesity,…

  8. Amphetamine Abuse Related Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Archana Sinha

    2016-01-01

    Full Text Available Amphetamine abuse is a global problem. The cardiotoxic manifestations like acute myocardial infarction (AMI, heart failure, or arrhythmia related to misuse of amphetamine and its synthetic derivatives have been documented but are rather rare. Amphetamine-related AMI is even rarer. We report two cases of men who came to emergency department (ED with chest pain, palpitation, or seizure and were subsequently found to have myocardial infarction associated with the use of amphetamines. It is crucial that, with increase in amphetamine abuse, clinicians are aware of this potentially dire complication. Patients with low to intermediate risk for coronary artery disease with atypical presentation may benefit from obtaining detailed substance abuse history and urine drug screen if deemed necessary.

  9. 21 CFR 862.3100 - Amphetamine test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Amphetamine test system. 862.3100 Section 862.3100....3100 Amphetamine test system. (a) Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements...

  10. Urethralism concomitant with amphetamine abuse

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    Bang-Ping Jiann

    2014-09-01

    Full Text Available Urethralism is a paraphilia disorder in which a person exhibits the habitual self-insertion of a foreign body into the urethra to achieve sexual gratification. We report a patient who habitually inserted a foreign body into his urethra and abused amphetamines to cope with stress. A 48-year-old man presented at the emergency room because of urine leakage from the penile base. Prior to this incident, he had been admitted to hospital 10 times from 2000 to 2005 for the removal of foreign bodies from the lower urinary tract. The patient also reported repeatedly inhaling a high dose of amphetamine to reach a “high” status prior to inserting a foreign body into his urethra. After the successful removal of the foreign bodies, the patient was referred to a psychiatrist for management in coping with stress and illicit drug withdrawal. Psychiatric support and treatment appeared to have a beneficial effect on his sexual behavior. In the management of a case involving recurrent insertion of a foreign body into the lower urinary tract, clinicians should enquire about a history of drug abuse and consult the psychiatry department regarding stress management and drug abstinence.

  11. Small volume liquid extraction of amphetamines in saliva.

    Science.gov (United States)

    Meng, Pinjia; Wang, Yanyan

    2010-04-15

    The present study introduced a procedure of small volume liquid extraction of amphetamines, including amphetamine (AM); methamphetamine (MA); 3,4-methylenedioxyamphetamine (MDA); 3,4-methylenemethamphtamine (MDMA), in saliva. Extraction efficiencies were compared between the conventional volume liquid phase extraction (LPE) and the small volume one, in which amphetamine abusers, and was proven to be practical for detecting trace amounts of amphetamines in saliva.

  12. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Shim, Irene; White, Peter Cyril

    2012-01-01

    Theoretical calculations and preliminary measurements of vibrational Raman optical activity (ROA) spectra of different species of amphetamine (amphetamine and amphetamine-H+) are reported for the first time. The quantum chemical calculations were carried out as hybrid ab initio DFT-molecular orbi...

  13. D-amphetamine and delinquency: hyperkinesis persisting?

    Science.gov (United States)

    Maletzky, B M

    1974-12-01

    The clinical efficacy of d-amphetamine for delinquent behavior in adolescents and the relationships between such delinquency and hyperactivity of childhood were explored employing the methods of sequential analysis. Fourteen subject pairs of delinquent teenagers were examined, and a significant positive effect documented for d-amphetamine as compared to placebo when both were added to an ongoing psychotherapeutic regimen. Tolerance, withdrawal, and euphoria were not associated with d-amphetamine's use in the experimental subjects. Parallels were drawn between d-amphetamine' s effects in delinquent adolescents and hyperactive children; a re-analysis of the data demonstrated surprisingly close links between a history or presence of hyperactive traits and a clinical response to d-amphetamine. Difficulties in employing d-amphetamine in this age group are acknowledged and suggestions for further research offered. The notion that children "outgrow" hyperactivity may be simplistic: hyperactive children as teenagers may not be overly active; however, they continue to manifest behavioral difficulties, primarily of an antisocial nature. While this may be partially explained on the basis of negative aspects in their upbringing, there is some evidence of hereditary and neurologic mechanisms at fault. One method of documenting continuing neurologic dysfunction in the hyperactive child turned teenager is by direct examination. A number of investigators have demonstrated electroencephalographic abnormalities in juvenile delinquents, many of whom had histories of hyperactivity as children. More recently, this kind of individual has been shown to suffer some frontal lobe dysfunction and to manifest subtle, but definite, abnormalities on intensive neurological examination. Continuing central nervous system dysfunction in delinquency might also be demonstrated by pharmacologic means: should delinquent adolescents respond to drugs that help the hyperactive child, similar mechanisms

  14. Enantioselective degradation of amphetamine-like environmental micropollutants (amphetamine, methamphetamine, MDMA and MDA) in urban water.

    Science.gov (United States)

    Evans, Sian E; Bagnall, John; Kasprzyk-Hordern, Barbara

    2016-08-01

    This paper aims to understand enantioselective transformation of amphetamine, methamphetamine, MDMA (3,4-methylenedioxy-methamphetamine) and MDA (3,4-methylenedioxyamphetamine) during wastewater treatment and in receiving waters. In order to undertake a comprehensive evaluation of the processes occurring, stereoselective transformation of amphetamine-like compounds was studied, for the first time, in controlled laboratory experiments: receiving water and activated sludge simulating microcosm systems. The results demonstrated that stereoselective degradation, via microbial metabolic processes favouring S-(+)-enantiomer, occurred in all studied amphetamine-based compounds in activated sludge simulating microcosms. R-(-)-enantiomers were not degraded (or their degradation was limited) which proves their more recalcitrant nature. Out of all four amphetamine-like compounds studied, amphetamine was the most susceptible to biodegradation. It was followed by MDMA and methamphetamine. Photochemical processes facilitated degradation of MDMA and methamphetamine but they were not, as expected, stereoselective. Preferential biodegradation of S-(+)-methamphetamine led to the formation of S-(+)-amphetamine. Racemic MDMA was stereoselectively biodegraded by activated sludge which led to its enrichment with R-(-)-enantiomer and formation of S-(+)-MDA. Interestingly, there was only mild stereoselectivity observed during MDMA degradation in rivers. This might be due to different microbial communities utilised during activated sludge treatment and those present in the environment. Kinetic studies confirmed the recalcitrant nature of MDMA.

  15. Amphetamines in the Treatment of Hyperkinetic Children

    Science.gov (United States)

    Grinspoon, Lester; Singer, Susan B.

    1973-01-01

    Article is a literature review, but a literature review with definite policy implications. It concerns the widespread use of amphetamines in the nation's schools to control a syndrome which doctors and medical researchers call "hyperkinetic behavior disorder," or "minimal brain dysfunction," and which teachers and parents know as "hyperactivity".…

  16. The Nonmedical Use of Amphetamines among the College Age Group: Recent Research concerning Epidemiology and Toxicity.

    Science.gov (United States)

    Nicholi, Armand M., Jr.

    1984-01-01

    Amphetamines have a significant role in nontherapeutic drug use by college students. A brief history of amphetamine use by college students is presented. Considerable data implicate amphetamines in producing serious psychological and biological adverse effects. (Author/DF)

  17. The fast and furious : Cocaine, amphetamines and harm reduction

    NARCIS (Netherlands)

    J-P.C. Grund (Jean-Paul); P. Coffin (Philip); M. Jauffret-Roustide (Marie); M. Dijkstra (Minke); D. de Bruin (Dick); P. Blanken (Peter)

    2010-01-01

    textabstractCocaine and amphetamines (‘stimulants’) are distinct central nervous system stimulants with similar effects (Pleuvry, 2009; Holman, 1994). Cocaine is a crystalline tropane alkaloid extracted from coca leaves. Amphetamines are a subclass of phenylethylamines with primarily stimulant effec

  18. Comparison of periodontal manifestations in amphetamine and opioids' consumers

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi

    2016-03-01

    Full Text Available Background: Drug abuse is one of the most important etiologic and deteriorating factors in periodontal disease. Amphetamines and opioids, the most commonly used drugs worldwide, play an important role in this regard. The aim of this study was to compare the periodontal status of amphetamines and opioids consumers in Kermanshah city, Iran in 1393. Methods: Three drug rehabilitation clinics were selected randomly in Kermanshah. According to inclusion and exclusion criteria, 20 amphetamine consumers and 20 opioid consumers were selected randomly and participated in this study. A questionnaire for drug use and periodontal variables was designed. The collected data were entered into SPSS-18 software and Mann-Whitney and t-test were used for statistical analysis. Results: Pocket depth, gingival index and gingival bleeding in amphetamines users were more than those in opioids consumers (P<0.021. Plaque index and gingival recession in opioids users were more than those of amphetamines consumers (P<0.001. The number of periodontal disease cases in amphetamines group were 13 persons (65% and in opioids group 8 persons (40%. Conclusion: Our study showed that periodontal hygine in amphetamine consumers was worse than opioid consumers.

  19. Narcolepsy Treated with Racemic Amphetamine during Pregnancy and Breastfeeding.

    Science.gov (United States)

    Öhman, Inger; Wikner, Birgitta Norstedt; Beck, Olof; Sarman, Ihsan

    2015-08-01

    This case report describes a woman with narcolepsy treated with racemic amphetamine (rac-amphetamine) during pregnancy and breastfeeding with follow-up on the infant's development up to 10 months of age. The pregnancy outcome and the pharmacokinetics of rac-amphetamine were studied during breastfeeding. The pregnancy and the delivery were uneventful. Concentrations of rac-amphetamine were determined in the plasma of the mother and infant, and in the breast milk with a liquid chromatography-mass spectrometry method. Samples were obtained at 2, 5, and 9 weeks postpartum. The transfer of rac-amphetamine to the breast milk was extensive (mean milk/maternal plasma concentration ratio approximately 3). The breastfed infant had a low plasma concentration of rac-amphetamine (about 9% of the maternal plasma level) and the calculated relative infant dose was low (2%). No adverse effects were observed in the breastfed infant. The infant's somatic and psychomotor development up to 10 months of age was normal. Further studies of amphetamine prescribed for medical reasons during pregnancy and lactation are needed.

  20. Amphetamine enhances retrieval following diverse sources of forgetting.

    Science.gov (United States)

    Quartermain, D; Judge, M E; Jung, H

    1988-01-01

    The generality of amphetamine-induced retrieval enhancement was investigated by determining whether pretest administration could alleviate different types of forgetting. Thirsty mice were punished for licking a water tube following a period of free drinking. Forgetting of the conditioned drink suppression was induced in different groups of animals by; protein synthesis inhibition, cholinergic receptor blockade, inhibition of norepinephrine synthesis, stimulation of serotonin receptors, electroconvulsive shock, a 2.5 month training to test interval and the use of senescent animals with an endogenous memory defect. Thirty min prior to testing mice were injected with either saline or with 2 mg/kg d-amphetamine sulphate. Results showed that amphetamine produced a highly significant improvement in remembering in all of the forgetting treatment groups. It is concluded that amphetamine can alleviate forgetting caused by widely diverse etiologies probably by activating a nonspecific general retrieval system.

  1. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    OpenAIRE

    Panikkath, Ragesh; Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up.

  2. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    Science.gov (United States)

    Panikkath, Deepa

    2016-01-01

    A 43-year-old woman presented with acute lower intestinal bleeding requiring blood transfusion. Multiple initial investigations did not reveal the cause of the bleeding. Colonoscopy performed 2 days later showed features suggestive of ischemic colitis. On detailed history, the patient admitted to using amphetamines, and her urine drug screen was positive for them. She was managed conservatively and advised not to use amphetamines again. She did not have any recurrence on 2-year follow-up. PMID:27365888

  3. Occurrence and Potential Biological Effects of Amphetamine on Stream Communities.

    Science.gov (United States)

    Lee, Sylvia S; Paspalof, Alexis M; Snow, Daniel D; Richmond, Erinn K; Rosi-Marshall, Emma J; Kelly, John J

    2016-09-06

    The presence of pharmaceuticals, including illicit drugs in aquatic systems, is a topic of environmental significance because of their global occurrence and potential effects on aquatic ecosystems and human health, but few studies have examined the ecological effects of illicit drugs. We conducted a survey of several drug residues, including the potentially illicit drug amphetamine, at 6 stream sites along an urban to rural gradient in Baltimore, Maryland, U.S.A. We detected numerous drugs, including amphetamine (3 to 630 ng L(-1)), in all stream sites. We examined the fate and ecological effects of amphetamine on biofilm, seston, and aquatic insect communities in artificial streams exposed to an environmentally relevant concentration (1 μg L(-1)) of amphetamine. The amphetamine parent compound decreased in the artificial streams from less than 1 μg L(-1) on day 1 to 0.11 μg L(-1) on day 22. In artificial streams treated with amphetamine, there was up to 45% lower biofilm chlorophyll a per ash-free dry mass, 85% lower biofilm gross primary production, 24% greater seston ash-free dry mass, and 30% lower seston community respiration compared to control streams. Exposing streams to amphetamine also changed the composition of bacterial and diatom communities in biofilms at day 21 and increased cumulative dipteran emergence by 65% and 89% during the first and third weeks of the experiment, respectively. This study demonstrates that amphetamine and other biologically active drugs are present in urban streams and have the potential to affect both structure and function of stream communities.

  4. Mitochondria: key players in the neurotoxic effects of amphetamines.

    Science.gov (United States)

    Barbosa, Daniel José; Capela, João Paulo; Feio-Azevedo, Rita; Teixeira-Gomes, Armanda; Bastos, Maria de Lourdes; Carvalho, Félix

    2015-10-01

    Amphetamines are a class of psychotropic drugs with high abuse potential, as a result of their stimulant, euphoric, emphathogenic, entactogenic, and hallucinogenic properties. Although most amphetamines are synthetic drugs, of which methamphetamine, amphetamine, and 3,4-methylenedioxymethamphetamine ("ecstasy") represent well-recognized examples, the use of natural related compounds, namely cathinone and ephedrine, has been part of the history of humankind for thousands of years. Resulting from their amphiphilic nature, these drugs can easily cross the blood-brain barrier and elicit their well-known psychotropic effects. In the field of amphetamines' research, there is a general consensus that mitochondrial-dependent pathways can provide a major understanding concerning pathological processes underlying the neurotoxicity of these drugs. These events include alterations on tricarboxylic acid cycle's enzymes functioning, inhibition of mitochondrial electron transport chain's complexes, perturbations of mitochondrial clearance mechanisms, interference with mitochondrial dynamics, as well as oxidative modifications in mitochondrial macromolecules. Additionally, other studies indicate that amphetamines-induced neuronal toxicity is closely regulated by B cell lymphoma 2 superfamily of proteins with consequent activation of caspase-mediated downstream cell death pathway. Understanding the molecular mechanisms at mitochondrial level involved in amphetamines' neurotoxicity can help in defining target pathways or molecules mediating these effects, as well as in developing putative therapeutic approaches to prevent or treat the acute- or long-lasting neuropsychiatric complications seen in human abusers.

  5. Abuse of amphetamines and structural abnormalities in the brain.

    Science.gov (United States)

    Berman, Steven; O'Neill, Joseph; Fears, Scott; Bartzokis, George; London, Edythe D

    2008-10-01

    We review evidence that structural brain abnormalities are associated with abuse of amphetamines. A brief history of amphetamine use/abuse and evidence for toxicity is followed by a summary of findings from structural magnetic resonance imaging (MRI) studies of human subjects who had abused amphetamines and children who were exposed to amphetamines in utero. Evidence comes from studies that used a variety of techniques including manual tracing, pattern matching, voxel-based, tensor-based, or cortical thickness mapping, quantification of white matter signal hyperintensities, and diffusion tensor imaging. Ten studies compared controls to individuals who were exposed to methamphetamine. Three studies assessed individuals exposed to 3-4-methylenedioxymethamphetamine (MDMA). Brain structural abnormalities were consistently reported in amphetamine abusers, as compared to control subjects. These included lower cortical gray matter volume and higher striatal volume than control subjects. These differences might reflect brain features that could predispose to substance dependence. High striatal volumes might also reflect compensation for toxicity in the dopamine-rich basal ganglia. Prenatal exposure was associated with striatal volume that was below control values, suggesting that such compensation might not occur in utero. Several forms of white matter abnormality are also common and may involve gliosis. Many of the limitations and inconsistencies in the literature relate to techniques and cross-sectional designs, which cannot infer causality. Potential confounding influences include effects of pre existing risk/protective factors, development, gender, severity of amphetamine abuse, abuse of other drugs, abstinence, and differences in lifestyle. Longitudinal designs in which multimodal datasets are acquired and are subjected to multivariate analyses would enhance our ability to provide general conclusions regarding the associations between amphetamine abuse and brain

  6. Association of Leukocytosis with Amphetamine and Cocaine Use

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    John R. Richards

    2014-01-01

    Full Text Available Objective. Determining the etiology of unexplained leukocytosis in asymptomatic patients may incur unnecessary testing, cost, and prolonged emergency department stay. The objective was to delineate if use of amphetamines and/or cocaine is a factor. Methods. For two years we reviewed all psychiatric patients presenting for medical clearance with exclusions for infection, epilepsy, trauma, or other nonpsychiatric medical conditions. Results. With a total of 1,206 patients, 877 (72.7% amphetamines/cocaine-negative drug screen controls had mean WBC 8.4±2.6×103/µL. The 240 (19.9% amphetamines-positive, cocaine-negative, patients had WBC 9.4±3.3×103/µL (P<0.0001. The 72 (6.0% amphetamines-negative, cocaine-positive, patients had WBC 7.1±1.8×103/µL (P<0.0001. The remaining 17 (1.4% amphetamines/cocaine-positive patients had WBC 10.0±4.2×103/µL (P=0.01. Amphetamines-positive patients had a supranormal WBC ratio significantly higher than controls (23.8% versus 14.8%, P=0.001, whereas only one cocaine-positive patient had a supranormal WBC count, with significantly lower ratio (1.4%, P=0.0003. Conclusion. Use of amphetamines, not cocaine, may be associated with idiopathic leukocytosis. This may be explained by unique pharmacologic, neuroendocrine, and immunomodulatory differences.

  7. Amphetamines, the pregnant woman and her children: a review.

    Science.gov (United States)

    Oei, J L; Kingsbury, A; Dhawan, A; Burns, L; Feller, J M; Clews, S; Falconer, J; Abdel-Latif, M E

    2012-10-01

    The objective of this study is to review and summarize available evidence regarding the impact of amphetamines on pregnancy, the newborn infant and the child. Amphetamines are neurostimulants and neurotoxins that are some of the most widely abused illicit drugs in the world. Users are at high risk of psychiatric co-morbidities, and evidence suggests that perinatal amphetamine exposure is associated with poor pregnancy outcomes, but data is confounded by other adverse factors associated with drug-dependency. Data sources are Government data, published articles, conference abstracts and book chapters. The global incidence of perinatal amphetamine exposure is most likely severely underestimated but acknowledged to be increasing rapidly, whereas exposure to other drugs, for example, heroin, is decreasing. Mothers known to be using amphetamines are at high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their infants may escape detection, because the signs of withdrawal are usually less pronounced than opiate-exposed infants. There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide concern, but robust research, especially for childhood outcomes, remains scarce. We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase provision of early-intervention services for affected children and their families.

  8. Terahertz spectroscopic investigation of methylenedioxy amphetamine

    Science.gov (United States)

    Wang, Guangqin; Shen, Jingling

    2008-03-01

    Experimental measurement and theoretical analysis of THz spectrum for methylenedioxy amphetamine are introduced. The refractive index and absorption coefficient of the sample were observed by terahertz time-domain spectroscopy (THz-TDS) technique in the range of 0.2~2.6 THz. It exhibits obvious absorption feature at 1.40 THz and weak THz absorption at around 1.68 and 2.21 THz. The spectral absorption characteristic in THz band was useful for the inspection and identification of drugs using THz-TDS. The theoretical calculation was performed using Density functional theory (DFT) with the GAUSSIAN 03 software package. Fully geometry optimization and frequency analysis of the optimized structure were performed at the B3LYP/6-21G levels. The simulated absorption spectrum was in agreement with the experimental data, and can hence be used for the assignment of observed THz spectrum. The theoretical simulation result showed that absorption peaks mainly result from intra-molecule and inter-molecule vibrations, different absorption peaks are corresponding to different vibrational modes and intensity. So the combination of the THz-TDS and DFT is an effective way to investigate characteristic spectra of illicit drugs.

  9. Medico-legal aspect of amphetamine-related deaths

    Directory of Open Access Journals (Sweden)

    Karol Kula

    2014-12-01

    Full Text Available The subject of the work included 41 cases of death in which amphetamine was involved as the direct or indirect cause. Identification and determination of xenobiotics in blood samples collected from post-mortem cases were performed by high-performance liquid chromatography coupled with tandem mass spectrometry with electrospray ionisation (HPLC-ESI-MS-MS. Only for two cases was the cause of death amphetamine poisoning. In most of the investigated cases the death was caused by poisoning due to complex amphetamine and other psychoactive substances (e.g. opiates, benzodiazepines, cocaine. In other cases, multi-organ damage (fall from a height, traffic accident, a puncture wound and wound incised, drowning, or asphyxiation by hanging were reported. It can be explained as risky, murderous, or suicidal actions of people who were under the influence of amphetamines. The presented paper focuses on the interpretation of amphetamine concentration in blood samples from the perspective of direct or indirect cause of death.

  10. Concurrent use of amphetamine stimulants and antidepressants by undergraduate students

    Directory of Open Access Journals (Sweden)

    Vo K

    2015-01-01

    Full Text Available Kim Vo,1 Patricia J Neafsey,2 Carolyn A Lin3 1University of Connecticut Health Center, Farmington, 2School of Nursing and Center for Health Information and Prevention, University of Connecticut, Storrs, 3Department of Communication Sciences and Center for Health Information and Prevention, University of Connecticut, Storrs, CT, USA Abstract: Undergraduate students were recruited to participate in an online survey to report their use of amphetamine stimulants and other drugs. Significant differences were found between students reporting (n=79; 4.0% and not reporting (n=1,897; 96% amphetamine-stimulant use in the past month – in terms of race/ethnicity, class standing, residence, health symptoms, self-health report – in addition to alcohol, tobacco, pain-reliever, and antidepressant use. Health symptoms reported more often by stimulant users included depression, diarrhea, difficulty sleeping, fatigue, dizziness, difficulty concentrating, and nicotine craving. Health care providers of college students should query these patients about symptoms that could be related to depression and amphetamine use. In particular, they should provide education at the point of care around the risks of amphetamine use in general and the specific risks in those students who have symptoms of depression and/or are taking antidepressant medication. Prevention programs should also target the risks of concurrent use of amphetamines, antidepressants, and other drugs among college students. Keywords: stimulant use, depression, college students, self-medication

  11. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

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    Joshua L. Fenderson

    2013-01-01

    Full Text Available The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS. She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  12. Amphetamine positive urine toxicology screen secondary to atomoxetine.

    Science.gov (United States)

    Fenderson, Joshua L; Stratton, Amy N; Domingo, Jennifer S; Matthews, Gerald O; Tan, Christopher D

    2013-01-01

    The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS). She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.

  13. Attention performance among Brazilian truck drivers and its association with amphetamine use: pilot study

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    Lucio Garcia de Oliveira

    2013-10-01

    Full Text Available The aim of this article was to describe the attention functioning of twenty-two truck drivers and its relationship with amphetamine use. Those drivers who reported using amphetamines in the twelve months previous to the interview had the best performance in a test evaluating sustained attention functioning. Although amphetamine use may initially seem advantageous to the drivers, it may actually impair safe driving. The findings suggest the importance of monitoring the laws regarding amphetamine use in this country.

  14. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Amphetamine and methamphetamine inhalers regarded... DRUGS New Drug or Prescription Status of Specific Drugs § 250.101 Amphetamine and methamphetamine... and the methamphetamine they contain is being used as a substitute for amphetamine...

  15. Amphetamines, new psychoactive drugs and the monoamine transporter cycle.

    Science.gov (United States)

    Sitte, Harald H; Freissmuth, Michael

    2015-01-01

    In monoaminergic neurons, the vesicular transporters and the plasma membrane transporters operate in a relay. Amphetamine and its congeners target this relay to elicit their actions: most amphetamines are substrates, which pervert the relay to elicit efflux of monoamines into the synaptic cleft. However, some amphetamines act as transporter inhibitors. Both compound classes elicit profound psychostimulant effects, which render them liable to recreational abuse. Currently, a surge of new psychoactive substances occurs on a global scale. Chemists bypass drug bans by ingenuous structural variations, resulting in a rich pharmacology. A credible transport model must account for their distinct mode of action and link this to subtle differences in activity and undesired, potentially deleterious effects.

  16. Review article: amphetamines and related drugs of abuse.

    Science.gov (United States)

    Greene, Shaun L; Kerr, Fergus; Braitberg, George

    2008-10-01

    Acute amphetamine toxicity is a relatively common clinical scenario facing the Australasian emergency medicine physician. Rates of use in Australasia are amongst the highest in the world. Clinical effects are a consequence of peripheral and central adrenergic stimulation producing a sympathomimetic toxidrome and a spectrum of central nervous system effects. Assessment aims to detect the myriad of possible complications related to acute amphetamine exposure and to institute interventions to limit associated morbidity and mortality. Meticulous supportive care aided by judicial use of benzodiazepines forms the cornerstone of management. Beta blockers are contraindicated in managing cardiovascular complications. Agitation and hyperthermia must be treated aggressively. Discharge of non-admitted patients from the emergency department should only occur once physiological parameters and mental state have returned to normal. All patients should receive education regarding the dangers of amphetamine use.

  17. Bupropion interference with immunoassays for amphetamines and LSD.

    Science.gov (United States)

    Vidal, Christian; Skripuletz, Thomas

    2007-06-01

    A 50-year-old male patient suddenly had lost consciousness, although he had previously been healthy. On arrival at hospital seizures arose. The authors investigated a urine sample of the patient, and performed toxicological drug screening with immunochemical Cloned Enzyme Donor Immunoassay (CEDIA) assays. Positive findings for amphetamines and LSD could not be confirmed. Using gas chromatography/mass spectrometry (GC/MS), and liquid chromatography/mass spectrometry (LC/MS), the authors identified bupropion, a drug used to aid in smoking cessation, as the interfering compound, which may cause false-positive results for amphetamines and LSD using the CEDIA assays.

  18. Modulation of neuropeptide FF (NPFF) receptors influences the expression of amphetamine-induced conditioned place preference and amphetamine withdrawal anxiety-like behavior in rats.

    Science.gov (United States)

    Kotlinska, J H; Gibula-Bruzda, E; Koltunowska, D; Raoof, H; Suder, P; Silberring, J

    2012-01-01

    Many data indicate that endogenous opioid system is involved in amphetamine-induced behavior. Neuropeptide FF (NPFF) possesses opioid-modulating properties. The aim of the present study was to determine whether pharmacological modulation of NPFF receptors modify the expression of amphetamine-induced conditioned place preference (CPP) and amphetamine withdrawal anxiety-like behavior, both processes relevant to drug addiction/abuse. Intracerebroventricular (i.c.v.) injection of NPFF (5, 10, and 20 nmol) inhibited the expression of amphetamine CPP at the doses of 10 and 20 nmol. RF9, the NPFF receptors antagonist, reversed inhibitory effect of NPFF (20 nmol, i.c.v.) at the doses of 10 and 20 nmol and did not show any effect in amphetamine- and saline conditioned rats. Anxiety-like effect of amphetamine withdrawal was measured 24h after the last (14 days) amphetamine (2.5mg/kg, i.p.) treatment in the elevated plus-maze test. Amphetamine withdrawal decreased the percent of time spent by rats in the open arms and the percent of open arms entries. RF9 (5, 10, and 20 nmol, i.c.v.) significantly reversed these anxiety-like effects of amphetamine withdrawal and elevated the percent of time spent by rats in open arms at doses of 5 and 10 nmol, and the percent of open arms entries in all doses used. NPFF (20 nmol) pretreatment inhibited the effect of RF9 (10 nmol). Our results indicated that stimulation or inhibition of NPFF receptors decrease the expression of amphetamine CPP and amphetamine withdrawal anxiety, respectively. These findings may have implications for a better understanding of the processes involved in amphetamine dependence.

  19. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

    Kahlig, Kristopher M; Lute, Brandon J; Wei, Yuqiang

    2006-01-01

    The dopamine (DA) transporter (DAT) mediates the removal of released DA. DAT is the major molecular target responsible for the rewarding properties and abuse potential of the psychostimulant amphetamine (AMPH). AMPH has been shown to reduce the number of DATs at the cell surface, and this AMPH...

  20. Amphetamine Containing Dietary Supplements and Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Julio Perez-Downes

    2016-01-01

    Full Text Available Weight loss is one of the most researched and marketed topics in American society. Dietary regimens, medications that claim to boost the metabolism, and the constant pressure to fit into society all play a role in our patient’s choices regarding new dietary products. One of the products that are well known to suppress appetite and cause weight loss is amphetamines. While these medications suppress appetite, most people are not aware of the detrimental side effects of amphetamines, including hypertension, tachycardia, arrhythmias, and in certain instances acute myocardial infarction. Here we present the uncommon entity of an acute myocardial infarction due to chronic use of an amphetamine containing dietary supplement in conjunction with an exercise regimen. Our case brings to light further awareness regarding use of amphetamines. Clinicians should have a high index of suspicion of use of these substances when young patients with no risk factors for coronary artery disease present with acute arrhythmias, heart failure, and myocardial infarctions.

  1. The neurotoxicity of amphetamines during the adolescent period.

    Science.gov (United States)

    Teixeira-Gomes, Armanda; Costa, Vera Marisa; Feio-Azevedo, Rita; Bastos, Maria de Lourdes; Carvalho, Félix; Capela, João Paulo

    2015-04-01

    Amphetamine-type psychostimulants (ATS), such as amphetamine (AMPH), 3,4-methylenedioxymethamphetamine (MDMA), and methamphetamine (METH) are psychoactive substances widely abused, due to their powerful central nervous system (CNS) stimulation ability. Young people particularly use ATS as recreational drugs. Moreover, AMPH is used clinically, particularly for attention deficit hyperactivity disorder, and has the ability to cause structural and functional brain alterations. ATS are known to interact with monoamine transporter sites and easily diffuse across cellular membranes, attaining high levels in several tissues, particularly the brain. Strong evidence suggests that ATS induce neurotoxic effects, raising concerns about the consequences of drug abuse. Considering that many teenagers and young adults commonly use ATS, our main aim was to review the neurotoxic effects of amphetamines, namely AMPH, MDMA, and METH, in the adolescence period of experimental animals. Reports agree that adolescent animals are less susceptible than adult animals to the neurotoxic effects of amphetamines. The susceptibility to the neurotoxic effects of ATS seems roughly located in the early adolescent period of animals. Many authors report that the age of exposure to ATS is crucial for the neurotoxic outcome, showing that the stage of brain maturity has a strong importance. Moreover, recent studies have been undertaken in young adults and/or consumers during adolescence that clearly indicate brain or behavioural damage, arguing for long-term neurotoxic effects in humans. There is an urgent need for more studies during the adolescence period, in order to unveil the mechanisms and the brain dysfunctions promoted by ATS.

  2. ANN expert system screening for illicit amphetamines using molecular descriptors

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.

    2007-05-01

    The goal of this study was to develop and an artificial neural network (ANN) based on computed descriptors, which would be able to classify the molecular structures of potential illicit amphetamines and to derive their biological activity according to the similarity of their molecular structure with amphetamines of known toxicity. The system is necessary for testing new molecular structures for epidemiological, clinical, and forensic purposes. It was built using a database formed by 146 compounds representing drugs of abuse (mainly central stimulants, hallucinogens, sympathomimetic amines, narcotics and other potent analgesics), precursors, or derivatized counterparts. Their molecular structures were characterized by computing three types of descriptors: 38 constitutional descriptors (CDs), 69 topological descriptors (TDs) and 160 3D-MoRSE descriptors (3DDs). An ANN system was built for each category of variables. All three networks (CD-NN, TD-NN and 3DD-NN) were trained to distinguish between stimulant amphetamines, hallucinogenic amphetamines, and nonamphetamines. A selection of variables was performed when necessary. The efficiency with which each network identifies the class identity of an unknown sample was evaluated by calculating several figures of merit. The results of the comparative analysis are presented.

  3. Amphetamines modulate prefrontal γ oscillations during attention processing.

    Science.gov (United States)

    Franzen, John D; Wilson, Tony W

    2012-08-22

    Amphetamine-based medications robustly suppress symptoms of attention-deficit/hyperactivity disorder (ADHD), but their exact mechanisms remain poorly understood. Recent hemodynamic imaging studies have suggested that amphetamines may modulate the prefrontal and anterior cingulate brain regions, although few studies have been published and the results have not been entirely consistent. Meanwhile, several electrophysiological studies have shown that abnormal fast oscillations (in the γ range) may be closely linked to inattention and other cardinal symptoms of ADHD. In this study, we utilized magnetoencephalography to examine how amphetamines modulate high-frequency brain activity in adults with ADHD. Participants performed an auditory attention task, which required sustained attention in one block and passive listening in a separate block. Participants completed the task twice in the on-medication and off-medication states. All data were analyzed using beamforming techniques to resolve cortical regions showing event-related synchronizations and desynchronizations. Our primary findings indicated that oral administration of amphetamine decreased γ-band event-related desynchronization activity significantly in the medial prefrontal area and decreased event-related synchronization in bilateral superior parietal areas, left inferior parietal, and the left inferior frontal gyrus. These results suggest that psychostimulants strongly modulate γ activity in frontal and parietal cortical areas, which are known to be central to the brain's core attentional networks.

  4. Cardiovascular Complications of Acute Amphetamine Abuse; Cross-sectional study

    Directory of Open Access Journals (Sweden)

    Elham Bazmi

    2017-03-01

    Full Text Available Objectives: This study aimed to evaluate cardiovascular complications among patients who abuse amphetamines. Methods: This cross-sectional study took place between April 2014 and April 2015 among 3,870 patients referred to the Toxicology Emergency Department of Baharlou Hospital, Tehran University of Medical Sciences, Tehran, Iran. Those with clinical signs of drug abuse and positive urine screening tests were included in the study, while cases of chronic abuse were excluded. Cardiac complications were evaluated via electrocardiography (ECG and transthoracic echocardiography. Results: A total of 230 patients (5.9% had a history of acute amphetamine abuse and positive urine tests. Of these, 32 patients (13.9% were <20 years old and 196 (85.2% were male. In total, 119 (51.7% used amphetamine and methamphetamine compounds while 111 (48.3% used amphetamines with morphine or benzodiazepines. The most common ECG finding was sinus tachycardia (43.0%, followed by sinus tachycardia plus a prolonged QT interval (34.3%. Mean creatine kinase-MB and troponin I levels were 35.9 ± 4.3 U/mL and 0.6 ± 0.2 ng/mL, respectively. A total of 60 patients (26.1% were admitted to the Intensive Care Unit. The majority (83.3% of these patients had normal echocardiography results. The mean aortic root diameter (ARD was 27.2 ± 2.8 mm. Abnormalities related to the ARD were found in 10 patients (16.7%, three of whom subsequently died. Conclusion: According to these findings, cardiac complications were common among Iranian patients who abuse amphetamines, although the majority of patients had normal echocardiography and ECG findings.

  5. Physiological and behavioral effects of amphetamine in BACE1(-/-) mice.

    Science.gov (United States)

    Paredes, R Madelaine; Piccart, E; Navaira, E; Cruz, D; Javors, M A; Koek, W; Beckstead, M J; Walss-Bass, C

    2015-06-01

    β-Site APP-cleaving Enzyme 1 (BACE1) is a protease that has been linked to schizophrenia, a severe mental illness that is potentially characterized by enhanced dopamine (DA) release in the striatum. Here, we used acute amphetamine administration to stimulate neuronal activity and investigated the neurophysiological and locomotor-activity response in BACE1-deficient (BACE1(-/-) ) mice. We measured locomotor activity at baseline and after treatment with amphetamine (3.2 and 10 mg/kg). While baseline locomotor activity did not vary between groups, BACE1(-/-) mice exhibited reduced sensitivity to the locomotor-enhancing effects of amphetamine. Using high-performance liquid chromatography (HPLC) to measure DA and DA metabolites in the striatum, we found no significant differences in BACE1(-/-) compared with wild-type mice. To determine if DA neuron excitability is altered in BACE1(-/-) mice, we performed patch-clamp electrophysiology in putative DA neurons from brain slices that contained the substantia nigra. Pacemaker firing rate was slightly increased in slices from BACE1(-/-) mice. We next measured G protein-coupled potassium currents produced by activation of D2 autoreceptors, which strongly inhibit firing of these neurons. The maximal amplitude and decay times of D2 autoreceptor currents were not altered in BACE1(-/-) mice, indicating no change in D2 autoreceptor-sensitivity and DA transporter-mediated reuptake. However, amphetamine (30 µm)-induced potassium currents produced by efflux of DA were enhanced in BACE1(-/-) mice, perhaps indicating increased vesicular DA content in the midbrain. This suggests a plausible mechanism to explain the decreased sensitivity to amphetamine-induced locomotion, and provides evidence that decreased availability of BACE1 can produce persistent adaptations in the dopaminergic system.

  6. Class identity assignment for amphetamines using neural networks and GC-FTIR data

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Van Bocxlaer, J.; De Leenheer, A. P.; Massart, D. L.

    2006-08-01

    An exploratory analysis was performed in order to evaluate the feasibility of building of neural network (NN) systems automating the identification of amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical and forensic purposes. A first neural network system was built to distinguish between amphetamines and nonamphetamines. A second, more refined system, aimed to the recognition of amphetamines according to their toxicological activity (stimulant amphetamines, hallucinogenic amphetamines, nonamphetamines). Both systems proved that discrimination between amphetamines and nonamphetamines, as well as between stimulants, hallucinogens and nonamphetamines is possible (83.44% and 85.71% correct classification rate, respectively). The spectroscopic interpretation of the 40 most important input variables (GC-FTIR absorption intensities) shows that the modeling power of an input variable seems to be correlated with the stability and not with the intensity of the spectral interaction. Thus, discarding variables only because they correspond to spectral windows with weak absorptions does not seem be not advisable.

  7. Dexamethasone mimicks the antimotion sickness effects of amphetamine and scopolamine

    Science.gov (United States)

    Kohl, Randall Lee

    Based on preliminary suggestions that individual differences in susceptibility to stressful motion might be related to physiological differences in responses of the hypothalamic-pituitary-adrenal axis, we tested the efficacy of dexamethasone and metyrapone in subjects exposed to cross-coupled accelerative semicircular canal stimulation on a rotating chair. Subjects given 0.5 mg of dexamethasone every 6 h for 48 h could endure 80% more stressful motion ( P = 0.03) in a within-subjects design study, whereas, no improvement followed treatment with 750 mg of metryapone every 4 h for 24 h. The efficacy of dexamethasone might be explained in terms of its neurochemical actions on several neurotransmitter systems which are also modulated by such classical antimotion sickness drugs as amphetamine and scopolamine. Because dexamethasone induces adaptive changes within the central nervous system it may prove superior to scopolamine and amphetamine which possess significant side effects, are short acting, and rapidly tolerated.

  8. The Basal Ganglia as a Substrate for the Multiple Actions of Amphetamines

    OpenAIRE

    Natarajan, Reka; Yamamoto, Bryan K.

    2011-01-01

    Amphetamines are psychostimulant drugs with high abuse potential. Acute and chronic doses of amphetamines affect dopamine (DA) neurotransmission in the basal ganglia. The basal ganglia are a group of subcortical nuclei that are anatomically positioned to integrate cognitive, motor and sensorimotor inputs from the cortex. Amphetamines can differentially alter the functioning of specific BG circuits to produce neurochemical changes that affect cognition, movement, and drug seeking behavior thro...

  9. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    OpenAIRE

    Fenderson, Joshua L.; Stratton, Amy N; Domingo, Jennifer S.; Matthews, Gerald O.; Tan, Christopher D.

    2013-01-01

    The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substan...

  10. Misdiagnosed Pruritus; Formication due to Chronic Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Maryam Vahabzadeh

    2016-03-01

    Full Text Available Amphetamine abusers are shown to have significant cognitive impairments as well as delusional disorders. We present a 17-year-old man who was admitted to the toxicology emergency department with amphetamine overdose. Along with the classic signs and symptoms of overdose including mydriasis, tachycardia, hypertension, sweating and severe agitation, his urine toxicology screen test was found to be positive for 3,4-methylenedioxy-methamphetamine. In physical examination, widespread round-to-oval cutaneous lesions were observed all over his limbs and chest, notably the most easily reached sites of skin to be scratched. After regaining consciousness, the patient complained of pruritus and sensing the movement of insects under his skin. Further medical history showed that he had abused amphetamines for more than two years along with persistent pruritus, for which he had visited different physicians who mainly had made the diagnosis of allergy or dermatitis for him. He had been treated with antihistamines (hydroxyzine for a long period. He also had been diagnosed with scabies and treated with topical permethrin and lindane lotion. Despite receiving these treatments, he continued to have pruritus particularly on his forearms and hands. He was finally diagnosed with “Ekbom’s syndrome” and referred to psychological rehabilitation and psychosomatic outpatient clinic.

  11. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis

    Directory of Open Access Journals (Sweden)

    Natalia M. Branis

    2015-01-01

    Full Text Available Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35–7.45, bicarbonate 16 mmol/L (22–29 mmol/L, and anion gap 19 mmol/L (8–16 mmol/L. Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  12. Amphetamine-Like Analogues in Diabetes: Speeding towards Ketogenesis.

    Science.gov (United States)

    Branis, Natalia M; Wittlin, Steven D

    2015-01-01

    Obesity is common in patients with type 1 and type 2 diabetes. Amphetamine-like analogues comprise the most popular class of weight loss medications. We present a case of a 34-year-old African American female with a history of type 1 diabetes, dyslipidemia, and obesity who developed diabetic ketoacidosis (DKA) after starting Diethylpropion for the purpose of weight loss. Shortly after starting Diethylpropion, she developed nausea, vomiting, and periumbilical pain. Blood work revealed glucose of 718 mg/dL, pH 7.32 (7.35-7.45), bicarbonate 16 mmol/L (22-29 mmol/L), and anion gap 19 mmol/L (8-16 mmol/L). Urine analysis demonstrated large amount of ketones. She was hospitalized and successfully treated for DKA. Diethylpropion was discontinued. Amphetamine-like analogues administration leads to norepinephrine release from the lateral hypothalamus which results in the appetite suppression. Peripheral norepinephrine concentration rises as well. Norepinephrine stimulates adipocyte lipolysis and thereby increases nonesterified fatty acids (NEFA) availability. It promotes β-oxidation of NEFA to ketone bodies while decreasing metabolic clearance rate of ketones. In the setting of acute insulin deficiency these effects are augmented. Females are more sensitive to norepinephrine effects compared to males. In conclusion, amphetamine-like analogues lead to a release of norepinephrine which can result in a clinically significant ketosis, especially in the setting of insulin deficiency.

  13. Amphetamine-induced psychosis - a separate diagnostic entity or primary psychosis triggered in the vulnerable?

    Directory of Open Access Journals (Sweden)

    Bramness Jørgen G

    2012-12-01

    Full Text Available Abstract Use of amphetamine and methamphetamine is widespread in the general population and common among patients with psychiatric disorders. Amphetamines may induce symptoms of psychosis very similar to those of acute schizophrenia spectrum psychosis. This has been an argument for using amphetamine-induced psychosis as a model for primary psychotic disorders. To distinguish the two types of psychosis on the basis of acute symptoms is difficult. However, acute psychosis induced by amphetamines seems to have a faster recovery and appears to resolve more completely compared to schizophrenic psychosis. The increased vulnerability for acute amphetamine induced psychosis seen among those with schizophrenia, schizotypal personality and, to a certain degree other psychiatric disorders, is also shared by non-psychiatric individuals who previously have experienced amphetamine-induced psychosis. Schizophrenia spectrum disorder and amphetamine-induced psychosis are further linked together by the finding of several susceptibility genes common to both conditions. These genes probably lower the threshold for becoming psychotic and increase the risk for a poorer clinical course of the disease. The complex relationship between amphetamine use and psychosis has received much attention but is still not adequately explored. Our paper reviews the literature in this field and proposes a stress-vulnerability model for understanding the relationship between amphetamine use and psychosis.

  14. Risk factors of schizophrenia development in patients with amphetamines dependence and psychosis (amphetamine-induced psychosis and schizophrenia, and without psychosis [Czynniki ryzyka rozwoju schizofrenii u pacjentów uzależnionych od amfetaminy i jej pochodnych z psychozą (pointoksykacyjną lub schizofrenią oraz bez psychozy

    Directory of Open Access Journals (Sweden)

    Rabe-Jabłońska, Jolanta

    2012-08-01

    Full Text Available Aim. Amphetamine and its derivates can induce, usually after many intoxications, schizophrenia-like psychosis. These disorders appeared only in part patients with amphetamine dependence. Aim of the study was to establish prevalence of selective risk factors of schizophrenia development in amphetamine users: 1 with amphetamine – induced schizophrenia – like psychosis, 2 with schizophrenia, and 2 without psychotic symptoms. Material. In the study 3 groups of subjects were included: 30 amphetamine users with amphetamine induced schizophrenia – like psychosis, 30 amphetamine users with schizophrenia and 30 amphetamine users without psychotic symptoms (37 female and 53 male in mean age=17.78 years . Methods. Amphetamine dependence, schizophrenia and schizophrenia-like psychosis induced amphetamine were diagnosed according to ICD-10 criteria after at least 1 year of amphetamine abstinence. The next procedure was used: 1 Structured interview with subjects and their mothers/caregivers regarding: a amphetamines use (duration of abuse, doses of psychoactive substance b family history of psychosis (especially schizophrenia 2 The Questionnaire of Child Development for assessment of prevalence of selected risk factors of schizophrenia development 3 The Premorbid Adjustment Scale (Cannon – Spoor for assessment of premorbid psychosocial functioning in thelast year before psychosis. Conclusions. Amphetamines users with amphetamine-induced psychosis were more similar in prevalence of selective risk factors of schizophrenia development to subjects with schizophrenia and amphetamine dependence than to amphetamine users without psychosis. Amphetamine-induced psychosis developed more frequently in amphetamine users who used higher amphetamine doses and with familial history of psychosis.

  15. Effects of Amphetamine and β-Endorphin Fragments on Maze Performance in Rats

    NARCIS (Netherlands)

    Boer, S. de; Bohus, B.

    1990-01-01

    Fragments of β-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two β-endorphin fragments [β-endorphin (βE)-(2-9) and βE-(2-16)] on maze behavior in more detail. In Experiment I no significant

  16. Effects of amphetamine and beta-endorphin fragments on maze performance in rats

    NARCIS (Netherlands)

    Bohus, B; de Boer, S.F.

    1990-01-01

    Fragments of beta-endorphin and amphetamine cause similar effects in some tests of maze behavior in rats. The present study served to compare the influence of amphetamine and two beta-endorphin fragments [beta-endorphin (beta E)-(2-9) and beta E-(2-16)] on maze behavior in more detail. In Experiment

  17. Ab Initio Calculations and Raman and SERS Spectral Analyses of Amphetamine Species

    DEFF Research Database (Denmark)

    Berg, Rolf W.; Nørbygaard, Thomas; White, Peter C.

    2011-01-01

    . The spectra of amphetamine and amphetamine-H+ sampleswere obtained and assigned according to a comparison of the experimental spectra and the ab initio MO calculations, performed using the Gaussian 03W program (Gaussian, Inc., Pittsburgh, PA). The analyses were based on complete geometry minimization...

  18. 49 CFR 40.137 - On what basis does the MRO verify test results involving marijuana, cocaine, amphetamines, or PCP?

    Science.gov (United States)

    2010-10-01

    ... involving marijuana, cocaine, amphetamines, or PCP? 40.137 Section 40.137 Transportation Office of the... results involving marijuana, cocaine, amphetamines, or PCP? (a) As the MRO, you must verify a confirmed positive test result for marijuana, cocaine, amphetamines, and/or PCP unless the employee presents...

  19. 75 FR 69088 - Determination That Amphetamine Sulfate, 5 and 10 Milligram Tablets, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2010-11-10

    ... HUMAN SERVICES Food and Drug Administration Determination That Amphetamine Sulfate, 5 and 10 Milligram... Amphetamine sulfate, 5 and 10 milligram (mg) tablets, was not withdrawn from sale for reasons of safety or... Amphetamine sulfate, 5 mg and 10 mg tablets, if all other legal and regulatory requirements are met....

  20. The pharmacology and clinical outcomes of amphetamines to treat ADHD: does composition matter?

    Science.gov (United States)

    Hodgkins, Paul; Shaw, Monica; McCarthy, Suzanne; Sallee, Floyd R

    2012-03-01

    Attention-deficit hyperactivity disorder (ADHD) treatment options include pharmacological and nonpharmacological approaches. In North America, psychostimulants (amphetamine and methylphenidate) are considered first-line pharmacological treatments for patients (children, adolescents and adults) with ADHD. However, in the UK, National Institute for Health and Clinical Excellence (NICE) guidelines have placed short-acting d-amphetamine as a third-line treatment option due to a lack of contemporary, published clinical trials on its efficacy and the concerns from clinical and patient experts regarding the potential for increased abuse and/or misuse compared with methylphenidate. These guidelines do not account for some of the more recent amphetamine products that have been developed to alleviate some of these concerns, but that are not currently approved in the UK or other European countries. The purpose of this review is to describe the pharmacology and clinical efficacy of various amphetamine compositions, as well as to explore the apparent differences in these compositions and their associated risks and benefits. A PubMed literature search was conducted to investigate amphetamine pharmacology, clinical efficacy and safety and ADHD outcomes in the published literature from 1980 through March 2011. Search terms included the keywords 'ADHD' or 'ADD' or 'hyperkinetic disorder' and any of the following keywords combined with 'or': 'amphetamine', 'dexamphetamine', 'mixed amphetamine salts', 'lisdexamfetamine' and 'methamphetamine'. The search included English-language primary research articles and review articles but excluded editorial articles and commentaries. The literature search resulted in 330 articles. Pertinent articles relating to amphetamine pharmacology, compositions, clinical efficacy and safety, effectiveness and tolerability, ADHD outcomes and abuse liability were included in this review. The different delivery profiles of amphetamine compositions result in

  1. Acute Demyelination in a Person with Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Serge Weis

    2011-01-01

    Full Text Available We report the case of a 31-year-old woman, admitted to the hospital for chest pain, dying a few days later from septic multiorgan failure, and showing at autopsy foci of acute demyelination in the occipital lobe. Gas chromatography/mass spectrometry analysis revealed the presence of amphetamine in the demyelinated area, which might be considered as the pathogenic agent, since other causes for demyelination could be excluded. This case represents the first report showing a demyelinating process due to a street drug.

  2. Dimethylamylamine: a drug causing positive immunoassay results for amphetamines.

    Science.gov (United States)

    Vorce, Shawn P; Holler, Justin M; Cawrse, Brian M; Magluilo, Joseph

    2011-04-01

    The Department of Defense (DoD) operates six forensic urine drug-testing laboratories that screen close to 5 million urine samples for amphetamines yearly. Recently, the DoD laboratories have observed a significant decrease in the confirmation rates for amphetamines because of specimens screening positive by two separate immunoassays and confirming negative by gas chromatography-mass spectrometry (GC-MS). Previous studies conducted by the Division of Forensic Toxicology, Armed Force Institute of Pathology (AFIP) utilizing a GC-MS basic drug screen and a designer drug screen revealed no common compound or compound classes as to the cause of the immunoassay-positive results. Additional information obtained from an immunoassay vendor suggested the anorectic compound dimethylamylamine (DMAA) may be the cause of the false-positive screens. An additional 134 false-positive samples were received and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for DMAA. LC-MS-MS analysis revealed the presence of DMAA in 92.3% of the false-positive samples at a concentration of approximately 6.0 mg/L DMAA, causing a positive screen on both immunoassay kits.

  3. Miniaturized sample preparation method for determination of amphetamines in urine.

    Science.gov (United States)

    Nishida, Manami; Namera, Akira; Yashiki, Mikio; Kimura, Kojiro

    2004-07-16

    A simple and miniaturized sample preparation method for determination of amphetamines in urine was developed using on-column derivatization and gas chromatography-mass spectrometry (GC-MS). Urine was directly applied to the extraction column that was pre-packed with Extrelut and sodium carbonate. Amphetamine (AP) and methamphetamine (MA) in urine were adsorbed on the surface of Extrelut. AP and MA were then converted to a free base and derivatized to N-propoxycarbonyl derivatives using propylchloroformate on the column. Pentadeuterated MA was used as an internal standard. The recoveries of AP and MA from urine were 100 and 102%, respectively. The calibration curves showed linearity in the range of 0.50-50 microg/mL for AP and MA in urine. When urine samples containing two different concentrations (0.50 and 5.0 microg/mL) of AP and MA were determined, the intra-day and inter-day coefficients of variation were 1.4-7.7%. This method was applied to 14 medico-legal cases of MA intoxication. The results were compared and a good agreement was obtained with a HPLC method.

  4. The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results.

    Science.gov (United States)

    Baron, Jason M; Griggs, David A; Nixon, Andrea L; Long, William H; Flood, James G

    2011-07-01

    Amphetamines and methamphetamines are part of an important class of drugs included in most urine drugs of abuse screening panels, and a common assay to detect these drugs is the Amphetamines II immunoassay (Roche Diagnostics). To demonstrate that meta-chlorophenylpiperazine (m-CPP), a trazodone metabolite, cross-reacts in the Amphetamines II assay, we tested reference standards of m-CPP at various concentrations (200 to 20,000 g/L). We also tested real patient urine samples containing m-CPP (detected and quantified by HPLC) with no detectable amphetamine, methamphetamine, or MDMA (demonstrated by GC MS). In both the m-CPP standards and the patient urine samples, we found a strong association between m-CPP concentration and Amphetamines II immunoreactivity (r = 0.990 for the urine samples). Further, we found that patients taking trazodone can produce urine with sufficient m-CPP to result in false-positive Amphetamines II results. At our institution, false-positive amphetamine results occur not infrequently in patients taking trazodone with at least 8 trazodone-associated false-positive results during a single 26-day period. Laboratories should remain cognizant of this interference when interpreting results of this assay.

  5. Studies on the metabolism and the detectability of 4-methyl-amphetamine and its isomers 2-methyl-amphetamine and 3-methyl-amphetamine in rat urine using GC-MS and LC-(high-resolution)-MSn.

    Science.gov (United States)

    Welter, Jessica; Meyer, Markus R; Kavanagh, Pierce; Maurer, Hans H

    2014-03-01

    4-Methyl-amphetamine (1-(4-methylphenyl)propane-2-amine; 4-MA) and its isomers 2-methyl-amphetamine (2-MA) and 3-methyl-amphetamine (3-MA) belong to the group of amphetamine-type stimulants and of new psychoactive substances. Several studies showed similar potencies in releasing noradrenalin and dopamine, but higher potencies in releasing serotonin than amphetamine. In March 2013, the EU Council decided on an EU-wide control based on the European Monitoring Centre for Drugs and Drug Addiction risk assessment report documenting that 4-MA was sold as amphetamine on the illicit market and detected in several fatal cases. Therefore, 4-MA and its isomers should be covered by drug testing in clinical and forensic toxicology. The aims of the presented work were to study the metabolism and detectability of each isomer in urine samples. For metabolism studies, rat urine samples were isolated by solid-phase extraction without and after enzymatic cleavage of conjugates. The phase I metabolites were separated and identified after acetylation by gas chromatography-mass spectrometry (GC-MS) and/or liquid chromatography-high resolution-linear ion trap mass spectrometry (LC-HR-MS(n)) and the phase II metabolites by LC-HR-MS(n). From the identified phase I and II metabolites, the following main metabolic pathways were deduced: aromatic hydroxylation, hydroxylation of the phenylmethyl group followed by oxidation to the corresponding carboxylic acid, hydroxylation of the side chain, and glucuronidation and/or sulfation of the hydroxy and carboxy groups. CYP2D6 was involved in the aromatic hydroxylation. Finally, the intake of a commonly used dose of the MAs could be confirmed in rat urine using the authors' GC-MS and the LC-MS(n) standard urine screening approaches. Differentiation of the isomers to confirm the intake of a specific isomer was possible with an additional workup in rat urine.

  6. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    Institute of Scientific and Technical Information of China (English)

    SUN Jin-Hai; SHEN Jing-Ling; LIANG Lai-Shun; XU Xiao-Yu; LIU Hai-Bo; ZHANG Cun-Lin

    2005-01-01

    @@ The spectral absorption features of three amphetamine-type stimulants (ATS) belonging to illicit drugs have been studied with terahertz (THz) time-domain spectroscopy (THz-TDS) and the characteristic absorption spectra (fingerprint spectra) are obtained in the range from 0.2 to 2.5 THz. Fingerprint spectra of illicit drugs in terahertz band are bases to detect and to inspect nondestructively illicit drugs with terahertz technique. With fingerprint spectra of illicit drugs and strong penetrability for cloths, paper bags and leathered or plastic luggage terahertz technique would be better than other techniques in illicit drugs detection and inspection. Thus, this work would contribute to the building of corresponding fingerprint spectra database of illicit drugs and provide experimental bases for using of terahertz detection apparatus in drugs nondestructive detection and inspection in the future.

  7. PI3K signaling supports amphetamine-induced dopamine efflux.

    Science.gov (United States)

    Lute, Brandon J; Khoshbouei, Habibeh; Saunders, Christine; Sen, Namita; Lin, Richard Z; Javitch, Jonathan A; Galli, Aurelio

    2008-08-01

    The dopamine (DA) transporter (DAT) is a major molecular target of the psychostimulant amphetamine (AMPH). AMPH, as a result of its ability to reverse DAT-mediated inward transport of DA, induces DA efflux thereby increasing extracellular DA levels. This increase is thought to underlie the behavioral effects of AMPH. We have demonstrated previously that insulin, through phosphatidylinositol 3-kinase (PI3K) signaling, regulates DA clearance by fine-tuning DAT plasma membrane expression. PI3K signaling may represent a novel mechanism for regulating DA efflux evoked by AMPH, since only active DAT at the plasma membrane can efflux DA. Here, we show in both a heterologous expression system and DA neurons that inhibition of PI3K decreases DAT cell surface expression and, as a consequence, AMPH-induced DA efflux.

  8. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    Science.gov (United States)

    Sun, Jin-Hai; Shen, Jing-Ling; Liang, Lai-Shun; Xu, Xiao-Yu; Liu, Hai-Bo; Zhang, Cun-Lin

    2005-12-01

    The spectral absorption features of three amphetamine-type stimulants (ATS) belonging to illicit drugs have been studied with terahertz (THz) time-domain spectroscopy (THz-TDS) and the characteristic absorption spectra (fingerprint spectra) are obtained in the range from 0.2 to 2.5 THz. Fingerprint spectra of illicit drugs in terahertz band are bases to detect and to inspect nondestructively illicit drugs with terahertz technique. With fingerprint spectra of illicit drugs and strong penetrability for cloths, paper bags and leathered or plastic luggage terahertz technique would be better than other techniques in illicit drugs detection and inspection. Thus, this work would contribute to the building of corresponding fingerprint spectra database of illicit drugs and provide experimental bases for using of terahertz detection apparatus in drugs nondestructive detection and inspection in the future.

  9. The shapes of neurotransmitters by millimetrewave spectroscopy: amphetamine

    Science.gov (United States)

    Godfrey, Peter D.; McGlone, Shane J.; Brown, Ronald D.

    2001-12-01

    We have studied the amphetamine molecule both experimentally by rotational spectroscopy and theoretically by ab initio molecular orbital calculations at the MP2/6-31G(d,p) level. Two species x and y of amphetamine detected by millimetre wave argon free jet expansion spectroscopy are identifiable from values of their rotational constants together with the quadrupole hyperfine patterns of some spectral lines. The more abundant conformer x is amp(1) and the less abundant y is amp(2) corresponding to the theoretical conformers I and II [see Fig. 2]. The identity of conformer x as amp(1) is supported by amino-hydrogen coordinate data obtained from detection of the N-deutero isotopomer of this conformer. Both amp(1) and amp(2) appear to be stabilized by non-classical hydrogen bonds from an amino hydrogen to the aromatic π-electron cloud, and have the methyl group trans to the phenyl substituent. Calculations of the relative energies of the conformers at the MP2/6-31 G(d,p) level suggest that the corresponding gauche-methyl conformers V and VI may be of energy similar to II. However, calculations of details of the potential energy surface at levels of theory higher than that used in the present work will be needed to clarify this question. By analogy with smaller disubstituted ethanes, we would expect the barriers to rotation about the C-C bond to be too high to enable relaxation of one conformer to another during the jet expansion.

  10. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit

    2014-01-01

    Addiction to psychostimulants (ie, amphetamines and cocaine) imposes a major socioeconomic burden. Prevention and treatment represent unmet medical needs, which may be addressed, if the mechanisms underlying psychostimulant action are understood. Cocaine acts as a blocker at the transporters...

  11. Differential Effect of Amphetamine Optical Isomers on Bender Gestalt Performance of the Minimally Brain Dysfunctioned

    Science.gov (United States)

    Arnold, L. Eugene; And Others

    1978-01-01

    The differential effect of amphetamine optical isomers on Bender Gestalt performance was examined in 31 hyperkinetic minimally brain dysfunctioned children between the ages of 4 and 12 years, using a double-blind Latin-square crossover comparison. (Author)

  12. The N terminus of monoamine transporters is a lever required for the action of amphetamines

    DEFF Research Database (Denmark)

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara;

    2010-01-01

    The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N...... terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERT(T81A) and SERT(T81D), suggested......, SERT(T81A) (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERT(T81A) were comparable with those through the wild type transporter. Both abundant Na...

  13. Comparative Cardiac Risks of Methylphenidate and Amphetamines in Treatment of ADHD

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

    Full Text Available The risk for adverse cardiac events in subjects between 3 and 20 years of age treated with methylphenidate or amphetamine salts for ADHD was determined in a retrospective study at University of Florida, Gainesville, FL.

  14. Antipsychotic pathway genes with expression altered in opposite direction by antipsychotics and amphetamine.

    Science.gov (United States)

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

    To develop a new strategy for identifying possible psychotic- or antipsychotic-related pathway genes, rats were treated with clinical doses of haloperidol and clozapine for 4 days, and the altered expression of genes was compared with the genes altered in expression after amphetamine sensitization. The objective was to identify genes with expression altered in the same direction by haloperidol and clozapine but in the opposite direction in the amphetamine-sensitized rat striatum. These criteria were met by 21 genes, consisting of 15 genes upregulated by amphetamine, and 6 genes downregulated by amphetamine. Of the 21 genes, 15 are not presently identified, and only 3 genes (cathepsin K, GRK6, and a gene with accession number AI177589) are located in chromosome regions known to be associated with schizophrenia.

  15. Stimulant therapy in the management of ADHD: mixed amphetamine salts (extended release).

    Science.gov (United States)

    Faraone, Stephen V

    2007-09-01

    The efficacy of amphetamines in the management of attention-deficit/hyperactivity disorder (ADHD) is well established. However, their value in improving the symptoms of ADHD has been compromised by concerns about compliance, abuse potential and adverse events. An extended-release formulation of mixed amphetamine salts (MAS XR) provided the first long-acting amphetamine formulation, and thus, filled an important gap in available treatments for ADHD. MAS XR has been shown to improve ADHD symptoms in children, adolescents and adults in both short- and long-term studies. The drug is generally well tolerated in clinical trials. Although its safety profile in patients with concomitant cardiovascular conditions in a real-world setting has yet to be fully evaluated, a tolerability study of mixed amphetamine salts in adults with ADHD who were being treated for primary essential hypertension showed that these patients can be safely treated with MAS XR.

  16. A single social defeat induces short-lasting behavioral sensitization to amphetamine

    NARCIS (Netherlands)

    de Jong, JG; Wasilewski, M; van der Vegt, BJ; Buwalda, B; Koolhaas, Jacob

    2005-01-01

    Repeated, intermittent exposure to psychostimulants or stressors results in long-lasting, progressive sensitization of the behavioral effects of a subsequent amphetamine (AMPH) challenge. Although behavioral sensitization has also been observed following a single drug pretreatment, the sensitizing p

  17. Use of amphetamines to improve the academic performance in students of the University of Manizales, 2008

    OpenAIRE

    Acevedo Urrego, Marcela; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Arango Orozco, Lisa; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Blandón Montoya, Liliana; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Buelvas Soto, Liz; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Carmona Velasquez, Daybeth Vanesa; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Castaño Castrillón, Jose Jaime; Profesor Titular, Director Centro de Investigaciones, Facultad de Medicina, Universidad de Manizales. Cra 9 # 19-03, Manizales, Caldas, Colombia. Correo electrónico .; Castro Rocha, Betsy Carolina; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Serna, Juan Camilo; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Trujillo Sandoval, Karol Susana; Estudiante 10° S emestre, Facultad de Medicina, Universidad de Manizales.; Arango, César; Docente Pediatría Facultad de Medicina, Universidad de Manizales Remitido para publicación: 16-02-2009. Aprobado para publicación: 11-03-2009

    2009-01-01

    Objective: Identify the frequency of use of non-medicated amphetamines and othersubstances to improve academic performance in students of the University of Manizales(Manizales, Colombia).Materials and methods: A cross sectional study was realized. The population was of3616 students of all the faculties of the University of Manizales, with a representativesample of 309 students. An anonymous sur5vey was made in order to collect informationwhich allowed to identify the consumption of amphetamin...

  18. Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

    Science.gov (United States)

    Kaplan, Justin; Shah, Pooja; Faley, Brian; Siegel, Mark E

    2015-12-01

    Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications. The literature contains reports of false-positive amphetamine UDSs with multiple antidepressants and antipsychotics. We present 2 cases of presumed false-positive UDSs for amphetamines after ingestion of aripiprazole. Case 1 was a 16-month-old girl who accidently ingested 15 to 45 mg of aripiprazole. She was lethargic and ataxic at home with 1 episode of vomiting containing no identifiable tablets. She remained sluggish with periods of irritability and was admitted for observation. UDS on 2 consecutive days came back positive for amphetamines. Case 2 was of a 20-month-old girl who was brought into the hospital after accidental ingestion of an unknown quantity of her father's medications which included aripiprazole. UDS on the first day of admission came back positive only for amphetamines. Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) on the blood and urine samples were also performed for both patients on presentation to detect amphetamines and were subsequently negative. Both patients returned to baseline and were discharged from the hospital. To our knowledge, these cases represent the first reports of false-positive amphetamine urine drug tests with aripiprazole. In both cases, aripiprazole was the drug with the highest likelihood of causing the positive amphetamine screen. The implications of these false-positives include the possibility of unnecessary treatment and monitoring of patients.

  19. Frequency of False Positive Amphetamine Screens due to Bupropion Using the Syva Emit II Immunoassay

    OpenAIRE

    Casey, Erica R; Scott, Mitchell G.; Tang, Schirin; Mullins, Michael E.

    2010-01-01

    Bupropion is a commonly prescribed, monocyclic antidepressant often used as an aid for smoking cessation. Several case reports have described false positive amphetamine urine drug screens (UDS) associated with bupropion. We sought to determine whether false positive amphetamine UDS due to the use of bupropion would be a frequent occurrence. We conducted an IRB-approved, retrospective chart review of all emergency department patients who underwent UDS between 1 January 2006 and 31 July 2007. A...

  20. Methamphetamine and Amphetamine Isomer Concentrations in Human Urine Following Controlled Vicks VapoInhaler Administration

    OpenAIRE

    Smith, Michael L.; Nichols, Daniel C.; Underwood, Paula; Fuller, Zachary; Moser, Matthew A.; Flegel, Ron; Gorelick, David A.; Newmeyer, Matthew N.; Concheiro, Marta; HUESTIS, MARILYN A.

    2014-01-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography–mass spectrometry (GC–MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended do...

  1. Evaluation of ephedrine, pseudoephedrine and phenylpropanolamine concentrations in human urine samples and a comparison of the specificity of DRI amphetamines and Abuscreen online (KIMS) amphetamines screening immunoassays.

    Science.gov (United States)

    Stout, Peter R; Klette, Kevin L; Horn, Carl K

    2004-01-01

    The purpose of this study was to evaluate the ability of two amphetamine class screening reagents to exclude ephedrine (EPH), pseudoephedrine (PSEPH), and phenylpropanolamine (PPA) from falsely producing positive immunoassay screening results. The study also sought to characterize the prevalence and concentration distributions of EPH, PSEPH, and PPA in samples that produced positive amphetamine screening results. Approximately 27,400 randomly collected human urine samples from Navy and Marine Corps members were simultaneously screened for amphetamines using the DRI and Abuscreen online immunoassays at a cutoff concentration of 500 ng/mL. All samples that screened positive were confirmed for amphetamine (AMP), methamphetamine (MTH), 3,4-Methylenedioxyamphetamine (MDA), 3,4-Methylenedioxymethamphetamine (MDMA), EPH, PSEPH, and PPA by gas chromatography/mass spectrometry (GC/MS). The DRI AMP immunoassay identified 1,104 presumptive amphetamine positive samples, of which only 1.99% confirmed positive for the presence of AMP, MTH, MDA, or MDMA. In contrast, the online AMP reagent identified 317 presumptive amphetamine positives with a confirmation rate for AMP, MTH, MDA, or MDMA of 7.94%. The presence of EPH, PSEPH, or PPA was confirmed in 833 of the 1,104 samples that failed to confirm positive for AMP, MTH, MDA, or MDMA; all of the 833 samples contained PSEPH. When compared to the entire screened sample set, PSEPH was present in approximately 3%, EPH in 0.9%, and PPA in 0.8% of the samples. The results indicate that cross reactivities for EPH, PSEPH, and PPA are greater than reported by the manufacturer of these reagents. The distribution of concentrations indicates that very large concentrations of EPH, PSEPH, and PPA are common.

  2. Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

    Full Text Available Abstract Background All antipsychotics work via dopamine D2 receptors (D2Rs, suggesting a critical role for D2Rs in psychosis; however, there is little evidence for a change in receptor number or pharmacological nature of D2Rs. Recent data suggest that D2Rs form dimers in-vitro and in-vivo, and we hypothesized that schizophrenia, as well as preclinical models of schizophrenia, would demonstrate altered dimerization of D2Rs, even though the overall number of D2Rs was unaltered. Methods We measured the expression of D2Rs dimers and monomers in patients with schizophrenia using Western blots, and then in striatal tissue from rats exhibiting the amphetamine-induced sensitized state (AISS. We further examined the interaction between D2Rs and the dopamine transporter (DAT by co-immunoprecipitation, and measured the expression of dopamine D2High receptors with ligand binding assays in rat striatum slices with or without acute amphetamine pre-treatment. Results We observed significantly enhanced expression of D2Rs dimers (277.7 ± 33.6% and decreased expression of D2Rs monomers in post-mortem striatal tissue of schizophrenia patients. We found that amphetamine facilitated D2Rs dimerization in both the striatum of AISS rats and in rat striatal neurons. Furthermore, amphetamine-induced D2Rs dimerization may be associated with the D2R-DAT protein-protein interaction as an interfering peptide that disrupts the D2R-DAT coupling, blocked amphetamine-induced up-regulation of D2Rs dimerization. Conclusions Given the fact that amphetamine induces psychosis and that the AISS rat is a widely accepted animal model of psychosis, our data suggest that D2R dimerization may be important in the pathophysiology of schizophrenia and may be a promising new target for novel antipsychotic drugs.

  3. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine.

    Science.gov (United States)

    Kameda, Sonia R; Fukushiro, Daniela F; Trombin, Thaís F; Procópio-Souza, Roberta; Patti, Camilla L; Hollais, André W; Calzavara, Mariana B; Abílio, Vanessa C; Ribeiro, Rosana A; Tufik, Sergio; D'Almeida, Vânia; Frussa-Filho, Roberto

    2011-04-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intraperitoneal injection of saline or amphetamine (1.0, 2.0 or 4.0 mg/kg). Seven days later, half of the mice from the saline group received a second injection of saline. The remaining animals were challenged with 2.0 mg/kg amphetamine. Following all of the injections, mice were placed in activity chambers and locomotion was quantified for 45 min. The magnitude of both the acute and sensitized locomotor stimulatory effect of amphetamine was higher in the adolescent mice. Previous experience with the test environment inhibited the acute amphetamine stimulation in both adolescent and adult mice, but facilitated the detection of elevated spontaneous locomotion in adolescent animals. These results support the notion that the adolescent period is associated with an increased risk for development of drug abuse. Additionally, they indicate a complex interaction between the environmental novelty, adolescence and amphetamine.

  4. Amphetamine administration into the ventral striatum facilitates behavioral interaction with unconditioned visual signals in rats.

    Directory of Open Access Journals (Sweden)

    Rick Shin

    Full Text Available BACKGROUND: Administration of psychomotor stimulants like amphetamine facilitates behavior in the presence of incentive distal stimuli, which have acquired the motivational properties of primary rewards through associative learning. This facilitation appears to be mediated by the mesolimbic dopamine system, which may also be involved in facilitating behavior in the presence of distal stimuli that have not been previously paired with primary rewards. However, it is unclear whether psychomotor stimulants facilitate behavioral interaction with unconditioned distal stimuli. PRINCIPAL FINDINGS: We found that noncontingent administration of amphetamine into subregions of the rat ventral striatum, particularly in the vicinity of the medial olfactory tubercle, facilitates lever pressing followed by visual signals that had not been paired with primary rewards. Noncontingent administration of amphetamine failed to facilitate lever pressing when it was followed by either tones or delayed presentation or absence of visual signals, suggesting that visual signals are key for enhanced behavioral interaction. Systemic administration of amphetamine markedly increased locomotor activity, but did not necessarily increase lever pressing rewarded by visual signals, suggesting that lever pressing is not a byproduct of heightened locomotor activity. Lever pressing facilitated by amphetamine was reduced by co-administration of the dopamine receptor antagonists SCH 23390 (D1 selective or sulpiride (D2 selective. CONCLUSIONS: Our results suggest that amphetamine administration into the ventral striatum, particularly in the vicinity of the medial olfactory tubercle, activates dopaminergic mechanisms that strongly enhance behavioral interaction with unconditioned visual stimuli.

  5. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Hafizi, Hamid [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Najafi Chermahini, Alireza, E-mail: anajafi@cc.iut.ac.ir [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Mohammadnezhad, Gholamhossein [Department of Chemistry, Isfahan University of Technology, Isfahan 84156-83111 (Iran, Islamic Republic of); Teimouri, Abbas [Chemistry Department, Payame Noor University (PNU), Tehran 19395-4697 (Iran, Islamic Republic of)

    2015-02-28

    Graphical abstract: - Highlights: • Interaction energy between several armchair CNTs and amphetamine is investigated. • The adsorption of amphetamine molecule is observed to be exothermic and physical in nature. • HOMO–LUMO for pure CNTs, amphetamine and their corresponded complexes are studied. • Density of states (DOS) near the Fermi level is calculated and presented. - Abstract: The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of −1.13 to −1.88 and −1.27 to −2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule.

  6. Comparison of the sensitivity and specificity of six immunoassays for the detection of amphetamines in urine.

    Science.gov (United States)

    Verstraete, Alain G; Heyden, Fien V

    2005-01-01

    We analyzed 225 urine samples with FPIA (Abbott Amphetamine/Methamphetamine II on ADx and AxSYM), EMIT (Emit II Plus Monoclonal Amphetamine/Metamphetamine assay and EMIT II Plus Amphetamines assay, EMIT N), and KIMS (standard protocol and MDMA protocol, KIMS and KIMS X, respectively) immunoassays and compared their sensitivity and specificity. All assays were calibrated and used semi-quantitatively. All samples that screened positive by any amphetamine screening method and 15% of the negative samples were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS-MS). A sample was considered positive for amphetamines if amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedio-xyethylamphetamine, or methylenedioxyamphetamine was present at 250 ng/mL. Ninety (40%) of the samples were positive by LC-MS-MS. The areas under the receiver operating characteristic curve varied between 0.972 (KIMS X) and 1.000 (ADx). The optimal cut-off concentrations varied between 271 ng/mL (EMIT N) and 723 ng/mL (AxSYM). The sensitivity was 100% for ADx and between 93 and 95% for the other assays. The specificity varied between 88% (KIMS) and 100% (EMIT N). Use of a 500 ng/mL screening cut-off would have resulted in identical or very similar results for ADx and KIMS X and large increases in the false positives for AxSYM and EMIT and the false negatives for EMIT N and KIMS.

  7. Food consumption and weight gain after cessation of chronic amphetamine administration.

    Science.gov (United States)

    Orsini, Caitlin A; Ginton, Guy; Shimp, Kristy G; Avena, Nicole M; Gold, Mark S; Setlow, Barry

    2014-07-01

    Cessation of drug use often coincides with increased food consumption and weight gain in recovering addicts. However, it is not known whether this phenomenon (particularly the weight gain) is uniquely human, or whether it represents a consequence of drug cessation common across species. To address this issue, rats (n = 10/group) were given systemic injections of D-amphetamine (3 mg/kg) or an equal volume of saline vehicle for 9 consecutive days. Beginning 2 days after the final injection, rats were given free access to a highly palatable food mixture (consisting of sugar and butter) along with their standard chow diet, and food consumption and body weight were measured every 48 h for 30 days. Consistent with clinical observations, amphetamine-treated rats showed a greater increase in body weight over the course of the 30 days relative to vehicle-treated rats. Surprisingly, there was no difference in highly palatable food consumption between amphetamine- and vehicle-treated groups, but the amphetamine-treated group consumed significantly more standard chow than the control group. The finding that a history of chronic amphetamine exposure increases food consumption is consistent with previous work in humans showing that withdrawal from drugs of abuse is associated with overeating and weight gain. The current findings may reflect amphetamine-induced sensitization of mechanisms involved in reward motivation, suggesting that weight gain following drug cessation in humans could be due to similar mechanisms.

  8. Amphetamine affects the behavioral outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Prasad, R M; Dose, J M; Dhillon, H S; Carbary, T; Kraemer, P J

    1995-01-01

    This study examined the effects of (D)-amphetamine, methoxamine (an al-adrenergic receptor agonist), and prazosin (an al-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid percussion brain injury. Rats trained to perform a beam walking task were subjected to brain injury of moderate severity (2.1-2.2 atm). At 10 min after injury, rats were treated with amphetamine, methoxamine or prazosin at two different dose levels. Amphetamine-treated animals displayed significantly lower impairment in beam walking ability from days 1 to 5 after brain injury. Neither methoxamine nor prazosin significantly affected the impairment in beam walking ability from day 1 to day 7 after injury. However, prazosin treatment at both dose levels increased the post-injury mortality and the incidences of failure to recovery from hemiplegia. Amphetamine-treatment at 4 mg/kg, but not at 2 mg/kg, improved the spatial learning abilities of the injured animals. Neither methoxamine nor prazosin affected the spatial learning abilities. These results indicate that amphetamine facilitated beam walking recovery and improved cognitive function after concussive fluid percussion injury. Although the methoxamine experiments suggest that the norepinephrine-α1-adrenergic receptor system may not be involved in the pathophysiology of fluid percussion brain injury, our results with amphetamine (beneficial effects) and prazosin (deleterious effects) and the results observed in other models of brain injury point out that further investigations are necessary to understand the role of a1-adrenergic receptors in brain injury.

  9. The ugly side of amphetamines: short- and long-term toxicity of 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), methamphetamine and D-amphetamine.

    Science.gov (United States)

    Steinkellner, Thomas; Freissmuth, Michael; Sitte, Harald H; Montgomery, Therese

    2011-01-01

    Amphetamine ('Speed'), methamphetamine ('Ice') and its congener 3,4-methylenedioxymethamphetamine (MDMA; 'Ecstasy') are illicit drugs abused worldwide for their euphoric and stimulant effects. Despite compelling evidence for chronic MDMA neurotoxicity in animal models, the physiological consequences of such toxicity in humans remain unclear. In addition, distinct differences in the metabolism and pharmacokinetics of MDMA between species and different strains of animals prevent the rationalisation of realistic human dose paradigms in animal studies. Here, we attempt to review amphetamine toxicity and in particular MDMA toxicity in the pathogenesis of exemplary human pathologies, independently of confounding environmental factors such as poly-drug use and drug purity.

  10. Amphetamine and methamphetamine induced psychosis: toxicological findings, comparison with acute symptoms of schizophrenia and transition of diagnoses. A clinical investigation

    OpenAIRE

    Medhus, Sigrid

    2014-01-01

    Background: There is a long-standing debate about the relationship between amphetamines and psychoses. While some have found psychoses induced by amphetamines to be indistinguishable from schizophrenia, others have found that psychoses induced by amphetamines, in contrast to schizophrenia, were characterized by visual hallucinations and lack of thought disorder. It has also been discusses whether there really are sharp boundaries between the two diagnoses, and whether there is a transition be...

  11. Effects of amphetamine on pro-social ultrasonic communication in juvenile rats: Implications for mania models.

    Science.gov (United States)

    Engelhardt, K-Alexander; Fuchs, Eberhard; Schwarting, Rainer K W; Wöhr, Markus

    2017-03-01

    Communication is the act of information transfer between sender and receiver. In rats, vocal communication can be studied through ultrasonic vocalizations (USV). 50-kHz USV occur in appetitive situations, most notably juvenile play, likely expressing the sender׳s positive affective state. Such appetitive 50-kHz USV serve important pro-social communicative functions and elicit social exploratory and approach behavior in the receiver. Emission of 50-kHz USV can be induced pharmacologically by the administration of psychostimulant drugs, such as amphetamine. However, it is unknown whether amphetamine affects the pro-social communicative function of 50-kHz USV in the receiver. We therefore assessed dose-response effects of amphetamine (0.0mg/kg, 0.5mg/kg, 1.0mg/kg, 2.5mg/kg, 5.0mg/kg) on pro-social ultrasonic communication on both, sender and receiver, in juvenile rats. We found an inverted U-shaped effect of amphetamine on 50-kHz USV emission, with 50-kHz USV levels being strongly enhanced by moderate doses, yet less prominent effects were seen following the highest dose. Likewise, amphetamine exerted inverted U-shaped effects on social exploratory and approach behavior induced by playback of appetitive 50-kHz USV. Social approach was enhanced by moderate amphetamine doses, but completely abolished following the highest dose. Amphetamine further dose-dependently promoted the emission of 50-kHz USV following playback of appetitive 50-kHz USV, indicating more vigorous attempts to establish social proximity. Our results support an important role of dopamine in closing a perception-and-action-loop through linking mechanisms relevant for detection and production of social vocalizations. Moreover, our approach possibly provides a new means to study mania-like aberrant social interaction and communication in animal models for bipolar disorder.

  12. Response of CEDIA amphetamines assay after a single dose of bitter orange.

    Science.gov (United States)

    Nguyen, DiemThuy T; Bui, Linda T; Ambrose, Peter J

    2006-04-01

    Bitter orange has recently been substituted as an ingredient in many "ephedra-free" dietary supplements used for weight loss. The primary active ingredient in bitter orange is synephrine. Previous reports have documented false-positive results from ephedrine with urine amphetamine assays. Because of the similarity in chemical structure of ephedrine and synephrine, it is hypothesized that ingestion of a bitter orange supplement may have the potential to cause false-positive results with urine amphetamine assays. The purpose of this study was to determine the response of the CEDIA Amphetamines Assay after ingestion of bitter orange. Six healthy adult male volunteers were administered a single oral dose of Nature's Way Bitter Orange, a 900-mg dietary supplement extract standardized to 6% synephrine. Urine specimens were collected at baseline and 3 and 6 hours post-administration. Additional urine specimens were collected from 1 subject at 9, 12, and 15 hours after administration. All specimens were analyzed by the CEDIA Amphetamines Assay. Urine specific gravity and pH also were measured. All urine specimens demonstrated a negative response to the CEDIA Amphetamines Assay. Urine specific gravity ranged from 1.007 to 1.028, and pH ranged from 5.0 to 7.0; thus, reducing the possibility that the negative results were caused by diluted specimens or reduced excretion of synephrine into alkaline urine. This information will be of value when health care providers or those who interpret drug screens are asked to provide consultation regarding the interference of bitter orange supplements with the CEDIA Amphetamines Assay. A single-dose of Nature's Way Bitter Orange was not found to cause a false-positive response to the CEDIA Amphetamines Assay in 6 healthy adult male volunteers.

  13. The N terminus of monoamine transporters is a lever required for the action of amphetamines.

    Science.gov (United States)

    Sucic, Sonja; Dallinger, Stefan; Zdrazil, Barbara; Weissensteiner, René; Jørgensen, Trine N; Holy, Marion; Kudlacek, Oliver; Seidel, Stefan; Cha, Joo Hwan; Gether, Ulrik; Newman, Amy H; Ecker, Gerhard F; Freissmuth, Michael; Sitte, Harald H

    2010-04-02

    The serotonin transporter (SERT) terminates neurotransmission by removing serotonin from the synaptic cleft. In addition, it is the site of action of antidepressants (which block the transporter) and of amphetamines (which induce substrate efflux). We explored the functional importance of the N terminus in mediating the action of amphetamines by focusing initially on the highly conserved threonine residue at position 81, a candidate site for phosphorylation by protein kinase C. Molecular dynamics simulations of the wild type SERT, compared with its mutations SERT(T81A) and SERT(T81D), suggested structural changes in the inner vestibule indicative of an opening of the inner vestibule. Predictions from this model (e.g. the preferential accumulation of SERT(T81A) in the inward conformation, its reduced turnover number, and a larger distance between its N and C termini) were verified. Most importantly, SERT(T81A) (and the homologous mutations in noradrenaline and dopamine) failed to support amphetamine-induced efflux, and this was not remedied by aspartate at this position. Amphetamine-induced currents through SERT(T81A) were comparable with those through the wild type transporter. Both abundant Na(+) entry and accumulation of SERT(T81A) in the inward facing conformation ought to favor amphetamine-induced efflux. Thus, we surmised that the N terminus must play a direct role in driving the transporter into a state that supports amphetamine-induced efflux. This hypothesis was verified by truncating the first 64 amino acids and by tethering the N terminus to an additional transmembrane helix. Either modification abolished amphetamine-induced efflux. We therefore conclude that the N terminus of monoamine transporters acts as a lever that sustains reverse transport.

  14. Development and evaluation of an improved method for screening of amphetamines.

    Science.gov (United States)

    Shindelman, J; Mahal, J; Hemphill, G; Pizzo, P; Coty, W A

    1999-10-01

    We developed a homogeneous immunoassay method to eliminate false-positive amphetamine results caused by cross-reactive substances, including over-the-counter allergy and cold medications. This method uses a neutralizing antibody that binds to amphetamines but does not bind to the labeled amphetamine conjugate used in the assay. The amount of neutralizing antibody is sufficient to reduce the assay signal resulting from authentic amphetamine and methamphetamine, but not the signal resulting from cross-reactants. This concept was implemented using the CEDIA DAU Amphetamines assay on Hitachi 747 and 717 clinical chemistry analyzers. Urine samples were tested using the standard, unmodified reagents in one channel and reagents containing the neutralizing antibody in a second channel. The difference in rate between the two tests was calculated by the analyzer; true-positive samples showed a significantly greater decrease in assay signal in response to neutralizing antibody as compared with false-positive samples. The neutralization method was evaluated in two studies using 448 samples that tested positive in the initial CEDIA DAU Amphetamines screening test. The samples were separated into categories of 154 true-positive samples and 294 false-positive samples based upon a secondary screen with the Abbott FPIA Amphetamines assay followed by gas chromatography-mass spectrometry (GC-MS) testing using the HHS (SAMHSA) cutoff criteria. The CEDIA neutralization test successfully identified all 154 of the GC-MS confirmed positive samples. The test successfully identified as false positive 251 out of the 294 (85.4%) samples that failed to confirm by GC-MS.

  15. Frequency of false positive amphetamine screens due to bupropion using the Syva EMIT II immunoassay.

    Science.gov (United States)

    Casey, Erica R; Scott, Mitchell G; Tang, Schirin; Mullins, Michael E

    2011-06-01

    Bupropion is a commonly prescribed, monocyclic antidepressant often used as an aid for smoking cessation. Several case reports have described false positive amphetamine urine drug screens (UDS) associated with bupropion. We sought to determine whether false positive amphetamine UDS due to the use of bupropion would be a frequent occurrence. We conducted an IRB-approved, retrospective chart review of all emergency department patients who underwent UDS between 1 January 2006 and 31 July 2007. All urine samples were screened using Syva EMIT II Plus immunoassay reagents. All positive screens underwent confirmation by gas chromatography (GC). We reviewed the records of patients with positive amphetamine UDS. We documented prescription use of bupropion, other antidepressants, stimulants, antipsychotics, and anti-hypertensives. We recorded evidence of polysubstance abuse (PSA) as patients who had had a documented diagnosis or laboratory evidence of abuse of at least two substances (drugs or ethanol). Of 10,011 urine drug screens, 362 (3.6%) were positive for amphetamine. GC confirmed amphetamines in 234 (65%), but failed to confirm in 128 (35%). Among the 234 confirmed, records reflected use of bupropion in three (1.3%), other antidepressants in 38 (16%), antipsychotics in 17 (8%), and amphetamine in 50 (21%). Records indicated evidence of PSA in 55 (24%). Among the 128 which failed to confirm, records reflected prescription use of bupropion in 53 (41%). None whose drug screen failed to confirm had evidence of PSA. Therapeutic use of bupropion appears to be the most frequent cause of false positive urine drug screens for amphetamines in our population.

  16. Does COMT genotype influence the effects of d-amphetamine on executive functioning?

    Science.gov (United States)

    Wardle, M C; Hart, A B; Palmer, A A; de Wit, H

    2013-02-01

    In a widely cited study, Mattay et al. reported that amphetamine (0.25 mg/kg oral, or 17 mg for a 68 kg individual) impaired behavioral and brain indices of executive functioning, measured using the Wisconsin Card Sorting Task (WCST) and N-Back working memory task, in 6 individuals homozygous for the met allele of the val158met polymorphism in the catechol-O-methyltransferase (COMT) gene, whereas it improved executive functioning in 10 individuals homozygous for the more active val allele. We attempted to replicate their behavioral findings in a larger sample, using similar executive functioning tasks and a broader range of amphetamine doses. Over four sessions, n = 200 healthy normal adults received oral placebo, d-amphetamine 5, 10, and 20 mg (average of 0.07, 0.15 and 0.29 mg/kg), under counterbalanced double-blind conditions and completed WCST and N-back tests of executive functioning. Amphetamine had typical effects on blood pressure and processing speed but did not affect executive functioning. COMT genotype (val158met) was not related to executive functioning under placebo or amphetamine conditions, even when we compared only the homozygous val/val and met/met genotypes at the highest dose of amphetamine (20 mg). Thus, we were not able to replicate the behavioral interaction between COMT and amphetamine seen in Mattay et al. We discuss possible differences between the studies and the implications of our findings for the use of COMT genotyping to predict clinical responses to dopaminergic drugs, and the use of intermediate phenotypes in genetic research.

  17. Differential effects of endomorphin-1 and -2 on amphetamine sensitization: neurochemical and behavioral aspects.

    Science.gov (United States)

    Chen, J C; Liang, K W; Huang, E Y

    2001-03-01

    Mu-opioid receptors are known to modulate mesolimbic dopaminergic activity in the ventral tegmental area via disinhibition of GABA-containing neurons. Recently, two novel tetrapeptides, endomorphin-1 and endomorphin-2, were identified in the mammalian brain and reported to have high binding affinities toward mu-opioid receptors. To determine if endomorphins would modulate the development of amphetamine sensitization, we administered endomorphins locally into the rat brain followed by behavioral and neurochemical examinations. The results indicate that rats pretreated with endomorphin-1 or -2 (5 microg per side for 7 days) in the ventral tegmental area developed locomotor sensitization to the challenge injection of amphetamine (1 mg/kg). On the other hand, when endomorphins were given in the lateral ventricle (20 microg for 5 days) of amphetamine-sensitized rats (5 mg/kg x 14 days) during the withdrawal period (w5-w9), neither peptide had a modulatory effect on locomotor sensitization. Biochemical analyses revealed that treatment with endomorphins in the ventral tegmental area significantly increased the levels of glutamate in the medial prefrontal cortex and ventral and dorsal striatum to levels comparable to those observed in the amphetamine-sensitized rats. In the same animals, endomorphins also caused decreases in the levels of serotonin and its metabolite, 5-hydroxyindoleacetic acid, in the medial prefrontal cortex. Interestingly, although there was no behavioral significance, endomorphin-1 treatment in the lateral ventricle of control and amphetamine-sensitized rats during withdrawal resulted in decreases of GABA, aspartate, dopamine, and its metabolite 3,4-dihydroxyphenylacetic acid in the ventral striatum. We conclude that endomorphins, by stimulating the mu-opioid receptors in the ventral tegmental area, could sensitize the behavioral response to amphetamine. The results also demonstrate that there are differential responses between endomorphin-1 and -2 on

  18. Determination of enantiomeric amphetamines as metabolites of illicit amphetamines and selegiline in urine by capillary electrophoresis using modified beta-cyclodextrin.

    Science.gov (United States)

    Heo, Y J; Whang, Y S; In, M K; Lee, K J

    2000-05-12

    The determination of enantiomeric amphetamine and methamphetamine in urine samples is important in order to distinguish use of the prescription drug selegiline (metabolized to R(-)-A and R(-)-MA) from the illicit use of S(+)-A and S(+)-MA. For the analysis of enantiomeric amphetamine (A) and methamphetamine (MA) in biological samples, the optimization of analytical condition was performed by capillary electrophoresis using chiral selectors including beta-cyclodextrin, carboxymethyl-beta-cyclodextrin and 2-hydroxypropyl-beta-cyclodextrin. We have examined the factors to obtain the best chiral resolutions, separation efficiency and sensitivity, and wide concentration linearity. Optimum resolutions were achieved using 100 mM phosphate buffer, pH 2.5, containing 10 mM of carboxymethyl-beta-cyclodextrin. This method was applied for the quantitative determination of enantiomeric amphetamine and methamphetamine in urine samples obtained from patients taking illicit amphetamines or from rats and patients taking selegiline. Acceptable quantitative results in terms of resolution, precision, sensitivity and linearity were obtained from the real urine samples containing wide-ranging concentrations of A and MA by using two concentrations of internal standards, alpha(+)- (1 microg/ml) and beta-phenylethylamine (50 microg/ml).

  19. Amphetamines promote mitochondrial dysfunction and DNA damage in pulmonary hypertension

    Science.gov (United States)

    Chen, Pin-I; Cao, Aiqin; Miyagawa, Kazuya; Tojais, Nancy F.; Hennigs, Jan K.; Li, Caiyun G.; Sweeney, Nathaly M.; Inglis, Audrey S.; Wang, Lingli; Li, Dan; Ye, Matthew; Feldman, Brian J.

    2017-01-01

    Amphetamine (AMPH) or methamphetamine (METH) abuse can cause oxidative damage and is a risk factor for diseases including pulmonary arterial hypertension (PAH). Pulmonary artery endothelial cells (PAECs) from AMPH-associated-PAH patients show DNA damage as judged by γH2AX foci and DNA comet tails. We therefore hypothesized that AMPH induces DNA damage and vascular pathology by interfering with normal adaptation to an environmental perturbation causing oxidative stress. Consistent with this, we found that AMPH alone does not cause DNA damage in normoxic PAECs, but greatly amplifies DNA damage in hypoxic PAECs. The mechanism involves AMPH activation of protein phosphatase 2A, which potentiates inhibition of Akt. This increases sirtuin 1, causing deacetylation and degradation of HIF1α, thereby impairing its transcriptional activity, resulting in a reduction in pyruvate dehydrogenase kinase 1 and impaired cytochrome c oxidase 4 isoform switch. Mitochondrial oxidative phosphorylation is inappropriately enhanced and, as a result of impaired electron transport and mitochondrial ROS increase, caspase-3 is activated and DNA damage is induced. In mice given binge doses of METH followed by hypoxia, HIF1α is suppressed and pulmonary artery DNA damage foci are associated with worse pulmonary vascular remodeling. Thus, chronic AMPH/METH can induce DNA damage associated with vascular disease by subverting the adaptive responses to oxidative stress. PMID:28138562

  20. The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

    Science.gov (United States)

    Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

    2017-03-15

    Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence.

  1. Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine-induced behaviours.

    Science.gov (United States)

    Ripley, Tamzin L; Dunworth, Sarah J; Stephens, David N

    2002-09-01

    It has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330-1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94-98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine-induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467-475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid-diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25-1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a

  2. Determination of ketamine and amphetamines in hair by LC/MS/MS.

    Science.gov (United States)

    Tabernero, María Jesús; Felli, Maria Linda; Bermejo, Ana María; Chiarotti, Marcello

    2009-12-01

    A liquid chromatography-tandem mass spectrometry method was developed for the determination of ketamine (with its metabolite norketamine) and some amphetamines (amphetamine, methamphetamine, methylenedioxyamphetamine, and 3,4-methylenedioxymethamphetamine). This method was developed to determine these compounds in hair and is able to simultaneously quantify all of them in human hair. Hair samples (20 mg) were washed and pulverized, and an extraction with formic acid (0.01%) and ultrasonication for 4 h was used. Deuterated analogs of the analytes were used as internal standards for quantification. Linearity from 0.5 to 25 ng/mg was obtained for both ketamine (and norketamine) and amphetamines with correlation coefficients exceeding 0.99. The limit of detection and the limit of quantification obtained were 0.1 and 0.5 ng/mg, respectively, for ketamine and amphetamines. A total of 25 hair samples from known drug abusers (relating to designer drug consumption or consumption of amphetamines) were examined by this validated method. The results show that the proposed method is suitable for testing these drugs in a single sample of hair. In addition, it is simpler and faster than analysis by conventional methods such as gas chromatography-mass spectrometry, which usually require a more laborious extraction procedure and, in most of cases, an additional derivatization process.

  3. A rapid method for the extraction, enantiomeric separation and quantification of amphetamines in hair.

    Science.gov (United States)

    Strano-Rossi, Sabina; Botrè, Francesco; Bermejo, Ana Maria; Tabernero, Maria Jesús

    2009-12-15

    This paper presents a rapid and sensitive method for the determination and chiral separation of amphetamines and related designer drugs in hair samples. The substances are extracted from hair matrix by a 30 min treatment with a saturated carbonate buffer at pH 10 under ultrasonication. A commercial chiral derivatizing agent, trifluoroacetyl-prolyl chloride, is then added to the solution that is directly extracted with hexane and subsequently analyzed by GC/MS in SIM mode. R and S isomers of amphetamine, methamphetamine, MDA, MDMA and MDEA can be separated and detected with a limit of detection of 0.1 ng/mg for amphetamine, methamphetamine and MDA, and of 0.2 ng/mg for MDMA and MDEA. The method was then applied to 12 samples from suspected amphetamines abusers, showing the presence of both isomers of amphetamine and MDMA in one sample (27 and 1.5 ng/mg, respectively) and of MDMA in further eight samples, in concentrations ranging from traces to 2.7 ng/mg. No differences were observed in the disposition of different isomers in hair.

  4. The risky cocktail: what combination effects can we expect between ecstasy and other amphetamines?

    Science.gov (United States)

    Dias da Silva, Diana; Carmo, Helena; Silva, Elisabete

    2013-01-01

    The recreational and illicit use of amphetaminic designer compounds, specially 3,4-methylenedioxymethamphetamine (MDMA; Ecstasy), is of concern worldwide. Such psychostimulating drugs are frequently present as complex mixtures in 'rave' pills, making concomitant polysubstance use a common trend. However, the understanding of possible combination effects with these substances is still scarce. The present study was aimed at predicting the cytotoxic effects of mixtures of four amphetaminic derivatives: MDMA, methamphetamine, 4-methylthioamphetamine and d-amphetamine in a human hepatoma cell line. Concentration-response curves for all single-mixture components were recorded by the MTT assay. Data obtained for individual agents were then used to compute the additivity expectations for mixtures of definite composition, using the pharmacological models of concentration addition (CA) and independent action. By comparing the predicted calculations with the experimentally observed effects, we concluded that CA accurately predicts the combination of amphetamines, which act together to generate additive effects over a large range of concentrations. Notably, we observed substantial mixture effects even when each drug was present at low concentrations, which individually produced unnoticeable effects. Nonetheless, for all tested mixtures, a small deviation from additivity was observed towards higher concentrations, particularly at high effect levels. A possible metabolic interaction, which could explain such deviation, was investigated, and it was observed that at higher mixture concentrations increased MDMA metabolism could be contributing to divergences from additivity. In conclusion, the present work clearly demonstrates that potentially harmful interactions among amphetaminic drugs are expected when these drugs are taken concomitantly.

  5. Frontline immunochromatographic device for on-site urine testing of amphetamines: laboratory validation using authentic specimens.

    Science.gov (United States)

    Beck, O; Kraft, M; Moeller, M R; Smith, B L; Schneider, S; Wennig, R

    2000-03-01

    We evaluated a new test device for amphetamines and methamphetamines (Frontline, cut-off limit 300 ng/mL) using authentic clinical and forensic specimens. The device is based on immunochromatography and is dipped into urine and read visually by comparison with a colour scale after a few minutes. A total of 658 specimens were tested by comparing results of the screening procedure with established immunoassays. Discordant results were further investigated by gas chromatography mass spectrometry or gas chromatography (with flame ionization detector). The Frontline device had a sensitivity of 93% and a specificity of 98%. When specimens were classified by urine amphetamine concentration, close agreement was obtained at concentrations below 150 ng/mL and above 1000 ng/mL. A small number of specimens with amphetamine concentrations between 300 and 1000 ng/mL tested negative in the Frontline test. This finding could to some extent be explained by the enantioselectivity of the antibodies in the Frontline test to d-amphetamine. We conclude that the performance of the Frontline test device for amphetamines is adequate for presumptive clinical and forensic screening.

  6. Determination of amphetamines in human urine by headspace solid-phase microextraction and gas chromatography.

    Science.gov (United States)

    Raikos, Nikolaos; Christopoulou, Klio; Theodoridis, Georgios; Tsoukali, Heleni; Psaroulis, Dimitrios

    2003-06-05

    Solid-phase microextraction (SPME) is under investigation for its usefulness in the determination of a widening variety of volatile and semivolatile analytes in biological fluids and materials. Semivolatiles are increasingly under study as analytical targets, and difficulties with small partition coefficients and long equilibration times have been identified. Amphetamines were selected as semivolatiles exhibiting these limitations and methods to optimize their determination were investigated. A 100- micro m polydimethylsiloxane (PDMS)-coated SPME fiber was used for the extraction of the amphetamines from human urine. Amphetamine determination was made using gas chromatography (GC) with flame-ionization detection (FID). Temperature, time and salt saturation were optimized to obtain consistent extraction. A simple procedure for the analysis of amphetamine (AMP) and methamphetamine (MA) in urine was developed and another for 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methamphetamine (MDMA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) using headspace solid-phase microextraction (HS-SPME) and GC-FID. Higher recoveries were obtained for amphetamine (19.5-47%) and methamphetamine (20-38.1%) than MDA (5.1-6.6%), MDMA (7-9.6%) and MDEA (5.4-9.6%).

  7. Reinforcer magnitude affects delay discounting and influences effects of d-amphetamine in rats.

    Science.gov (United States)

    Krebs, Christopher A; Reilly, William J; Anderson, Karen G

    2016-09-01

    Impulsive choice in humans can be altered by changing reinforcer magnitude; however, this effect has not been found in rats. Current levels of impulsive choice can also influence effects of d-amphetamine. This study used a within-subject assessment to determine if impulsive choice is sensitive to changes in reinforcer magnitude, and whether effects of d-amphetamine are related to current levels of impulsive choice. A discounting procedure in which choice was for a smaller reinforcer available immediately or a larger reinforcer available after a delay that increased within session was used. Reinforcer magnitude was manipulated between conditions and impulsive choice was quantified using area under the curve (AUC). In the Smaller-Magnitude (SM) Condition, choice was between one food pellet and three food pellets. In the Larger-Magnitude (LM) Condition, choice was between two food pellets and six food pellets. Impulsive choice was greater in the SM Condition compared to the LM Condition. Further, effects of d-amphetamine (0.1-1.8mg/kg) were related to differences in impulsive choice. d-Amphetamine increased impulsive choice in the LM Condition, but had no effect on impulsive choice in the SM Condition. Overall, these results show that impulsive choice in rats is sensitive to changes in reinforcer magnitude, and that effects of d-amphetamine are influenced by current levels of impulsive choice.

  8. delta(13)C and delta(2)H isotope ratios in amphetamine synthesized from benzaldehyde and nitroethane.

    Science.gov (United States)

    Collins, Michael; Salouros, Helen; Cawley, Adam T; Robertson, James; Heagney, Aaron C; Arenas-Queralt, Andrea

    2010-06-15

    Previous work in these laboratories and by Butzenlechner et al. and Culp et al. has demonstrated that the delta(2)H isotope value of industrial benzaldehyde produced by the catalytic oxidation of toluene is profoundly positive, usually in the range +300 per thousand to +500 per thousand. Synthetic routes leading to amphetamine, methylamphetamine or their precursors and commencing with such benzaldehyde may be expected to exhibit unusually positive delta(2)H values. Results are presented for delta(13)C and delta(2)H isotope values of 1-phenyl-2-nitropropene synthesized from an industrial source of benzaldehyde, having a positive delta(2)H isotope value, by a Knoevenagel condensation with nitroethane. Results are also presented for delta(13)C and delta(2)H isotope values for amphetamine prepared from the resulting 1-phenyl-2-nitropropene. The values obtained were compared with delta(13)C and delta(2)H isotope values obtained for an amphetamine sample prepared using a synthetic route that did not involve benzaldehyde. Finally, results are presented for samples of benzaldehyde, 1-phenyl-2-nitropropene and amphetamine that had been seized at a clandestine amphetamine laboratory.

  9. Determination of Amphetamine, Amfepramone and Fenproporex in Urine Samples by HPLC-DAD: Application to a Population of Brazilian Truck Drivers

    OpenAIRE

    Takitane,Juliana; Almeida, Rafael M.; Tiago F. de Oliveira; Prado,Natanael V.; Muñoz,Daniel R.; Leyton,Vilma; Yonamine, Mauricio

    2016-01-01

    Commercially available immunoassay tests are designed to detect the presence of amphetamine/methamphetamine or methylenodioxyamphetamines. However, it is known that Brazilian truck drivers also report the use of other illicit amphetamines, such as amfepramone and fenproporex. Thus, a method was developed and validated in order to quantify amphetamine-type stimulants (amphetamine, fenproporex and amfepramone) in urine by high performance liquid chromatography with diode array detection (HPLC-D...

  10. Effects of amphetamine on dopamine release in the rat nucleus accumbens shell region depend on cannabinoid CB1 receptor activation

    NARCIS (Netherlands)

    Kleijn, J.; Wiskerke, J.; Cremers, T. I. F. H.; Schoffelmeer, A. N. M.; Westerink, B. H. C.; Pattij, T.

    2012-01-01

    The psychostimulant drug amphetamine is often prescribed to treat Attention-Deficit/Hyperactivity Disorder. The behavioral effects of the psychostimulant drug amphetamine depend on its ability to increase monoamine neurotransmission in brain regions such as the nucleus accumbens (NAC) and medial pre

  11. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Brandt-Christensen, Anne Mette; Andersen, M B; Fink-Jensen, A

    2006-01-01

    inhibit (-)-apomorphine-induced behaviours in non-human primates at doses that do not cause EPS. When (-)-OSU6162 was tested against d-amphetamine-induced behaviours a separation between dose levels that inhibit d-amphetamine effects and cause EPS was not observed. The data further substantiate a role...... for low affinity DA D2 antagonists in the pharmacological treatment of psychosis....

  12. [Death after the intake of amphetamine/ecstasy: two case reports].

    Science.gov (United States)

    Wöllner, Kirsten; Stockhausen, Sarah; Mußhoff, Frank; Madea, Burkhard

    2015-01-01

    Synthetic amphetamines such as 3,4-methylenedioxy-N-methylamphetamine (MDMA, Ecstasy) have become recreational drugs in German discotheques because of their euphoric and mood-brightening effects. However, their consumption involves considerable risks, which may even be lethal under certain circumstances. A 19-year-old man was taken to a university hospital for suspected intoxication with a narcotic drug, where he died the next day. As cause of death "fulminant liver failure" was diagnosed. In blood from the femoral vein, MDMA was found in a concentration of 4.27 mg/l. Histological examination showed acute necrosis of the liver and parenchymatous bleeding. The second case is that of a 39-year-old man who collapsed at his workplace and died in hospital shortly afterwards. In his rucksack, a small bag with 1.6 g of amphetamine was found. Analysis of blood from the femoral vein showed an amphetamine concentration of 1.08 mg/l.

  13. Effects of d-Amphetamine and Haloperidol on Modulation of the Human Acoustic Startle Response

    Directory of Open Access Journals (Sweden)

    Hossein Kaviani

    2006-04-01

    Full Text Available "nObjective:This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. "n "n Method:Sixty participants, in two groups (one receiving haloperidol and the other receiving amphetamine were tested using electromyography (EMG to measure eye-blink muscle (orbicular oculi while different emotions were induced by six 2-minute film clips. Results:An affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. Conclusion: The methodological and theoretical aspects of the study and findings will be discussed.

  14. Choosing between GC FTIR and GC MS spectra for an efficient intelligent identification of illicit amphetamines

    Science.gov (United States)

    Gosav, S.; Dinica, R.; Praisler, M.

    2008-09-01

    In this paper we are presenting a comparative analysis between several expert systems built for the identification of illicit amphetamines based on their GC-FTIR and GC-MS spectra. The systems were built using Artificial Neural Networks (ANNs), and are dedicated to the recognition of amphetamines. Structure-activity relationships are incorporated into the knowledge base, allowing the systems to identify the amphetamines according to their toxicological activity (stimulant or hallucinogenic). The results show that GC-FTIR data are much more relevant for the efficiency of the expert systems, probably due to the fact that these spectra constitute a "fingerprint" of the molecular structures. We are also presenting a spectroscopic analysis in order to evaluate the relevance of each type of input variable (absorption and abundance) on which the recognition of an unknown sample is based.

  15. Application of solid-phase microextraction combined with derivatization to the enantiomeric determination of amphetamines.

    Science.gov (United States)

    Cháfer-Pericás, C; Campíns-Falcó, P; Herráez-Hernández, R

    2006-03-18

    The utility of combining chiral derivatization and solid-phase microextraction (SPME) for the enantiomeric analysis of primary amphetamines by liquid chromatography has been investigated. Different derivatization/extraction strategies have been evaluated and compared using the chiral reagent o-phthaldialdehyde (OPA)-N-acetyl-l-cysteine (NAC) and fibres with a Carbowax-templated resin coating. Amphetamine, norephedrine and 3,4-methylenedioxyamphetamine (MDA) were used as model compounds. On the basis of the results obtained, a new method is presented based on the derivatization of the analytes in solution followed by SPME of the OPA-NAC derivatives formed. The proposed conditions have been applied to determine the compounds of interest at low ppm levels (urine samples. Data on the linearity, reproducibility, sensitivity and selectivity are given. The utility of the described procedure for the quantification of amphetamine, norephedrine and MDA enantiomers in different kind of samples is also discussed.

  16. Prohibition or coffee shops: regulation of amphetamine and methylphenidate for enhancement use by healthy adults.

    Science.gov (United States)

    Dubljević, Veljko

    2013-01-01

    This article analyzes appropriate public policies for enhancement use of two most important stimulant drugs: Ritalin (methylphenidate) and Adderall (mixed amphetamine salts). The author argues that appropriate regulation of cognition enhancement drugs cannot be a result of a general discussion on cognitive enhancements as such, but has to be made on a case-by-case basis. Starting from the recently proposed taxation approach to cognition enhancement drugs, the author analyzes available, moderately permissive models of regulation. After a thorough analysis of relevant characteristics of methylphenidate and amphetamine, the author concludes that a moderately liberal permissive regulation of enhancement use by healthy adults might be appropriate for extended release forms of methylphenidate. However, due to their danger profile, amphetamine and instant release forms of methylphenidate should not be made readily available to healthy adults and would need to be prohibited.

  17. A theoretical study on the interaction of amphetamine and single-walled carbon nanotubes

    Science.gov (United States)

    Hafizi, Hamid; Najafi Chermahini, Alireza; Mohammadnezhad, Gholamhossein; Teimouri, Abbas

    2015-02-01

    The adsorption of 1-phenyl-2-aminopropane (amphetamine) on the (4,4), (5,5), (6,6), and (7,7) single-walled carbon nanotubes (SWCNTs) has been theoretically investigated. The molecule has been located in different modes including parallel, perpendicular, and oblique on the outer surface of carbon nanotubes. The physisorption of amphetamine onto SWCNT sidewall is thermodynamically favored; as a consequence, it modulates the electronic properties of pristine nanotube in the vicinity of Fermi region. The adsorption energies for the parallel and oblique modes found in the range of -1.13 to -1.88 and -1.27 to -2.01 kcal/mol, respectively. Projected density of states (PDOS) and frontier orbital analysis in the vicinity of Fermi level region suggest the electronic states to be contributed from SWCNT rather than amphetamine molecule.

  18. Increased amphetamine-induced locomotor activity, sensitization, and accumbal dopamine release in M5 muscarinic receptor knockout mice

    DEFF Research Database (Denmark)

    Schmidt, Lene S; Miller, Anthony D; Lester, Deranda B

    2010-01-01

    showed that M(5) receptor knockout (M (5) (-/-) ) mice are less sensitive to the reinforcing properties of addictive drugs. MATERIALS AND METHODS: Here, we investigate the role of M(5) receptors in the effects of amphetamine and cocaine on locomotor activity, locomotor sensitization, and dopamine release...... and locomotor sensitization were enhanced in M (5) (-/-) mice, while the effects of cocaine were similar in M (5) (-/-) and wild-type mice. RESULTS: Consistent with the behavioral results, amphetamine-, but not cocaine, -elicited dopamine release in nucleus accumbens was enhanced in M (5) (-/-) mice. DISCUSSION......: The different effects of amphetamine and cocaine in M (5) (-/-) mice may be due to the divergent pharmacological profile of the two drugs, where amphetamine, but not cocaine, is able to release intracellular stores of dopamine. In conclusion, we show here for the first time that amphetamine...

  19. Determination of amphetamines in hair by GC/MS after small-volume liquid extraction and microwave derivatization.

    Science.gov (United States)

    Meng, Pinjia; Zhu, Dan; He, Hongyuan; Wang, Yanyan; Guo, Fei; Zhang, Liang

    2009-09-01

    We report here on the results of a procedure for the determination of amphetamine drugs in hair. The procedure is simple and sensitive. The results from the procedure using small-volume extraction matches perfectly with those either from using the derivatization method or selected ion monitoring (SIM) detection. We validated our method using four different amine drugs, including amphetamine, methamphetamine, methylenedioxy-amphetamine and methylenedioxy-methamphetamine. The detection limit for these drugs is about 50 +/- 7.5 pg/mg in hair and the intra-day and inter-day reproducibility are within 15% at most drug concentrations. Moreover, we also showed the utility of the procedure in analyses of authentic hair samples taken from amphetamine abusers, and demonstrated that the method meets the requirement for the analysis of a trace amounts of amphetamines in human hair.

  20. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Science.gov (United States)

    de Oliveira, Lúcio Garcia; de Souza, Letícia Maria de Araújo; Barroso, Lúcia Pereira; Gouvêa, Marcela Júlio César; de Almeida, Carlos Vinícius Dias; Muñoz, Daniel Romero; Leyton, Vilma

    2015-01-01

    OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for. METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders). A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI) was defined as the measure for association. The significance level was established as p < 0.05. RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8) years, as well as low education (8.6 [SD = 2.3] years); 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69), having spent less than nine years at school (OR = 1.76), being autonomous (OR = 1.65), working night shifts or irregular schedules (OR = 2.05), working over 12 hours daily (OR = 2.14), and drinking alcohol (OR = 1.74). CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”); Law 12,619/2012) which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil. PMID:26398875

  1. Differential effects of amphetamines-induced neurotoxicity on appetitive and aversive Pavlovian conditioning in mice.

    Science.gov (United States)

    Achat-Mendes, Cindy; Ali, Syed F; Itzhak, Yossef

    2005-06-01

    The abuse of substituted amphetamines such as methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA/Ecstasy) can result in neurotoxicity, manifested as the depletion of dopamine (DA) and 5-hydroxytriptamine (5-HT; serotonin) axon terminal markers in humans and animal models. Human METH and MDMA users exhibit impairments in memory and executive functions, which may be a direct consequence of the neurotoxic potential of amphetamines. The objective of this study was to investigate the influence of amphetamines-induced neurotoxicity on Pavlovian learning. Using mouse models of selective DA neurotoxicity (METH; 5 mg/kg x 3), selective 5-HT neurotoxicity (fenfluramine /FEN; 25 mg/kg x 4) and dual DA and 5-HT neurotoxicity (MDMA; 15 mg/kg x 4), appetitive and aversive conditioning were investigated. Dopaminergic neurotoxicity significantly impaired METH and cocaine conditioned place preference (CPP), but had no effect on LiCl-induced conditioned place aversion (CPA). In contrast, serotonergic neurotoxicity significantly enhanced CPP, and had no effect on CPA. Dual dopaminergic/serotonergic neurotoxicity had no apparent effect on CPP; however, CPA was significantly attenuated. Postmortem analysis revealed that significantly diminished levels of DA and 5-HT markers persisted in the striatum, frontal cortex, hippocampus, and amygdala. These findings suggest that amphetamines-induced dopaminergic and serotonergic neurotoxicity exert opposing influences on the affective state produced by subsequent drug reward, while dual dopaminergic/serotonergic neurotoxicity impairs associative learning of aversive conditioning. Furthermore, results revealed that amphetamines-induced DA and 5-HT neurotoxicity modulates appetitive Pavlovian conditioning similar to other DA and 5-HT neurotoxins. Modulation of Pavlovian conditioning by amphetamines-induced neurotoxicity may be relevant to compulsive drug-seeking behavior in METH and MDMA abusers.

  2. Methamphetamine and amphetamine isomer concentrations in human urine following controlled Vicks VapoInhaler administration.

    Science.gov (United States)

    Smith, Michael L; Nichols, Daniel C; Underwood, Paula; Fuller, Zachary; Moser, Matthew A; Flegel, Ron; Gorelick, David A; Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-10-01

    Legitimate use of legal intranasal decongestants containing l-methamphetamine may complicate interpretation of urine drug tests positive for amphetamines. Our study hypotheses were that commonly used immunoassays would produce no false-positive results and a recently developed enantiomer-specific gas chromatography-mass spectrometry (GC-MS) procedure would find no d-amphetamine or d-methamphetamine in urine following controlled Vicks VapoInhaler administration at manufacturer's recommended doses. To evaluate these hypotheses, 22 healthy adults were each administered one dose (two inhalations in each nostril) of a Vicks VapoInhaler every 2 h for 10 h on Day 1 (six doses), followed by a single dose on Day 2. Every urine specimen was collected as an individual void for 32 h after the first dose and assayed for d- and l-amphetamines specific isomers with a GC-MS method with >99% purity of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl derivatives and 10 µg/L lower limits of quantification. No d-methamphetamine or d-amphetamine was detected in any urine specimen by GC-MS. The median l-methamphetamine maximum concentration was 62.8 µg/L (range: 11.0-1,440). Only two subjects had detectable l-amphetamine, with maximum concentrations coinciding with l-methamphetamine peak levels, and always ≤ 4% of the parent's maximum. Three commercial immunoassays for amphetamines EMIT(®) II Plus, KIMS(®) II and DRI(®) had sensitivities, specificities and efficiencies of 100, 97.8, 97.8; 100, 99.6, 99.6 and 100, 100, 100%, respectively. The immunoassays had high efficiencies, but our first hypothesis was not affirmed. The EMIT(®) II Plus assay produced 2.2% false-positive results, requiring an enantiomer-specific confirmation.

  3. Combination effects of amphetamines under hyperthermia - the role played by oxidative stress.

    Science.gov (United States)

    da Silva, Diana Dias; Silva, Elisabete; Carmo, Helena

    2014-06-01

    Rise in body temperature is a life-threatening consequence of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) abuse. We evaluated the impact of hyperthermia on the cytotoxicity of combinations of MDMA and three other amphetamines, often co-ingested. For this, Hep G2 cells were exposed to MDMA, d-amphetamine, methamphetamine and 4-methylthioamphetamine, individually or combined, at 40.5 °C. The results were compared with normothermia data (37.0 °C). Mixture additivity expectations were calculated by independent action and concentration addition (CA) models. To delineate the mechanism(s) underlying the elicited effects, a range of stress endpoints was evaluated, including quantification of reactive oxygen/nitrogen species (ROS/RNS), lipid peroxidation, reduced/oxidized glutathione (GSH/GSSG), ATP and mitochondrial membrane potential (Δψm) changes. Our data show that, in hyperthermia, amphetamines acted additively and mixture effects were accurately predicted by CA. At 40.5 °C, even slight increases in the concentrations of each drug/mixture promoted significant rises in cytotoxicity, which quickly shifted from roughly undetectable to maximal mortality. Additionally, the increase of RNS/ROS production, decrease of GSH, ATP depletion and mitochondrial impairment were exacerbated under hyperthermia. Importantly, when equieffective cytotoxic concentrations of the mixture and individual amphetamines were compared for all tested stress endpoints, mixture effects did not deviate from those elicited by individual treatments, suggesting that these amphetamines have a similar mode of action, which is not altered in combination. Concluding, our data indicate that amphetamine mixtures produce deleterious effects, even when individual drugs are combined at negligible concentrations. These effects are strongly exacerbated in hyperthermia, emphasizing the potential increased risks of ecstasy intake, especially when hyperthermia occurs concurrently with polydrug abuse.

  4. Occupational conditions and the risk of the use of amphetamines by truck drivers

    Directory of Open Access Journals (Sweden)

    Lúcio Garcia de Oliveira

    2015-01-01

    Full Text Available OBJECTIVE To test whether the occupational conditions of professional truck drivers are associated with amphetamine use after demographic characteristics and ones regarding mental health and drug use are controlled for.METHODS Cross-sectional study, with a non-probabilistic sample of 684 male truck drivers, which was collected in three highways in Sao Paulo between years 2012 and 2013. Demographic and occupational information was collected, as well as data on drug use and mental health (sleep quality, emotional stress, and psychiatric disorders. A logistic regression model was developed to identify factors associated with amphetamine use. Odds ratio (OR; 95%CI was defined as the measure for association. The significance level was established as p < 0.05.RESULTS The studied sample was found to have an average age of 36.7 (SD = 7.8 years, as well as low education (8.6 [SD = 2.3] years; 29.0% of drivers reported having used amphetamines within the twelve months prior to their interviews. After demographic and occupational variables had been controlled for, the factors which indicated amphetamine use among truck drivers were the following: being younger than 38 years (OR = 3.69, having spent less than nine years at school (OR = 1.76, being autonomous (OR = 1.65, working night shifts or irregular schedules (OR = 2.05, working over 12 hours daily (OR = 2.14, and drinking alcohol (OR = 1.74.CONCLUSIONS Occupational aspects are closely related to amphetamine use among truck drivers, which reinforces the importance of closely following the application of law (Resting Act (“Lei do Descanso”; Law 12,619/2012 which regulates the workload and hours of those professionals. Our results show the need for increased strictness on the trade and prescription of amphetamines in Brazil.

  5. Sulfur compounds in therapy: Radiation-protective agents, amphetamines, and mucopolysaccharide sulfation

    Energy Technology Data Exchange (ETDEWEB)

    Foye, W.O. (Massachusetts College of Pharmacy and Allied Health Sciences, Boston (United States))

    1992-09-01

    Sulfur-containing compounds have been used in the search for whole-body radiation-protective compounds, in the design of amphetamine derivatives that retain appetite-suppressive effects but lack most behavioral effects characteristic of amphetamines, and in the search for the cause of kidney stone formation in recurrently stoneforming patients. Organic synthetic procedures were used to prepare radiation-protective compounds having a variety of sulfur-containing functional groups, and to prepare amphetamine derivatives having electron-attracting sulfur functions. In the case of the kidney stone causation research, isolation of urinary mucopolysaccharides (MPS) from recurrently stoneforming patients was carried out and the extent of sulfation of the MPS was determined by electrophoresis. Whole-body radiation-protective agents with a high degree of protection against lethal doses of gamma-radiation in mice were found in a series of quinolinium and pyridinium bis(methylthio) and methylthio amino derivatives. Mechanism studies showed that the copper complexes of these agents mimicked the beneficial action of superoxide dismutase. Electron-attracting sulfur-containing functions on amphetamine nitrogen, as well as 4'-amino nitrogen provided amphetamine derivatives with good appetite-suppressant effects and few or no adverse behavioral effects. Higher than normal levels of sulfation of the urinary MPS of stone formers suggested a cause for recurrent kidney stone formation. A sulfation inhibitor was found to prevent recurrence of stone formation and inhibit growth of existing stones. The inclusion of various sulfur-containing functions in organic molecules yielded compounds having whole-body radiation protection from lethal doses of gamma-radiation in animals. The presence of electron-attracting sulfur functions in amphetamine gave derivatives that retained appetite-suppressant effects and eliminated most adverse behavioral effects.

  6. Amphetamine administration improves neurochemical outcome of lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dhillon, H S; Dose, J M; Prasad, R M

    1998-09-07

    This study examined the effects of the administration of D-amphetamine on the regional accumulation of lactate and free fatty acids (FFAs) after lateral fluid percussion (FP) brain injury in the rat. Rats were subjected to either FP brain injury of moderate severity (1.9 to 2.0 atm) or sham operation. At 5 min after injury, rats were treated with either d-amphetamine (4 mg/kg, i.p.) or saline. At 30 min and 60 min after brain injury, brains were frozen in situ, and cortices and hippocampi were excised at 0 degrees C. In the saline-treated brain injured rats, levels of lactate were increased in the ipsilateral left cortex and hippocampus at 30 min and 60 min after injury. These increases were attenuated by the administration of D-amphetamine at 5 min after lateral FP brain injury. At 30 and 60 min after FP brain injury, increases in the levels of all individual FFAs (palmitic, stearic, oleic and arachidonic acids) and of total FFAs were also observed in the ipsilateral cortex of the saline-treated injured rats. These increases in the ipsilateral cortex and hippocampus were also attenuated by the administration of d-amphetamine. Neither levels of lactate nor levels of FFAs were increased in the contralateral cortex in the saline-treated injured rats at 30 min or 60 min after FP brain injury. The levels of lactate and FFAs in the contralateral cortex were also unaffected by the administration of D-amphetamine. These results suggest that the attenuation of increases in the levels of lactate and FFAs in the ipsilateral cortex and hippocampus may be involved in the amphetamine-induced improvement in behavioral outcome after lateral FP brain injury.

  7. Amphetamine margin in sports. [Effects on performance of highly trained athletes

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1980-01-01

    The amphetamines can enhance athletic performance. That much seems clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both man and rat. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogues of such performance have also been used and similar enhancement demonstrated. The amount of change induced by the amphetamines is usually small, of the order of a few percent. Nevertheless, since a fraction of a percent improvement can make the difference between fame and oblivion, the margin conferred by these drugs can be quite important.

  8. Prepulse inhibition of the acoustic startle reflex in pigs and its disruption by d-amphetamine

    DEFF Research Database (Denmark)

    Lind, Nanna Marie; Arnfred, Sidse M; Hemmingsen, Ralf P;

    2004-01-01

    for validation of a pig model of psychosis, we wished to verify the existence of PPI in landrace pigs and investigate the potential disruption of PPI by d-amphetamine (AMPH) in these animals. PPI of the acoustic startle reflex and its potential disruption by AMPH were investigated using three doses 0.5-1.5mg...... and, in spite of only the 0.5mg/kg dose proved statistically significant, the results indicate this to be dose-related. We have demonstrated the phenomenon of PPI of the startle reflex in landrace pigs and its disruption by d-amphetamine. Studies of sensorimotor gating defects could be a valuable...

  9. Amphetamines as potential inducers of fatalities: a review in the district of Ghent from 1976-2004.

    Science.gov (United States)

    De Letter, Els A; Piette, Michel H A; Lambert, Willy E; Cordonnier, Jan A C M

    2006-01-01

    Abuse of amphetamine (AMP) and its derivatives, such as 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy'), 3,4-methylenedioxyethylamphetamine (MDEA, MDE), and 3,4-methylenedioxyamphetamine (MDA) is an important public issue. Fatalities following ingestion of these substances are not infrequent in current forensic practice. The aim of this study was twofold. Firstly, considering the wide range of blood levels reported in fatalities, to provide insight into the interpretation of a quantified blood level and, secondly, to examine and discuss possible causes, mechanisms and manners of death. All the medico-legal files between January 1976 and December 2004 were skimmed through to investigate whether amphetamine and/or derivatives were involved in the fatal outcome. Particularly, in addition to overdose cases due to or including amphetamines, all amphetamines-related fatalities were examined. In addition to AMP, MDMA, MDEA, and MDA, two other amphetamine derivatives, namely 4-methylthioamphetamine (4-MTA) and para-methoxyamphetamine (PMA) were considered. In 34 fatalities, amphetamines were involved and the majority were men, under the age of 25 years. A wide range of blood levels was found: e.g. MDMA blood concentrations in cases of 'pure' intoxication were found between 0.27 and 13.51 microg/ml. The age and sex distribution as well as the broad range of quantified amphetamines blood levels were in line with those reported in the literature. In our study group, 'pure' intoxications with amphetamines, polydrug overdoses, and the combination of amphetamines use and polytrauma were the most prominent causes of death. Considering the manner of death in these fatalities, unintentional overdoses were most frequent, though suicides, traffic accidents, and criminal offences associated with amphetamines use also accounted for significant percentages. Acute to subacute cardiopulmonary failure was the most frequent mechanism of death, followed by (poly)trauma, mechanical

  10. Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

    Science.gov (United States)

    Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

    Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

  11. Simulated Driving Changes in Young Adults with ADHD Receiving Mixed Amphetamine Salts Extended Release and Atomoxetine

    Science.gov (United States)

    Kay, Gary G.; Michaels, M. Alex; Pakull, Barton

    2009-01-01

    Background: Psychostimulant treatment may improve simulated driving performance in young adults with attention-deficit/hyperactivity disorder (ADHD). Method: This was a randomized, double-blind, placebo-controlled, crossover study of simulated driving performance with mixed amphetamine salts--extended release (MAS XR) 50 mg/day (Cohort 1) and…

  12. Membrane permeable C-terminal dopamine transporter peptides attenuate amphetamine-evoked dopamine release

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Owens, WA; Winkler, Marie-Therese

    2013-01-01

    The dopamine transporter (DAT) is responsible for sequestration of extracellular dopamine (DA). The psychostimulant amphetamine (AMPH) is a DAT substrate, which is actively transported into the nerve terminal, eliciting vesicular depletion and reversal of DA transport via DAT. Here, we investigate...

  13. Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux

    DEFF Research Database (Denmark)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica

    2008-01-01

    of the dopamine (DA) transporter (DAT) as the site of direct interaction with SYN1A. Amphetamine (AMPH) increases the association of SYN1A with human DAT (hDAT) in a heterologous expression system (hDAT cells) and with native DAT in murine striatal synaptosomes. Immunoprecipitation of DAT from the biotinylated...

  14. Simultaneous Determination of Heroin, Amphetamine and their Basic Impurities and Adulterants Using Microemulsion Electrokinetic Chromatography

    Institute of Scientific and Technical Information of China (English)

    Tao WEN; Xia ZHAO; Guo An LUO; Jian WANG; Yi Ming WANG; Pan LI; Jun ZHU; Zhong Shang YU

    2005-01-01

    Simultaneous separation of 17 species of heroin, amphetamine and their basic impurities and adulterants was conducted within 10 minutes by using capillary microemulsion electrokinetic chromatography. The influences of pH and 1-butanol cosurfactant on the separation were investigated, and 1-butanol was found to be a principal factor to improve separation efficiency.

  15. Effects of mescaline and amphetamine on simultaneous visual discrimination in two inbred strains of mice.

    Science.gov (United States)

    Castellano, C

    1979-03-29

    The effects of mescaline and amphetamine were investigated in BALB/cJ (BALB) and C57BL/6J (C57) mice using the five-choice Yerkes--Thompson Bryant--Bovet-Nitti apparatus for patterns discrimination. Two sets of experiments were carried out. In the first set, pretrial administration of mescaline (5, 10, and 20 mg/kg) was followed by performance improvements in the C57 mice, while performances of the BALB strain were impaired by the treatment, as compared with those of the saline-injected (4 ml/kg) controls. The pretrial administration of amphetamine (0.1, 0.25, and 0.5 mg/kg) improved performances of both strains. In a second set of experiments, the same effects as in the pretrial experiments were observed in both strains following administration of mescaline (20 mg/kg) and amphetamine (0.5 mg/kg) immediately after each experimental session. No effect was evident when the drugs were injected 2 h after training, suggesting that effects of the pretrial treatments were due to influences of mescaline and amphetamine on the consolidation processes of the two strains of mice tested.

  16. Cross-reactivity of amphetamine analogues with Roche Abuscreen radioimmunoassay reagents

    Energy Technology Data Exchange (ETDEWEB)

    Cody, J.T. (Air Force Drug Testing Laboratory, Brooks AFB, TX (USA))

    1990-01-01

    Cross-reactivity of amphetamine analogues with the Abuscreen amphetamine radioimmunoassay reagents was determined for both the standard and high specificity antibody systems. Compounds tested included 2-methoxyamphetamine, 4-hydroxymethamphetamine, 2,5-dimethoxyamphetamine (DMA), 4-bromo-2,5-dimethoxyamphetamine (DOB), 4-bromo-2,5-dimethoxy-beta-phenethylamine (BDMPEA), 3,4,5-trimethoxyamphetamine (TMA), 3,4-methylenedioxyamphetamine (MDA), N,N-dimethyl-3,4-methylenedioxyamphetamine and N-hydroxy-3,4-methylenedioxyamphetamine (N-OH MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), 2,5-dimethoxy-4-ethylamphetamine, 2,5-dimethoxy-4-methylamphetamine (DOM), and 3,4,5-trimethoxyphenethylamine (mescaline). Blank negative reference material was spiked with 1,000 to 100,000 ng/mL of the amphetamine analogue and used as sample in the assays. MDA was the only analogue that showed cross reactivity equal to or greater than that of amphetamine. None of the other analogue compounds demonstrated a positive result at even the highest concentration; however several showed depressed counts at various concentration levels.

  17. Reduced preabsorptive insulin response in aged rats : differential effects of amphetamine and arginine-vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Strubbe, J.H.; Bohus, B.

    1991-01-01

    The experiments presented here have been designed to investigate whether the age-related attenuation of the vagal reactivity to emotional stressors and its modulation by amphetamine (Amph) or arginine-vasopressin (AVP) can be generalized for other physiological response patterns. We therefore studie

  18. Effectiveness of Hope Therapy Protocol on Depression and Hope in Amphetamine Users

    Directory of Open Access Journals (Sweden)

    Sadeghi

    2015-12-01

    Full Text Available Background Addiction has surpassed the boundaries of health and treatment and turned into a social crisis and a debilitating and major concern in today’s world. Amphetamine, one of the addictive drugs, is classified as psycho-stimulants drugs, which increase arousal, alertness, and motor activity. Humans report that this drug produces a significant euphoria and is highly addictive. Objectives The present study aimed to evaluate the effectiveness of hope therapy protocol (HTP on depression reduction and hope increase in amphetamine users. Patients and Methods This study has a quasi-experimental design with experimental and control groups. The sample included all amphetamine consumers referring to day drug addiction treatment center in Ray City, Iran, selected with convenience method. In order to analyze the data, multivariate analysis of covariance (MANCOVA was applied using SPSS software. Results The results showed that F value of mean scores in depression and hope post-tests of the experimental and control groups are 24.94 and 25.73, respectively, which are significant (P < 0.01. Therefore, hope therapy training could reduce depressive symptoms in amphetamine consumers and improve their hope. Conclusions Performing HTP can improve hopefulness and symptoms of patients, specially addicted ones. In addition, it can prevent substance abusers from returning to drugs and leaving the treatment period unfinished.

  19. Amphetamines in wastewater of the city Poznań (Poland)--estimation of drug abuse.

    Science.gov (United States)

    Nowicki, Piotr; Klos, Jolanta; Kokot, Zenon J

    2014-01-01

    The aim of the study was to determine the profile of amphetamines consumed by a community in Poland. Amphetamine, methamphetamine and MDMA (ecstasy) were detected in wastewater samples collected from the main Wastewater Treatment Plant in the city of Poznań (about 687 000 people) using liquid chromatography/tandem mass spectrometry (LC-MS-MS). Back-calculations used in the sewage epidemiology approach were applied to estimate the level of consumption of the drugs being analyzed. These types of studies were carried out for the first time in Poland for a considerable period--from June 2009 to December 2010. The analysis of variance (ANOVA) confirmed significant monthly differences in amphetamine consumption. The concentration of amphetamine, methamphetamine and MDMA in wastewater samples and the levels of their consumption were lower than reported in other European countries, but unexpectedly, the ratio of consumed methamphetamine to MDMA and the consumption level of methamphetamine were relatively high. This study shows that sewage epidemiology is a promising tool, especially when combined with classical methods, to estimate illicit drugs use in a particular population. Therefore, efforts should be made to monitor the profiles and consumption levels of drugs and to extend the scope of the research to other illicit substances, especially cannabinoids and cocaine.

  20. [Cardiogenic shock after ingestion of amphetamines on a ground of Mycoplasma myocarditis].

    Science.gov (United States)

    Berger, K; Hérault, M-C; Danel, V; Vincent, F; Jacquot, C

    2008-03-01

    Amphetamines are considered as narcotics in France. Their use induces modifications of the central nervous system and of the cardiovascular, respiratory and urinary systems by a sympathomimetic indirect effect. Here is reported the observation of a young woman who absorbed amphetamines causing a cardiogenic shock on a ground of acute myocarditis. The constitution of haemodynamic, respiratory and neurologic distresses lead to the endotracheal intubation of the patient. The haemodynamic status remaining shaky, despite the use of vasoactive drugs, a circulatory assistance by intra-aortic counter pulsation balloon was carried out. The initial echocardiography showed a left ventricular ejection fraction lower than 20%. Amphetamine's toxicity mechanisms still remain complicated; on cardiovascular plan, some cases of coronary artery spasm have been described. The coronarography, not accomplished immediately, was normal. Toxicological samples revealed an abnormally high amphetamines concentration. The severity of the cardiac attack was amplified by a Mycoplasma pneumoniae myocarditis. There was a positive evolution in eight days. Intoxication and infection can difficultly be dissociated in this case of cardiogenic shock.

  1. Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines.

    Science.gov (United States)

    McBride, Shawna M; Culver, Bruce; Flynn, Francis W

    2008-09-01

    This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6-8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors.

  2. Acceleration of cardiovascular-biological age by amphetamine exposure is a power function of chronological age

    Science.gov (United States)

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed. Methods Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined. Results The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both pamphetamine exposure persisted after adjustment for all known cardiovascular risk factors (pamphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process. PMID:28243315

  3. Roche DAT immunoassay: sensitivity and specificity testing for amphetamines, cocaine, and opiates in oral fluid.

    Science.gov (United States)

    Crooks, C Richard; Brown, Sue

    2010-03-01

    Laboratory testing of oral fluid for drugs of abuse continues to expand in the workplace, legal, treatment, and health settings. In this study, we assessed recently developed homogeneous Roche DAT screening assays for amphetamines, cocaine metabolite [benzoylecgonine (BZE)], methamphetamines, and opiates in oral fluid. Precision and accuracy were assessed using control samples at +/-25% of cutoff. Sensitivity, specificity, and agreement compared to liquid chromatography-tandem mass spectrometry (LC-MS-MS) was assessed by analysis of oral fluid specimens collected from 994 subjects enrolled in a drug treatment or probation and parole drug-testing program. An additional 180 research specimens from Kroll Laboratories were analyzed for amphetamine and methamphetamine. Screening cutoff concentrations (ng/mL) were as follows: amphetamines, 40; cocaine metabolite, 3; methamphetamines, 40; and opiates, 10. LC-MS-MS analyses were performed with the following cutoff concentrations (ng/mL): amphetamine, 40; BZE, 2.0; methamphetamine, 40; and codeine or morphine, 10. The percent coefficient of variation ranged from 3.4% to 7.3%. Sensitivity and specificity of the Roche DAT assays compared to LC-MS-MS were > 94%, and agreement was > 96% for the four assays. The performance of the Roche DAT assays suggests these new homogeneous screening assays will be an attractive alternative to existing more labor-intensive enzyme immunoassays.

  4. Methylphenidate and Amphetamine Do Not Induce Cytogenetic Damage in Lymphocytes of Children with ADHD

    Science.gov (United States)

    Witt, Kristine L.; Shelby, Michael D.; Itchon-Ramos, Nilda; Faircloth, Melissa; Kissling, Grace E.; Chrisman, Allan K.; Ravi, Hima; Murli, Hemalatha; Mattison, Donald R.; Kollins, Scott H.

    2008-01-01

    The inducement of chromosomal damage in lymphocytes among children with attention deficit hyperactivity disorder receiving treatment with methylphenidate- or amphetamine-based drugs is investigated. Findings did not reveal significant increases in cytogenetic damage related to the treatment. The risk for cytogenetic damage posed by such products…

  5. Brain injury associated with widely abused amphetamines: neuroinflammation, neurogenesis and blood-brain barrier.

    Science.gov (United States)

    Silva, Ana P; Martins, Tânia; Baptista, Sofia; Gonçalves, Joana; Agasse, Fabienne; Malva, João O

    2010-12-01

    Over the course of the 20(th) century, it became increasingly clear that amphetamine-like psychostimulants carried serious abuse liability that has resulted in sociological use patterns that have been described as epidemics. In fact, drug addiction is a brain disease with a high worldwide prevalence, and is considered the most expensive of the neuropsychiatric disorders. This review goes beyond the previously well-documented evidence demonstrating that amphetamines cause neuronal injury. Cellular and molecular mechanisms involved in the neurotoxicity of psychostimulants drugs have been extensively described giving particular attention to the role of oxidative stress and metabolic compromise. Recently, it was shown that the amphetamine class of drugs of abuse triggers an inflammatory process, emerging as a critical concept to understand the toxic effects of these drugs. Moreover, it has been suggested that psychostimulants compromise the capacity of the brain to generate new neurons (neurogenesis), and can also lead to blood-brain barrier (BBB) dysfunction. Together, these effects may contribute to brain damage, allowing the entry of pathogens into the brain parenchyma and thus decreasing the endogenous brain repair resources. The overall objective of this review is to highlight experimental evidence in an attempt to clarify the role of neuroinflammation in amphetamines-induced brain dysfunction and the effect of these drugs on both neurogenesis and BBB integrity.

  6. Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water

    Energy Technology Data Exchange (ETDEWEB)

    Brause, R. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Fricke, H. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Gerhards, M. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Weinkauf, R. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany); Kleinermanns, K. [Institut fuer Physikalische Chemie, Heinrich-Heine-Universitaet, Universitaetsstrasse 1, D-40225 Duesseldorf (Germany)], E-mail: kleinermanns@uni-duesseldorf.de

    2006-08-21

    In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine-(H{sub 2}O){sub 1,2} complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S{sub 0} {sup {yields}} S{sub 1} transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine-(H{sub 2}O){sub 1,2} are tentatively assigned.

  7. Determination of amphetamines in hair by integrating sample disruption, clean-up and solid phase derivatization.

    Science.gov (United States)

    Argente-García, A; Moliner-Martínez, Y; Campíns-Falcó, P; Verdú-Andrés, J; Herráez-Hernández, R

    2016-05-20

    The utility of matrix solid phase dispersion (MSPD) for the direct analysis of amphetamines in hair samples has been evaluated, using liquid chromatography (LC) with fluorescence detection and precolumn derivatization. The proposed approach is based on the employment of MSPD for matrix disruption and clean-up, followed by the derivatization of the analytes onto the dispersant-sample blend. The fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) has been used for derivatization. Different conditions for MSPD, analyte purification and solid phase derivatization have been tested, using amphetamine (AMP), methamphetamine (MET), ephedrine (EPE) and 3,4-methylenedioxymethamphetamine (MDMA) as model compounds. The results have been compared with those achieved by using ultrasound-assisted alkaline digestion and by MSPD combined with conventional solution derivatization. On the basis of the results obtained, a methodology is proposed for the analysis of amphetamines in hair which integrates sample disruption, clean-up and derivatization using a C18 phase. Improved sensitivity is achieved with respect to that obtained by the alkaline digestion or by the MSPD followed by solution derivatization methods. The method can be used for the quantification of the tested amphetamines within the 2.0-20.0ng/mg concentration interval, with limits of detection (LODs) of 0.25-0.75ng/mg. The methodology is very simple and rapid (the preparation of the sample takes less than 15min).

  8. [The detection of amphetamines in urine samples using immunochromatographic test strips].

    Science.gov (United States)

    Shanin, I A; Khan, O Iu; Petukhov, A E; Smirnov, A V; Eremin, S A

    2012-01-01

    This study has demonstrated the possibility of using immunochromatographic test strips for the reliable qualitative detection of amphetamine and methamphetamine in the urine samples at a cut-off level of 300 ng/ml. The test strips obtained from different manufactures are shown to be slightly different in terms of specificity as appears from the frequency of cross-reactions with various pharmaceutical products and narcotic drugs. Also, the use of the immunochromatographic strips makes it possible to determine amphetamine in a range of concentrations from 100 to 1000 ng/ml by measuring the intensity of test-line colour with the help of a TotalLab TL120 programmer and special scanning programs. The analysis for amphetamine using the NrcoStop (Osiris S) immunochromatographic strips failed to confirm the presence of this substance in the urine samples from the subjects who had drunk 0.5 l of energy drinks, such as Adrenaline RUSH, Red Bull, and Burn. It means that the presence of amphetamine in the urine should not be attributed to the consumption of such drinks.

  9. [Application of solid-phase microextraction technique to the detection of amphetamines in urine by GC].

    Science.gov (United States)

    Liu, W; Shen, M

    1999-05-01

    A simple and rapid detection of nine amphetamines co-existing in urine was described. In the test, the method of solid-phase micro-extraction (SPME) by GC technique was used. Urine (1.0 ml), NaCl (0.3 g) and 4-phenylbutylamine (internal standard) were added into a vial (1.5 ml), then the sample was adjusted to pH 12 with 10% NaOH and sealed with a teflon-coated septum. After immersion of the SPME fiber (100 PDME) in the sample for 15 min, the SPME needle was inserted into the injection port of the GC and extruded for 3 min. The result showed that each peak from nine amphetamines compounds and internal standard was clearly separated. The calibration curves were linear from 0.2 to 15 micrograms/ml for most of five amphetamines with r between 0.9928-0.9995. The CV were less 10%. It is concluded that the method is simple, quick, accurate and useful for the practical detection of urine concentration of amphetamines.

  10. Performance of immunoassays in screening for opiates, cannabinoids and amphetamines in post-mortem blood.

    Science.gov (United States)

    Hino, Yukiko; Ojanperä, Ilkka; Rasanen, Ilpo; Vuori, Erkki

    2003-01-28

    Several immunoassay methods for screening of abused drugs in whole blood were evaluated in post-mortem forensic toxicology. Blood samples known to be positive or negative for opiates, cannabinoids or amphetamines by gas chromatography-mass spectrometry (GC-MS) were analysed by EMIT II Plus and EMIT d.a.u., Syva RapidTest and Triage 8 after acetone precipitation. In these experiments, the EMIT immunoassay method was modified by using the Dade Behring VIVA analyser to detect substances more sensitively. Low concentrations of abused drugs were detected in blood samples. The sensitivities of the modified EMIT method for opiates, cannabinoids and amphetamines were 100, 86 and 98%, respectively, whereas the values were below 86% with the other methods. The specificities of all immunoassay methods for opiates and cannabinoids were 83% or above but 51-85% for amphetamines. Sample rejection occurred in a few cases with the EMIT amphetamine assays. The modified EMIT immunoassay system presented here seems to be useful for screening of drugs of abuse in post-mortem blood samples, especially when urine is not available.

  11. Acute but not delayed amphetamine treatment improves behavioral outcome in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, Karsten; Kristiansen, Uffe;

    2011-01-01

    OBJECTIVES: The objective of this study was to examine the effects of d-amphetamine (amph) upon recovery after embolic stroke in rats. METHODS: Ninety-three rats were embolized in the right middle cerebral artery and assigned to: (1) controls; (2) combination (acute amph and later amph-facilitate...

  12. Double resonance spectroscopy of different conformers of the neurotransmitter amphetamine and its clusters with water

    Science.gov (United States)

    Brause, R.; Fricke, H.; Gerhards, M.; Weinkauf, R.; Kleinermanns, K.

    2006-08-01

    In this paper the conformational landscape of amphetamine in the neutral ground state is examined by both spectroscopy and theory. Several spectroscopic methods are used: laser-induced fluorescence (LIF), resonance-enhanced two-photon ionization (R2PI), dispersed fluorescence and IR/R2PI hole burning spectroscopy. The latter two methods provide for the first time vibrationally resolved spectra of the neutral ground state of dl-amphetamine and the amphetamine-(H 2O) 1,2 complexes. Nine stable conformers of the monomer were found by DFT (B3LYP/6-311++G(d,p)) and ab initio (MP2/6-311++G(d,p)) calculations. For conformer analysis the vibrations observed in the IR/R2PI hole burning and dispersed fluorescence spectra obtained from single vibronic levels (SVLF) of a selected conformer were compared with the results of an ab initio normal mode analysis. By this procedure three S 0 → S 1 transitions in the R2PI spectrum were assigned to three different conformer structures. Another weak transition earlier attributed to another conformer could be assigned to a vibronic band of one of the three conformers. Furthermore spectra of amphetamine-(H 2O) 1,2 are tentatively assigned.

  13. Electrochemical oxidation of amphetamine-like drugs and application to electroanalysis of ecstasy in human serum.

    Science.gov (United States)

    Garrido, E M P J; Garrido, J M P J; Milhazes, N; Borges, F; Oliveira-Brett, A M

    2010-08-01

    Amphetamine and amphetamine-like drugs are popular recreational drugs of abuse because they are powerful stimulants of the central nervous system. Due to a dramatic increase in the abuse of methylenedioxylated derivatives, individually and/or in a mixture, and to the incoherent and contradictory interpretation of the electrochemical data available on this subject, a comprehensive study of the redox properties of amphetamine-like drugs was accomplished. The oxidative behaviour of amphetamine (A), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) was studied in different buffer systems by cyclic, differential pulse and square-wave voltammetry using a glassy carbon electrode. A quantitative electroanalytical method was developed and successfully applied to the determination of MDMA in seized samples and in human serum. Validation parameters, such as sensitivity, precision and accuracy, were evaluated. The results found using the developed electroanalytical methodology enabled to gather some information about the content and amount of MDMA present in ecstasy tablets found in Portugal. Moreover, the data found in this study outlook the possibility of using the voltammetric methods to investigate the potential harmful effects of interaction between drugs such as MDMA and methamphetamine and other substances often used together in ecstasy tablets.

  14. Amphetamine and pseudoephedrine cross-tolerance measured by c-Fos protein expression in brains of chronically treated rats

    Directory of Open Access Journals (Sweden)

    Casalotti Stefano O

    2008-10-01

    Full Text Available Abstract Background Pseudoephedrine is a drug commonly prescribed as a nasal decongestant and bronchodilator and is also freely available in cold remedies and medications. The structural and pharmacological similarity of pseudoephedrine to amphetamine has led to evaluation of its psychomotor stimulant properties within the central nervous system. Previous investigations have shown that the acute responses to pseudoephedrine were similar to those of amphetamine and other psychostimulants. Results This study examined the effect of chronic administration of pseudoephedrine in rat nucleus accumbens and striatum and identified three further similarities to amphetamine. (i Chronic exposure to pseudoephedrine reduced the c-Fos response to acute pseudoephedrine treatment suggesting that pseudoephedrine induced tolerance in the animals. (ii In animals chronically treated with amphetamine or pseudoephedrine the acute c-Fos response to pseudoephedrine and amphetamine was reduced respectively as compared to naïve animals indicating cross-tolerance for the two drugs. (iiiThe known involvement of the dopamine system in the response to amphetamine and pseudoephedrine was further confirmed in this study by demonstrating that pseudoephedrine similarly to amphetamine, but with lower potency, inhibited [3H]dopamine uptake in synaptosomal preparations. Conclusion This work has demonstrated further similarities of the effect of pseudoephedrine to those of amphetamine in brain areas known to be associated with drug addiction. The most significant result presented here is the cross tolerance effect of amphetamine and psudoephedrine. This suggests that both drugs induce similar mechanisms of action in the brain. Further studies are required to establish whether despite its considerable lower potency, pseudoephedrine could pose health and addiction risks in humans similar to that of known psychostimulants.

  15. Elucidating the sorption mechanism of “mixed-mode” SPME using the basic drug amphetamine as a model compound

    Energy Technology Data Exchange (ETDEWEB)

    Peltenburg, Hester, E-mail: H.Peltenburg@uu.nl [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands); Groothuis, Floris A.; Droge, Steven T.J. [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands); Bosman, Ingrid J. [Netherlands Forensic Institute, P.O. Box 24044, 2490 AA The Hague (Netherlands); Hermens, Joop L.M. [Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht (Netherlands)

    2013-06-11

    Graphical abstract: -- Highlights: •C18/propylsulfonic acid “mixed-mode” SPME fiber is efficient in sampling amphetamine. •Both protonated and neutral species of amphetamine sorb to the mixed-mode fiber. •Sorption of organic cations to this mixed-mode fiber depends on pH and salinity. •Amphetamine has a 20× higher affinity to the mixed-mode coating than to polyacrylate. -- Abstract: We studied the sorption of amphetamine as a model drug to represent small, polar organic cations to a new SPME coating combining C18 and propylsulfonic acid. This combination of hydrophobic and strong cation exchange (SCX) groups was compared to conventional SPME fibers with polyacrylate (PA) or C18 coating. The affinity of amphetamine at physiological pH (PBS) was 20 to 180 times greater for the new C18/SCX coating than for C18 alone and PA of different coating thickness. As amphetamine is a base and >99% protonated at physiological pH, this enhanced affinity is attributed to the ion-exchange phase in the coating. Tests at pH above the pK{sub a} of amphetamine show that, when normalized to the coating volume, neutral amphetamine also has a higher affinity compared to PA. As ion-exchange groups are not unlimitedly present in the coating, amphetamine isotherms level off to a saturation concentration on the C18/SCX fiber at the highest tested aqueous concentrations. Also, other cations (Na{sup +}, K{sup +}, Ca{sup 2+}) compete for the SCX sites and decrease the sorption coefficients, e.g. by 1.7 log units when comparing Milli-Q water with PBS. The C18/SCX fiber provides improved sensitivity over some of the classic SPME fibers. However, care should be taken near the cation exchange capacity of the fiber and the fiber should be calibrated in an appropriate matrix so as to eliminate competition effects.

  16. β-Methylphenylethylamines: common fragmentation pathways with amphetamines in electrospray ionization collision-induced dissociation.

    Science.gov (United States)

    Brown, David H; Hansson, Robert; Oosthuizen, Francois; Sumner, Nathan

    2016-01-01

    β-Methylphenylethylamines are positional isomers of amphetamines and have been discovered in sporting supplements. Although the fragmentation of the β-methylphenylethylamine and N-methyl-β-methylphenylethylamine in gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) systems is significantly different to their amphetamine and methylamphetamine isomers, under electrospray ionization commonly used in liquid chromatography-mass spectrometry (LC-MS) systems, the fragmentation of each of the isomeric pairs is almost identical. The similarities in fragmentation make it possible for the misidentification of the β-methylphenylethylamines as the illicit amphetamines. It is proposed that the similarities are due to a fragmentation pathway involving a common phenonium ion intermediate. By careful control of fragmentation energies in liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems and/or close examination of the relative abundances of product ions formed by collision-induced dissociation (qualifier ratios), it is possible to distinguish the β-methylphenylethylamines from the amphetamines, even if significant retention time separation is not achieved. In liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF) systems the mass spectra of the β-methylphenylethylamines are identical to their amphetamine isomers. In such systems, retention time separation of the isomers is critical to avoid misidentification. During this study β-methylphenylethylamine and N-methyl-β-methylphenylethylamine have been identified in commercially available sporting supplements and oral fluid samples taken during the course of road-side drugs-in-drivers and workplace testing programmes. Copyright © 2015 John Wiley & Sons, Ltd.

  17. Amphetamines, atomoxetine and the risk of serious cardiovascular events in adults.

    Directory of Open Access Journals (Sweden)

    Hedi Schelleman

    Full Text Available MAIN OBJECTIVE: To compare the incidence rates of serious cardiovascular events in adult initiators of amphetamines or atomoxetine to rates in non-users. METHODS: This was a retrospective cohort study of new amphetamines (n=38,586 or atomoxetine (n=20,995 users. Each medication user was matched to up to four non-users on age, gender, data source, and state (n=238,183. The following events were primary outcomes of interest 1 sudden death or ventricular arrhythmia, 2 stroke, 3 myocardial infarction, 4 a composite endpoint of stroke or myocardial infarction. Cox proportional hazard regression was used to calculate propensity-adjusted hazard ratios for amphetamines versus matched non-users and atomoxetine versus matched non-users, with intracluster dependence within matched sets accounted for using a robust sandwich estimator. RESULTS: The propensity-score adjusted hazard ratio for amphetamines use versus non-use was 1.18 (95% CI: 0.55-2.54 for sudden death/ventricular arrhythmia, 0.80 (95% CI: 0.44-1.47 for stroke, 0.75 (95% CI: 0.42-1.35 for myocardial infarction, and 0.78 (95% CI: 0.51-1.19 for stroke/myocardial infarction. The propensity-score adjusted hazard ratio for atomoxetine use versus non-use was 0.41 (95% CI: 0.10-1.75 for sudden death/ventricular arrhythmia, 1.30 (95% CI: 0.52-3.29 for stroke, 0.56 (95% CI: 0.16-2.00 for myocardial infarction, and 0.92 (95% CI: 0.44-1.92 for stroke/myocardial infarction. CONCLUSIONS: Initiation of amphetamines or atomoxetine was not associated with an elevated risk of serious cardiovascular events. However, some of the confidence intervals do not exclude modest elevated risks, e.g. for sudden death/ventricular arrhythmia.

  18. Protective effects of amphetamine on gastric ulcerations induced by indomethacin in rats

    Institute of Scientific and Technical Information of China (English)

    Vlaicu Sandor; Barbu Cuparencu; Dan L Dumitrascu; Mircea A Birt; Tibor L Krausz

    2006-01-01

    AIM: To study the effects of amphetamine, an indirectacting adrenomimetic compound on the indomethacininduced gastric ulcerations in rats.METHODS: Male Wistar-Bratislava rats were randomly divided into four groups: Group 1 (control), received an ulcerogenic dose of indomethacin (50 μmol/kg) and Groups 2, 3 and 4, treated with amphetamine (10, 25and 50 μmol/kg). The drug was administered simultaneously with indomethacin and once again 4 h later.The animals were sacrificed 8 h after indomethacin treatment. The stomachs were opened and the incidence, the number of lesions and their severity were evaluated. The results were expressed as percentage and as mean ± standard error (mean ± SE).RESULTS: The incidence of ulceration in the control group was 100%. Amphetamine, at doses of 10, 25 and 50 μmol/kg, lowered the incidence to 88.89%, 77.78%and 37.5% respectively. The protection ratio was positive: 24.14%, 55.17% and 80.6% respectively. The total number of ulcerations/rat was 12.44 ± 3.69 in the control group. It decreased to 7.33 ± 1.89, 5.33 ± 2.38 and 2.25 ± 1.97 under the effects of the above-mentioned doses of amphetamine.CONCLUSION: Amphetamine affords a significant dose-dependent protection against the indomethacininduced gastric ulcerations in rats. It is suggested that the adrenergic system is involved in the gastric mucosa protection.

  19. Acute methoxetamine and amphetamine poisoning with fatal outcome: A case report

    Directory of Open Access Journals (Sweden)

    Marek Wiergowski

    2014-08-01

    Full Text Available Methoxetamine (MXE is a psychoactive substance distributed mostly via the Internet and is not liable to legal regulation in Poland. MXE has a toxicity profile similar to that of ketamine but longer-lasting effects. The paper describes a case of acute poisoning that resulted from recreational use of MXE and amphetamine and ended in death. In mid-July 2012, a 31-year old man was admitted to the clinical toxicology unit in Gdańsk because of poisoning with an unknown psychoactive substance. The patient was transported to the emergency department (ED at 5:15 a.m. in a very poor general condition, in a deep coma, with acute respiratory failure, hyperthermia (> 39°C and generalized seizures. Laboratory tests showed marked leukocytosis, signs of massive rhabdomyolysis, hepatic failure and beginning of acute renal failure. Despite intensive therapy, the patient died 4 weeks after the poisoning in the course of multi-organ dysfunction syndrome. Chemical and toxicological studies of serum and urine samples collected on the poisoning day at 1:40 p.m. confirmed that amphetamine and MXE had been taken earlier that day. Concentration of amphetamine in the serum (0.06 μg/ml was within the non-toxic range, while MXE (0.32 μg/ml was within the toxic range of concentrations. Amphetamine was also detected in the patient's hair, which suggested a possibility of its use within the last dozen weeks or so. The serious clinical course of intoxication and co-existence of amphetamine and MXE in the patient's blood and urine suggest the possibility of adverse interactions between them.

  20. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    DEFF Research Database (Denmark)

    Reitzel, Lotte Ask; Holm, Niels Bjerre; Linnet, Kristian;

    2016-01-01

    In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high...... performance liquid chromatography (HPLC) with high-resolution (HR) mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific...... marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol...

  1. The substituted (S)-3-phenylpiperidine (-)-OSU6162 reduces apomorphine- and amphetamine-induced behaviour in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Brandt-Christensen, M; Andersen, M B; Fink-Jensen, A

    2006-01-01

    -amphetamine-induced behaviours in EPS sensitised Cebus apella monkeys. (-)-OSU6162 was administered subcutaneously in doses of 1, 3, 6 and 9 mg/kg alone and in combination with (-)-apomorphine (0.25 mg/kg) or d-amphetamine (0.5 mg/kg). (-)-OSU6162 inhibited (-)-apomorphine-(1-9 mg/kg) as well as d-amphetamine (3-9 mg....../kg)-induced arousal and stereotypy. EPS did not occur when (-)-OSU6162 was administered in combination with (-)-apomorphine or d-amphetamine. However, when (-)-OSU6162 was administered alone, dystonia was observed at high doses (6 and 9 mg/kg) in two out of six monkeys. The present study shows that (-)-OSU6162 can...

  2. Tph2 gene deletion enhances amphetamine-induced hypermotility: effect of 5-HT restoration and role of striatal noradrenaline release.

    Science.gov (United States)

    Carli, Mirjana; Kostoula, Chrysaugi; Sacchetti, Giuseppina; Mainolfi, Pierangela; Anastasia, Alessia; Villani, Claudia; Invernizzi, Roberto William

    2015-11-01

    Variants of tryptophan hydroxylase-2 (Tph2), the gene encoding enzyme responsible for the synthesis of brain serotonin (5-HT), have been associated with neuropsychiatric disorders, substance abuse and addiction. This study assessed the effect of Tph2 gene deletion on motor behavior and found that motor activity induced by 2.5 and 5 mg/kg amphetamine was enhanced in Tph2(-/-) mice. Using the in vivo microdialysis technique we found that the ability of amphetamine to stimulate noradrenaline (NA) release in the striatum was reduced by about 50% in Tph2(-/-) mice while the release of dopamine (DA) was not affected. Tph2 deletion did not affect the release of NA and DA in the prefrontal cortex. The role of endogenous 5-HT in enhancing the effect of amphetamine was confirmed showing that treatment with the 5-HT precursor 5-hydroxytryptophan (10 mg/kg) restored tissue and extracellular levels of brain 5-HT and the effects of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. Treatment with the NA precursor dihydroxyphenylserine (400 mg/kg) was sufficient to restore the effect of amphetamine on striatal NA release and motor activity in Tph2(-/-) mice. These findings indicate that amphetamine-induced hyperactivity is attenuated by endogenous 5-HT through the inhibition of striatal NA release. Tph2(-/-) mice may be a useful preclinical model to assess the role of 5-HT-dependent mechanisms in the action of psychostimulants. Acute sensitivity to the motor effects of amphetamine has been associated to increased risk of psychostimulant abuse. Here, we show that deletion of Tph2, the gene responsible for brain 5-HT synthesis, enhances the motor effect of amphetamine in mice through the inhibition of striatal NA release. This suggests that Tph2(-/-) mice is a useful preclinical model to assess the role of 5-HT-dependent mechanisms in psychostimulants action. Tph2, tryptophan hydroxylase-2.

  3. Surveillance of Diversion and Nonmedical Use of Extended-Release Prescription Amphetamine and Oral Methylphenidate in the United States

    OpenAIRE

    Sembower, Mark A.; Ertischek, Michelle D.; Buchholtz, Chloe; Dasgupta, Nabarun; Schnoll, Sidney H.

    2013-01-01

    This article examines rates of nonmedical use and diversion of extended-release amphetamine and extended-release oral methylphenidate in the United States. Prescription dispensing data were sourced from retail pharmacies. Nonmedical use data were collected from the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) System Drug Diversion Program and Poison Center Program. Drug diversion trends nearly overlapped for extended-release amphetamine and extended-release oral met...

  4. Amphetamine-induced perseverative behavior in a radial arm maze following DSP4 or 6-OHDA pretreatment.

    Science.gov (United States)

    Bruto, V; Beauchamp, C; Zacharko, R M; Anisman, H

    1984-01-01

    Mice permitted to explore an 8-arm radial maze tended to visit those arms least recently entered. Treatment with D-amphetamine engendered a perseverative tendency, wherein mice repeatedly visited two arms of the maze. Administration of the norepinephrine (NE) neurotoxin, N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4), appreciably reduced NE in the hippocampus and cortex, moderately reduced NE in the locus coeruleus, and had only a small effect on hypothalamic NE. The DSP4 treatment resulted in a decrease of locomotor activity among amphetamine-treated mice, coupled with an increase of stereotyped response patterns. Although the NE depletion did not affect the pattern of exploration that mice ordinarily displayed, DSP4 appreciably increased the perseverative tendency provoked by amphetamine. Reduction of dopamine (DA) and NE by intraventricular administration of the catecholamine neurotoxin, 6-hydroxydopamine (6-OHDA), antagonized the effects of amphetamine, such that the frequency of alternation responses was increased and the proportion of perseverative responses was reduced. The effectiveness of the 6-OHDA treatment in antagonizing the amphetamine-induced perseveration was not reduced among mice that were pretreated with desmethylimipramine, which resulted in partial prevention of the NE reduction by 6-OHDA administration. It is suggested that DA neuronal activity contributes to the amphetamine -provoked perseveration , whereas NE stimulation modifies the perseverative tendency by influencing exploration or habituation.

  5. Amphetamine-related mental disorder%精神活性物质所致精神障碍

    Institute of Scientific and Technical Information of China (English)

    陈晗晖; 何燕玲; 诸索宇; 赵敏

    2011-01-01

    @@ 1 病史摘要 患者,男,35岁,因 "反复使用冰毒4年,易激惹2个月,猜疑,耳闻人语伴失眠10 d" 第二次入住上海市精神卫生中心戒毒科.患者于2006年在朋友影响下,因好奇开始吸食冰毒(甲基苯丙胺),当时人很兴奋,不停地说话.最初1 ~2个月才使用一次.2007年使用频率增加,有时隔几天一次,后来几乎每天使用,每次1 ~6条,剂量不等.%A 35-year-old male with a 4-year history of amphetamine abuse was admitted after l0 days of psychotic symptoms.The symptoms resolved after 10 days of treatment with olanzapine and he remained abstinent from amphetamine use for 5 months after discharge, as verified by urine tests at three clinic visits. This case is used to discuss several related issues: the source and classification of amphetamine drugs, the prevalence of amphetamine abuse in youth, the differential diagnosis in drug abusers, clinical problems in managing amphetamine abuse, and the mechanisms underlying the brain changes associated with amphetamine use.

  6. Routine analysis of amphetamine class drugs as their naphthaquinone derivatives in human urine by high-performance liquid chromatography.

    Science.gov (United States)

    Talwar, D; Watson, I D; Stewart, M J

    1999-12-10

    We describe a simple HPLC method which is suitable for the routine confirmation of immunoassay positive amphetamine urine samples. The precolumn derivisation method employing sodium naphthaquinone-4-sulphonate was found to have adequate sensitivity, selectivity and precision for the measurement of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxyethylamphetamine (MDEA) at 500 microg/l cutoff level for confirmatory analysis of amphetamines in urine. The specificity of the method is enhanced by detecting the peaks at two different wavelengths. The ratios of the peak heights measured at the two wavelengths were different for each of the 5 amphetamines analysed. There was no interference from other phenylethylamine analogues that are commonly found in "over the counter" preparations. The HPLC method is compared to a commercial TLC system for detecting amphetamines in urine of drug abusers attending drug rehabilitation programmes. The HPLC confirmatory method described is a viable alternative to GC or to the more complex and costly GC-MS techniques for confirming amphetamine, methamphetamine, MDMA, MDA and MDEA in urine of drug abusers especially when used in a clinical care setting.

  7. Individual differences in timing of peak positive subjective responses to d-amphetamine: Relationship to pharmacokinetics and physiology.

    Science.gov (United States)

    Smith, Christopher T; Weafer, Jessica; Cowan, Ronald L; Kessler, Robert M; Palmer, Abraham A; de Wit, Harriet; Zald, David H

    2016-04-01

    Rate of delivery of psychostimulants has been associated with their positive euphoric effects and potential addiction liability. However, information on individual differences in onset of d-amphetamine's effects remains scarce. We examined individual differences in the time to peak subjective and physiological effects and the pharmacokinetics/pharmacodynamics of oral d-amphetamine. We considered two independent studies that used different dosing regimens where subjects completed the drug effects questionnaire at multiple time points post d-amphetamine. Based on the observation of distinct individual differences in time course of drug effects questionnaire "feel", "high", and "like" ratings (DEQH+L+F) in Study 1, subjects in both studies were categorized as early peak responders (peak within 60 minutes), late peak responders (peak > 60 minutes) or nonresponders; 20-25% of participants were categorized as early peak responders, 50-55% as late peak responders and 20-30% as nonresponders. Physiological (both studies) and plasma d-amphetamine (Study 1) were compared among these groups. Early peak responders exhibited an earlier rise in plasma d-amphetamine levels and more sustained elevation in heart rate compared to late peak responders. The present data illustrate the presence of significant individual differences in the temporal pattern of responses to oral d-amphetamine, which may contribute to heightened abuse potential.

  8. Acute myocardial infarction with multiple coronary thromboses in a young addict of amphetamines and benzodiazepines

    Directory of Open Access Journals (Sweden)

    Mohammed A. Al Shehri

    2016-07-01

    Full Text Available A 35-year-old man of average build and a smoker, with a background of a psychiatric disorder, was brought by his neighbor to the emergency department after an hour of severe chest pain. Upon arrival at the hospital he had cardiac arrest, was resuscitated, and moved to the catheterization laboratory with inferior, posterior, and lateral myocardial infarction. Coronary angiography showed an unusual thrombosis in multiple coronary branches. Toxicology report showed high levels of amphetamines and benzodiazepines in the patient’s original blood sample. The patient was kept under ventilation for 18 days, with difficult recovery due to severe withdrawal manifestations, ventilation acquired pneumonia, and rhabdomyolysis inducing acute renal failure. The patient regained near normal left ventricular function after baseline severe regional and global dysfunction. We postulate a relationship between the use of amphetamines, potentiated by benzodiazepines, and occurrence of acute thrombosis of multiple major coronary arteries.

  9. Dopamine-independent locomotor actions of amphetamines in a novel acute mouse model of Parkinson disease.

    Directory of Open Access Journals (Sweden)

    Tatyana D Sotnikova

    2005-08-01

    Full Text Available Brain dopamine is critically involved in movement control, and its deficiency is the primary cause of motor symptoms in Parkinson disease. Here we report development of an animal model of acute severe dopamine deficiency by using mice lacking the dopamine transporter. In the absence of transporter-mediated recycling mechanisms, dopamine levels become entirely dependent on de novo synthesis. Acute pharmacological inhibition of dopamine synthesis in these mice induces transient elimination of striatal dopamine accompanied by the development of a striking behavioral phenotype manifested as severe akinesia, rigidity, tremor, and ptosis. This phenotype can be reversed by administration of the dopamine precursor, L-DOPA, or by nonselective dopamine agonists. Surprisingly, several amphetamine derivatives were also effective in reversing these behavioral abnormalities in a dopamine-independent manner. Identification of dopamine transporter- and dopamine-independent locomotor actions of amphetamines suggests a novel paradigm in the search for prospective anti-Parkinsonian drugs.

  10. Methylphenidate amplifies the potency and reinforcing effects of amphetamines by increasing dopamine transporter expression.

    Science.gov (United States)

    Calipari, Erin S; Ferris, Mark J; Salahpour, Ali; Caron, Marc G; Jones, Sara R

    2013-01-01

    Methylphenidate (MPH) is commonly diverted for recreational use, but the neurobiological consequences of exposure to MPH at high, abused doses are not well defined. Here we show that MPH self-administration in rats increases dopamine transporter (DAT) levels and enhances the potency of MPH and amphetamine on dopamine responses and drug-seeking behaviours, without altering cocaine effects. Genetic overexpression of the DAT in mice mimics these effects, confirming that MPH self-administration-induced increases in DAT levels are sufficient to induce the changes. Further, this work outlines a basic mechanism by which increases in DAT levels, regardless of how they occur, are capable of increasing the rewarding and reinforcing effects of select psychostimulant drugs, and suggests that individuals with elevated DAT levels, such as ADHD sufferers, may be more susceptible to the addictive effects of amphetamine-like drugs.

  11. Structural elucidation of an uncommon phenylethylamine analogue in urine responsible for discordant amphetamine immunoassay results.

    Science.gov (United States)

    Marson, C; Schneider, S; Meys, F; Wennig, R

    2000-01-01

    The present paper describes investigations following the analysis of a urine specimen containing important amounts of an unknown substance detected by gas chromatography-mass spectrometry (GC-MS) analysis. FPIA analysis was positive (cutoff 0.3 mg/L) and Triage 8 rapid test was negative (cutoff 1 mg/L) for amphetamines. Considering the GC-MS spectrum, two different molecules, for example, N-ethyl-1-(3,4-methylenedioxyphenyl)ethylamine (1) or N-ethyl-4-methoxyamphetamine (2), have been suspected. Synthesis of these two compounds was carried out together with spectral (MS, 1H and 13C NMR, IR, UV) and chromatographic (GC) characterization as well as determination of immunological cross reactivities (FPIA and Triage 8). The unknown compound present in the urine specimen has been finally identified as N-ethyl-4-methoxyamphetamine (2), an uncommon amphetamine analogue.

  12. Adolescent mice are more vulnerable than adults to single injection-induced behavioral sensitization to amphetamine

    OpenAIRE

    Kameda, Sonia Regina; Fukushiro, Daniela Fukue [UNIFESP; Trombin, Thaís Fernanda [UNIFESP; Procopio-Souza, Roberta [UNIFESP; Patti, Camilla de Lima [UNIFESP; Hollais, André Willian [UNIFESP; Calzavara, Mariana Bendlin [UNIFESP; Abílio, Vanessa Costhek [UNIFESP; Ribeiro, Rosana de Alencar [UNIFESP; Tufik, Sergio; D'Almeida, Vânia; Frussa Filho, Roberto [UNIFESP

    2011-01-01

    Drug-induced behavioral sensitization in rodents has enhanced our understanding of why drugs acquire increasing motivational and incentive value. Compared to adults, human adolescents have accelerated dependence courses with shorter times from first exposure to dependence. We compared adolescent and adult mice in their ability to develop behavioral sensitization to amphetamine following a single injection. Adult (90-day-old) and adolescent (45-day-old) male Swiss mice received an acute intrap...

  13. Impulsive choice and environmental enrichment: effects of d-amphetamine and methylphenidate.

    Science.gov (United States)

    Perry, Jennifer L; Stairs, Dustin J; Bardo, Michael T

    2008-11-03

    Individual differences in impulsive choice and rearing in differential environments are factors that predict vulnerability to drug abuse. The present study determined if rearing influences impulsive choice, and if d-amphetamine or methylphenidate alters impulsive choice in differentially reared rats. Male Sprague-Dawley rats were raised from 21 days of age in either an enriched condition (EC) or an isolated condition (IC) and were tested as young adults on an adjusting delay task. In this task, two levers were available and a response on one lever yielded one 45mg food pellet immediately, whereas a response on the other yielded three pellets after an adjusting delay. The delay was initially set at 6s, and it decreased or increased by 1s following responses on the immediate or delayed levers, respectively. A mean adjusted delay (MAD) was calculated upon completion of each daily session, and it served as the quantitative measure of impulsivity. Once MADs stabilized, rats were injected with saline, d-amphetamine (0.5, 1.0, or 2.0mg/kg, s.c.), or methylphenidate (2.5, 5.0, or 10.0mg/kg, s.c.) 15min prior to adjusting delay sessions. EC rats had higher baseline MADs (were less impulsive) than IC rats. Additionally, administration of d-amphetamine, but not methylphenidate, dose-dependently increased impulsive choice (decreased MADs) in EC rats. In IC rats, d-amphetamine and methylphenidate dose-dependently decreased impulsivity (increased MADs). These results indicate that rearing environment influences impulsive choice and moderates the effect of psychostimulants on impulsive choice. Specifically, psychostimulants may decrease environment-dependent impulsive choice in individuals with high levels of impulsivity (e.g., those with ADHD), whereas they may increase impulsive choice in individuals with low levels of impulsivity.

  14. Glucocorticoid receptor gene inactivation in dopamine-innervated areas selectively decreases behavioral responses to amphetamine

    Directory of Open Access Journals (Sweden)

    Sebastien eParnaudeau

    2014-02-01

    Full Text Available The meso-cortico-limbic system, via dopamine release, encodes the rewarding and reinforcing properties of natural rewards. It is also activated in response to abused substances and is believed to support drug-related behaviors. Dysfunctions of this system lead to several psychiatric conditions including feeding disorders and drug addiction. These disorders are also largely influenced by environmental factors and in particular stress exposure. Stressors activate the corticotrope axis ultimately leading to glucocorticoid hormone (GCs release. GCs bind the glucocorticoid receptor (GR a transcription factor ubiquitously expressed including within the meso-cortico-limbic tract. While the GR within dopamine-innervated areas drives cocaine’s behavioral responses, its implication in responses to other psychostimulants such as amphetamine has never been clearly established. Moreover, while extensive work has been made to uncover the role of this receptor in addicted behaviors, its contribution to the rewarding and reinforcing properties of food has yet to be investigated. Using mouse models carrying GR gene inactivation in either dopamine neurons or in dopamine-innervated areas, we found that GR in dopamine responsive neurones is essential to properly build amphetamine-induced conditioned place preference and locomotor sensitization. c-Fos quantification in the nucleus accumbens further confirmed defective neuronal activation following amphetamine injection. These diminished neuronal and behavioral responses to amphetamine may involve alterations in glutamate transmission as suggested by the decreased MK801-elicited hyperlocomotion and by the hyporeactivity to glutamate of a subpopulation of medium spiny neurons. In contrast, GR inactivation did not affect rewarding and reinforcing properties of food suggesting that responding for natural reward under basal conditions is preserved in these mice.

  15. Rapid GC-MS confirmation of amphetamines in urine by extractive acylation.

    Science.gov (United States)

    Marais, Adriaan A S; Laurens, Johannes B

    2009-01-10

    Amphetamine and related derivatives are widely abused central- and psychostimulants. Detection of certain derivatives, such as methcathinone, by commonly available immunoassay screening techniques is insufficient. Multi-analyte confirmations for amphetamine type stimulants are therefore required, but traditional gas chromatography-mass spectrometry methods necessitate lengthy analytical procedures with prolonged sample turn-around times. A validated rapid GC-MS assay for urinary confirmation of amphetamine, methamphetamine, methcathinone, ephedrine, norephedrine, methylenedioxyamphetamine, methylenedioxymethamphetamine, methylenedioxyethylamphetamine and N-methyl-1-(3,4 methylenedioxyphenyl)-2-butanamine is reported. The method entailed in situ derivatization of urine specimens by extractive acylation with pentafluoropropionic anhydride, followed by rapid chromatography on a microbore capillary column. Analytes were separated in less than 3 min and quantified simultaneously by selected-ion monitoring using stable isotope substituted internal standards. The total instrument cycle-time was 6 min per sample. The limits of detection were between 1.5 ng/mL and 6.25 ng/mL for the various analytes. Intermediate precision and accuracy were in the range of 6.3-13.8% and 90.5-107.3% for the respective analytes at the lower limit of quantitation, and between 5.8-12.6% and 95.4-103.1% for the high control. Long-term storage of methcathinone positive specimens at -20 degrees C proved insufficient stability of this analyte. The proposed assay is precise and accurate for confirmation of amphetamine and derivatives in urine. The complementary approach of extractive-derivatization and fast GC-MS analysis is especially applicable in routine clinical settings where reduced sample turn-around times are required. Further investigation of cathinone as a possible metabolite of methcathinone is warranted, based on results from analyzed authentic urine samples.

  16. Keto amphetamine toxicity-focus on the redox reactivity of the cathinone designer drug mephedrone.

    Science.gov (United States)

    den Hollander, Bjørnar; Sundström, Mira; Pelander, Anna; Ojanperä, Ilkka; Mervaala, Eero; Korpi, Esa Risto; Kankuri, Esko

    2014-09-01

    The β-keto amphetamine (cathinone, β-KA) designer drugs such as mephedrone (4-methylmethcathinone, 4-MMC) show a large degree of structural similarity to amphetamines like methamphetamine (METH). However, little is currently known about whether these substances also share the potential neurotoxic properties of their non-keto amphetamine counterparts, or what mechanisms could be involved. Here, we evaluate the cytotoxicity of β-KAs in SH-SY5Y cells using lactate dehydrogenase (LDH) assays, assess the redox potential of a range of β-KAs and non-keto amphetamines using the sensitive redox indicator 2-(4-Iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-1), and explore the effect of 4-MMC on the formation of protein adducts using ultra-high performance liquid chromatography/high-resolution time-of-flight mass spectrometry (UHPLC-HR-TOFMS) and on the mitochondrial respiratory chain using high-resolution respirometry. We show that treatment with β-KAs increases LDH release. Further, we demonstrate that even under physiological pH, β-KAs are effective and selective-as compared with their non-keto analogues-reductants in the presence of electron acceptors. Increased pH (range 7.6-8.0) greatly enhanced the reactivity up to sixfold. We found no evidence of protein adduct formation, suggesting the reactivity is due to direct electron transfer by the β-KAs. Finally, we show that 4-MMC and METH produce dissimilar effects on the respiratory chain. Our results indicate that β-KAs such as 4-MMC possess cytotoxic properties in vitro. Furthermore, in the presence of an electron-accepting redox partner, the ketone moiety of β-KAs is vital for pH-dependent redox reactivity. Further work is needed to establish the importance of β-KA redox properties and its potential toxicological importance in vivo.

  17. Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

    Science.gov (United States)

    Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

    2011-12-01

    Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

  18. Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

    Science.gov (United States)

    O’Daly, Owen G.; Joyce, Daniel; Tracy, Derek K.; Azim, Adnan; Stephan, Klaas E.; Murray, Robin M.; Shergill, Sukhwinder S.

    2014-01-01

    Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders. PMID:24717936

  19. Amphetamine sensitization alters reward processing in the human striatum and amygdala.

    Directory of Open Access Journals (Sweden)

    Owen G O'Daly

    Full Text Available Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.

  20. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine

    Directory of Open Access Journals (Sweden)

    Michael Pennick

    2010-06-01

    Full Text Available Michael PennickBiosciences Department, Shire Pharmaceutical Development Ltd, Basingstoke, UKAbstract: These studies investigated the absorption and metabolic conversion of lisdexamfetamine dimesylate (LDX, a prodrug stimulant that requires conversion to d-amphetamine for activity. Oral absorption of LDX was assessed in rat portal and jugular blood, and perfusion of LDX into isolated intestinal segments of anesthetized rats was used to assess regional absorption. Carrier-mediated transport of LDX was investigated in Caco-2 cells and Chinese hamster ovary (CHO cells expressing human peptide transporter-1 (PEPT1. LDX metabolism was studied in rat and human tissue homogenates and human blood fractions. LDX was approximately10-fold higher in portal blood versus systemic blood. LDX and d-amphetamine were detected in blood following perfusion of the rat small intestine but not the colon. Transport of LDX in Caco-2 cells had permeability apparently similar to cephalexin and was reduced with concurrent PEPT1 inhibitor. Affinity for PEPT1 was also demonstrated in PEPT1-transfected CHO cells. LDX metabolism occurred primarily in whole blood (rat and human, only with red blood cells. Slow hydrolysis in liver and kidney homogenates was probably due to residual blood. The carrier-mediated absorption of intact LDX, likely by the high-capacity PEPT1 transporter, and subsequent metabolism to d-amphetamine in a high-capacity system in blood (ie, red blood cells may contribute to the consistent, reproducible pharmacokinetic profile of LDX.Keywords: lisdexamfetamine dimesylate, LDX, prodrug, ADHD, absorption, Vyvanse

  1. Khat use and appetite: An overview and comparison of amphetamine, khat and cathinone

    Science.gov (United States)

    Lemieux, Andrine M.; Li, Bingshuo; al’Absi, Mustafa

    2014-01-01

    Ethnopharmacological relevance To understand the role of khat (Catha edulis) use on the aberrations in appetite and weight which are common comorbidities for khat and other amphetamine users. Materials and methods We provide a comprehensive overview and conceptual summary of the historical cultural use of khat as a natural stimulant and describe the similarities and differences between cathinone (the main psychoactive constituent of khat) and amphetamine highlighting the limited literature on the neurophysiology of appetite and subsequent weight effects of khat. Results Animal and some human studies indicate that khat produces appetite suppression, although little is known about mechanisms of this effect. Both direct and indirect effects of khat stem from multiple factors including behavioral, chemical and neurophysiological effects on appetite and metabolism. Classic and newly identified appetite hormones have not been explored sufficiently in the study of appetite and khat use. Unique methodological challenges and opportunities are encountered when examining effects of khat and cathinone including khat-specific medical comorbidities, unique route of administration, differential patterns of behavioral effects relative to amphetamines and the nascent state of our understanding of the neurobiology of this drug. Conclusion A considerable amount of work remains in the study of the appetite effects of khat chewing and outline a program of research that could inform our understanding of this natural amphetamine’s appetite effects and help prepare health care workers for the unique health effects of this drug. PMID:25435289

  2. DPP IV inhibitor blocks mescaline-induced scratching and amphetamine-induced hyperactivity in mice.

    Science.gov (United States)

    Lautar, Susan L; Rojas, Camilo; Slusher, Barbara S; Wozniak, Krystyna M; Wu, Ying; Thomas, Ajit G; Waldon, Daniel; Li, William; Ferraris, Dana; Belyakov, Sergei

    2005-06-28

    Dipeptidyl peptidase IV (DPP IV) is a ubiquitous membrane-bound enzyme that cleaves the two N-terminal amino acids from peptides with a proline or alanine residue in the second position from the amino end. Potential substrates for DPP IV include several neuropeptides, suggesting a role for DPP IV in neurological processes. We have developed a potent DPP IV inhibitor (IC50 = 30 nM), 1-(2-amino-3-methyl-butyryl)-azetidine-2-carbonitrile (AMAC), which has shown efficacy in two established models of psychosis: mescaline-induced scratching and amphetamine-induced hyperactivity. In the mescaline-induced scratching model, AMAC treatment before mescaline administration reduced the number of scratching paroxysms by 68% (P < 0.01). The compound showed a dose-dependent effect, inhibiting significantly at 6, 20 and 60 mg/kg (37%, 39% and 68%, respectively). In the amphetamine-induced hyperactivity model, 50 and 60 mg/kg AMAC, given before injection of amphetamine, significantly reduced hyper-locomotion by 65% and 76%, respectively. Additionally, AMAC showed no significant activity in binding assays for 20 receptors thought to be involved in the pathology of schizophrenia, including dopamine, serotonin and glutamate. A structurally similar analog, 1-(2-dimethylamino-3-methyl-butyryl)-azetidine-2-carbonitrile (DAMAC), that does not inhibit DPP IV, was inactive in both models. Taken together, these data suggest that the antipsychotic effects of AMAC are the result of DPP IV inhibition.

  3. Predictors of Hazardous Alcohol Consumption Among Young Adult Amphetamine-Type Stimulant Users

    Directory of Open Access Journals (Sweden)

    Ellen M. Leslie

    2016-02-01

    Full Text Available Background: Very high levels of alcohol consumption have been observed in young adult amphetamine-type stimulant (i.e., ecstasy and methamphetamine users. The reasons for this association are poorly understood. Objective: To examine predictors of hazardous alcohol consumption in a sample of young adult amphetamine-type stimulant users after 30 months of follow-up, controlling for potential confounders. Method: Analysis of longitudinal data from a population-derived sample of Australian young adult amphetamine-type stimulant users (n = 292. A prediction model of alcohol use at 30 months was developed using generalized linear latent and mixed modeling (GLLAMM. Results: Concurrently using ecstasy (Adjusted Odds Ratio [AOR] = 2.67, 95% Confidence Interval [CI] = [1.41, 5.07], frequently attending nightclubs (AOR = 2.53, 95% CI = [1.04, 6.16], high baseline alcohol use patterns (AOR = 2.06, 95% CI = [1.32, 3.20], and being male (AOR = 3.60, 95% CI = [1.48, 8.78] were associated with an increased likelihood of hazardous alcohol use at 30 months. Conclusion: Concurrent, but not baseline, ecstasy use was associated with hazardous alcohol use, suggesting that combined use of these substances may have an instrumental role in terms of the social functions of drug use (e.g., increasing capacity to drink. Integration of educational interventions concerning alcohol and stimulants is warranted.

  4. Performance enhancing, non-prescription use of Ritalin: a comparison with amphetamines and cocaine.

    Science.gov (United States)

    Svetlov, Stanislay I; Kobeissy, Firas H; Gold, Mark S

    2007-01-01

    Ritalin, known under chemical name methylphenidate (MPH), is a psychostimulant prescribed to treat attention-deficit/hyperactivity disorder (ADHD) and other conditions. Psychotropic effects and pharmacological pathways evoked by MPH are similar, but not identical to those produced by amphetamines and cocaine. Although not completely understood in detail, MPH psychostimulation is mediated by the increase of central dopamine (DA) and possibly norepinephrine (NE) and serotonin (ST) due to decrease of their re-uptake via binding to and inhibition of DA, NE, and ST transporters. Despite similarity in psychopharmacological effects, the rewarding/ reinforcing ability of MPH appears to be significantly lower than amphetamines and especially cocaine. MPH and similar medications have been widely used on College campuses and by students preparing for exams. Nicknamed 'steroids for SATs,' MPH and related medications are purchased without prescription and their use may even be encouraged by parents and tutors. However, while widely and safely used and administered for over forty years, Ritalin generated significant controversy including MPH abuse and addiction, and adverse reactions. It is now clear that treatment of ADD/ADHD with psychostimulants prevents drug abuse and addictions. Use by those without any medical or psychiatric diagnosis is increasing. In this mini-review, we discuss psychopharmacological and behavioral aspects, and outline neurochemical mechanisms that may provoke Ritalin abuse, addiction and adverse effects compared to amphetamines and cocaine.

  5. Determination of amphetamines in biological samples using electro enhanced solid-phase microextraction-gas chromatography.

    Science.gov (United States)

    Zeng, Jingbin; Chen, Jingjing; Li, Min; Subhan, Fazle; Chong, Fayun; Wen, Chongying; Yu, Jianfeng; Cui, Bingwen; Chen, Xi

    2015-09-01

    In this work, an ordered mesoporous carbon (OMC)/Nafion coated fiber for solid-phase microextraction (SPME) was prepared and used as the working electrode for electro-enhanced SPME (EE-SPME) of amphetamines. The EE-SPME strategy is primarily based on the electro-migration and complementary charge interaction between fiber coating and ionic compounds. Compared with traditional SPME, EE-SPME exhibited excellent extraction efficiency for amphetamine (AP) and methamphetamine (MA) with an enhancement factor of 7.8 and 12.1, respectively. The present strategy exhibited good linearity for the determination of AP and MA in urine samples in the range of 10-1000ngmL(-1) and 20-1000ngmL(-1), respectively. The detection limits were found to be 1.2ngmL(-1) for AP and 4.8ngmL(-1) for MA. The relative standard deviations were calculated to be 6.2% and 8.5% for AP and MA, respectively. Moreover, the practical application of the proposed method was demonstrated by analyzing the amphetamines in urine and serum samples with satisfactory results.

  6. Neurotoxicity of drugs of abuse--the case of methylenedioxyamphetamines (MDMA, ecstasy), and amphetamines.

    Science.gov (United States)

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2009-01-01

    Ecstasy (MDMA, 3,4-methylendioxymethamphetamine) and the stimulants methamphetamine (METH, speed) and amphetamine are popular drugs among young people, particularly in the dance scene. When given in high doses both MDMA and the stimulant amphetamines are clearly neurotoxic in laboratory animals. MDMA causes selective and persistent lesions of central serotonergic nerve terminals, whereas amphetamines damage both the serotonergic and dopaminergic systems. In recent years, the question of ecstasy-induced neurotoxicity and possible functional sequelae has been addressed in several studies in drug users. Despite large methodological problems, the bulk of evidence suggests residual alterations of serotonergic transmission in MDMA users, although at least partial recovery may occur after long-term abstinence. However, functional sequelae may persist even after longer periods of abstinence. To date, the most consistent findings associate subtle cognitive impairments with ecstasy use, particularly with memory. In contrast, studies on possible long-term neurotoxic effects of stimulant use have been relatively scarce. Preliminary evidence suggests that alterations of the dopaminergic system may persist even after years of abstinence from METH, and may be associated with deficits in motor and cognitive performance. In this paper, we will review the literature focusing on human studies.

  7. Application of solvent microextraction to the analysis of amphetamines and phencyclidine in urine.

    Science.gov (United States)

    Casari, C; Andrews, A R

    2001-09-01

    A fast and simple method to detect some commonly abused illicit drugs, amphetamine, methamphetamine, 3,4-methylendioxy-amphetamine (MDA), 3,4-methylendioxy-methamphetamine (MDMA), 3,4-methylendioxy-N-ethylamphetamine (MDEA) and phencyclidine (PCP) in urine using solvent microextraction (SME) combined with gas chromatography (GC) analysis has been developed. The extraction is conducted by suspending a 2 microl drop of chloroform in a 2 ml urine sample. Following 8 min of extraction, the organic solvent is withdrawn into the syringe and injected into a GC with a pulsed discharge helium ionization detector (PDHID). The effects of different extraction solvents and times, pH and sample preparation were studied. The optimized method was capable of detecting drugs in urine at concentrations below Substance Abuse and Mental Health Services Administration (SAMHSA) established cut-off values for preliminary testing. Good linearity and reproducibility of extraction were obtained. The limits of detection were 0.5 microg/ml for amphetamine, 0.1 microg/ml for methamphetamine and MDA, 0.05 microg/ml for MDMA, 0.025 microg/ml for MDEA and 0.015 microg/ml for PCP. Relative standard deviation (R.S.D.) values ranged between 5 and 20% for the studied drugs.

  8. Different reactivities of amphetamines with N-methyl-bis(trifluoroacetamide) in heated gas chromatographic injectors.

    Science.gov (United States)

    Hidvégi, E; Hideg, Zs; Somogyi, G P

    2008-03-01

    A fast gas chromatographic mass spectrometric method has been developed earlier for the determination of amphetamine derivatives in human serum and urine. For derivatization, N-methyl-bis(trifluoroacetamide) (MBTFA) was used. Derivatization was performed using an on-line mode, since 1 microl of MBTFA and 1 microl sample extract, dissolved in toluene were injected simultaneously. In this study, the reactivity of the several amphetamine type analytes with MBTFA was investigated. MBTFA used for flash derivatization was applied undiluted on the one hand and diluted 4--4096-fold with acetonitrile on the other hand. Studying several amphetamines in the test sample spiked at the same concentrations we found that they could be divided into 3 groups based on relative target ion peak areas as a function of MBTFA dilution. Group 1, containing only primary amines showed an early increase of the relative peak areas if we increased MBTFA concentration, where group 2 (mainly N-methyl secondary amines) showed that relative peak areas started to increase intensively at higher MBTFA concentrations. Finally, MDEA as an N-ethyl secondary amine, representing group 3, showed significant increase if only slightly diluted MBTFA was used as a flash reagent. This phenomenon can be explained mainly with the less and less reactivity of amine groups in the case of groups 2 and 3, compared to group 1. These findings could help to optimise analytical methods involving flash derivatization processes.

  9. Midkine Is a Novel Regulator of Amphetamine-Induced Striatal Gliosis and Cognitive Impairment: Evidence for a Stimulus-Dependent Regulation of Neuroinflammation by Midkine

    Science.gov (United States)

    Vicente-Rodríguez, Marta; Fernández-Calle, Rosalía; Gramage, Esther; Pérez-García, Carmen; Ramos, María P.

    2016-01-01

    Midkine (MK) is a cytokine that modulates amphetamine-induced striatal astrogliosis, suggesting a possible role of MK in neuroinflammation induced by amphetamine. To test this hypothesis, we studied astrogliosis and microglial response induced by amphetamine (10 mg/kg i.p. four times, every 2 h) in different brain areas of MK−/− mice and wild type (WT) mice. We found that amphetamine-induced microgliosis and astrocytosis are enhanced in the striatum of MK−/− mice in a region-specific manner. Surprisingly, LPS-induced astrogliosis in the striatum was blocked in MK−/− mice. Since striatal neuroinflammation induced by amphetamine-type stimulants correlates with the cognitive deficits induced by these drugs, we also tested the long-term effects of periadolescent amphetamine treatment (3 mg/kg i.p. daily for 10 days) in a memory task in MK−/− and WT mice. Significant deficits in the Y-maze test were only observed in amphetamine-pretreated MK−/− mice. The data demonstrate for the first time that MK is a novel modulator of neuroinflammation depending on the inflammatory stimulus and the brain area considered. The data indicate that MK limits amphetamine-induced striatal neuroinflammation. In addition, our data demonstrate that periadolescent amphetamine treatment in mice results in transient disruption of learning and memory processes in absence of endogenous MK. PMID:28044069

  10. Monoamine transporter and receptor interaction profiles of novel psychoactive substances: para-halogenated amphetamines and pyrovalerone cathinones.

    Science.gov (United States)

    Rickli, Anna; Hoener, Marius C; Liechti, Matthias E

    2015-03-01

    The pharmacology of novel psychoactive substances is mostly unknown. We evaluated the transporter and receptor interaction profiles of a series of para-(4)-substituted amphetamines and pyrovalerone cathinones. We tested the potency of these compounds to inhibit the norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporters (NET, DAT, and SERT, respectively) using human embryonic kidney 293 cells that express the respective human transporters. We also tested the substance-induced efflux of NE, DA, and 5-HT from monoamine-loaded cells, binding affinities to monoamine receptors, and 5-HT2B receptor activation. Para-(4)-substituted amphetamines, including 4-methylmethcathinone (mephedrone), 4-ethylmethcathinone, 4-fluoroamphetamine, 4-fluoromethamphetamine, 4-fluoromethcatinone (flephedrone), and 4-bromomethcathinone, were relatively more serotonergic (lower DAT:SERT ratio) compared with their analogs amphetamine, methamphetamine, and methcathinone. The 4-methyl, 4-ethyl, and 4-bromo groups resulted in enhanced serotonergic properties compared with the 4-fluoro group. The para-substituted amphetamines released NE and DA. 4-Fluoramphetamine, 4-flouromethamphetamine, 4-methylmethcathinone, and 4-ethylmethcathinone also released 5-HT similarly to 3,4-methylenedioxymethamphetamine. The pyrovalerone cathinones 3,4-methylenedioxypyrovalerone, pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxy-α-pyrrolidinopropiophenone, and 3,4-methylenedioxy-α-pyrrolidinobutiophenone potently inhibited the NET and DAT but not the SERT. Naphyrone was the only pyrovalerone that also inhibited the SERT. The pyrovalerone cathinones did not release monoamines. Most of the para-substituted amphetamines exhibited affinity for the 5-HT2A receptor but no relevant activation of the 5-HT2B receptor. All the cathinones exhibited reduced trace amine-associated receptor 1 binding compared with the non-β-keto-amphetamines. In conclusion, para-substituted amphetamines exhibited

  11. PKC phosphorylates residues in the N-terminal of the DA transporter to regulate amphetamine-induced DA efflux.

    Science.gov (United States)

    Wang, Qiang; Bubula, Nancy; Brown, Jason; Wang, Yunliang; Kondev, Veronika; Vezina, Paul

    2016-05-27

    The DA transporter (DAT), a phosphoprotein, controls extracellular dopamine (DA) levels in the central nervous system through transport or reverse transport (efflux). Multiple lines of evidence support the claim that PKC significantly contributes to amphetamine-induced DA efflux. Other signaling pathways, involving CaMKII and ERK, have also been shown to regulate DAT mediated efflux. Here we assessed the contribution of putative PKC residues (S4, S7, S13) in the N-terminal of the DAT to amphetamine-induced DA efflux by transfecting DATs containing different serine to alanine (S-A) point mutations into DA pre-loaded HEK-293 cells and incubating these cells in amphetamine (2μM). The effects of a S-A mutation at the non-PKC residue S12 and a threonine to alanine (T-A) mutation at the ERK T53 residue were also assessed for comparison. WT-DATs were used as controls. In an initial experiment, we confirmed that inhibiting PKC with Go6976 (130nM) significantly reduced amphetamine-induced DA efflux. In subsequent experiments, cells transfected with the S4A, S12A, S13A, T53A and S4,7,13A mutants showed a reduction in amphetamine-induced DA efflux similar to that observed with Go6976. Interestingly, cells transfected with the S7A mutant, identified by some as a PKC-PKA residue, showed unperturbed WT-DAT levels of amphetamine-induced DA efflux. These results indicate that phosphorylation by PKC of select residues in the DAT N-terminal can regulate amphetamine-induced efflux. PKC can act either independently or in concert with other kinases such as ERK to produce this effect.

  12. Reinforcing, subject-rated, performance and physiological effects of methylphenidate and d-amphetamine in stimulant abusing humans.

    Science.gov (United States)

    Stoops, William W; Glaser, Paul E A; Fillmore, Mark T; Rush, Craig R

    2004-12-01

    Methylphenidate has potential for abuse because it produces behavioural effects similar to those observed with other abused stimulants, such as d-amphetamine and cocaine. The aim of this study was to further characterize the abuse potential of oral methylphenidate relative to oral d-amphetamine. Ten drug-abusing volunteers were recruited to participate in this study, which consisted of seven dose conditions: methylphenidate (16, 32 and 48 mg), d-amphetamine (8, 16 and 24 mg) and placebo. The reinforcing effects of these drugs were assessed during a self-administration session (preceded by a sampling session for each condition) with a modified progressive-ratio procedure. Subject-rated, performance and physiological effects were assessed concurrently during both the sampling and self-administration sessions. The intermediate dose of methylphenidate and d-amphetamine increased responding significantly above placebo levels. Both methylphenidate and d-amphetamine produced dose-dependent increases in stimulant-like subject ratings (e.g. Active, Alert, or Energetic and High), but the effects of these drugs were not isomorphic. These findings are consistent with epidemiological data and previous findings from laboratory studies that suggest methylphenidate has at least some abuse potential.

  13. Estimation of gamma-hydroxybutyrate (GHB) co-consumption in serum samples of drivers positive for amphetamine or ecstasy.

    Science.gov (United States)

    Lott, S; Musshoff, F; Madea, B

    2012-09-10

    There is no toxicological analysis of gamma-hydroxybutyrate (GHB) applied routinely in cases of driving under influence (DUI); therefore the extent of consumption of this drug might be underestimated. Its consumption is described as occurring often concurrently with amphetamine or ecstasy. This study examines 196 serum samples which were collected by police during road side testing for GHB. The samples subject to this study have already been found to be positive for amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and/or 3,4-methylenedioxyethamphetamine (MDEA). Analysis has been performed by LC/MS/MS in the multiple reaction monitoring (MRM) mode. Due to its polarity, chromatographic separation of GHB was achieved by a HILIC column. To differentiate endogenous and exogenous levels of GHB, a cut-off concentration of 4μg/ml was applied. Of the 196 samples, two have been found to be positive for GHB. Of these samples, one sample was also positive for amphetamine and one for MDMA. Whilst other amphetamine derivates were not detected in these samples, both samples were found to be positive for cannabinoids. These results suggest that co-consumption of GHB with amphetamine or ecstasy is relatively low (1%) for the collective of this study.

  14. Accelerated habit formation following amphetamine exposure is reversed by D1, but enhanced by D2, receptor antagonists

    Directory of Open Access Journals (Sweden)

    Andrew John Dudley Nelson

    2013-05-01

    Full Text Available Repeated exposure to the psychostimulant amphetamine has been shown to disrupt goal-directed instrumental actions and promote the early and abnormal development of goal-insensitive habitual responding (Nelson and Killcross, 2006. To investigate the neuropharmacological specificity of this effect as well as restore goal-directed responding in animals with pre-training amphetamine exposure, animals were treated with the non-selective dopamine antagonist α-flupenthixol, the selective D1 antagonist SCH 23390 or the selective D2 antagonist eticlopride, prior to instrumental training (3 sessions. Subsequently, the reinforcer was paired with LiCL-induced gastric-malaise and animals were given a test of goal-sensitivity both in extinction and reacquisition. The effect of these dopaminergic antagonists on the sensitivity of lever press performance to outcome devaluation was assessed in animals with pre-training exposure to amphetamine (Experiments 1a-1c or in non-sensitized animals (Experiment 2. Both α-flupenthixol and SCH23390 reversed accelerated habit formation following amphetamine sensitization. However, eticlopride appeared to enhance this effect and render instrumental performance compulsive as these animals were unable to inhibit responding both in extinction and reacquisition, even though a consumption test confirmed they had acquired an aversion to the reinforcer. These findings demonstrate that amphetamine induced-disruption of goal-directed behaviour is mediated by activity at distinct dopamine receptor subtypes and may represent a putative model of the neurochemical processes involved in the loss of voluntary control over behaviour.

  15. The role of 5-HT(2A) receptor antagonism in amphetamine-induced inhibition of A10 dopamine neurons in vitro

    NARCIS (Netherlands)

    Olijslagers, J.E.; Perlstein, B.; Werkman, T.R.; Mc.Creary, A.C.; Siarey, R.; Kruse, C.G.; Wadman, W.J.

    2005-01-01

    The role of the 5-HT(2A) receptor in modulating amphetamine-induced inhibition of dopamine neuronal firing in A9 and A10 was investigated in rat midbrain slices. The antipsychotic drugs olanzapine and clozapine more potently reversed the amphetamine-induced inhibition in A10 neurons compared to A9 n

  16. Lack of delayed effects of amphetamine, methoxamine, and prazosin (adrenergic drugs) on behavioral outcome after lateral fluid percussion brain injury in the rat.

    Science.gov (United States)

    Dose, J M; Dhillon, H S; Maki, A; Kraemer, P J; Prasad, R M

    1997-05-01

    This study examined the delayed effects of the administration of d-amphetamine, methoxamine (an alpha1-adrenergic receptor agonist), and prazosin (an alpha1-adrenergic receptor antagonist) on the behavioral outcome of lateral fluid-percussion (FP) brain injury. Rats trained to perform a beam-walking task were subjected to brain injury of moderate severity (2.1 to 2.2 atm). Twenty-four hours after injury, rats were treated with amphetamine, methoxamine, or prazosin at two or three different dose levels. Amphetamine-treated animals displayed no significant improvement in beam-walking ability either during or after drug intoxication (from days 3 to 5 after brain injury). Similarly, neither methoxamine nor prazosin significantly affected beam-walking ability during or after drug intoxication. Neither amphetamine treatment at three different doses nor treatment with methoxamine or prazosin at two different doses affected the spatial learning disabilities of brain-injured animals. These results suggest that (1) unlike amphetamine administration after sensorimotor cortex (SMC) ablation or contusion brain injury models, amphetamine administration at 24 h after concussive FP brain injury does not improve beam-walking performance; (2) unlike amphetamine administration 10 min after concussive FP brain injury amphetamine administration 24 h after injury does not improve cognitive function; and (3) unlike prazosin administration after SMC ablation brain injury, prazosin administration 24 h after concussive FP brain injury does not effect beam-walking performance.

  17. Adulterants and diluents in heroin, amphetamine, and cocaine found on the illicit drug market in Aarhus, Denmark

    DEFF Research Database (Denmark)

    Andreasen, Mette Findal; Lindholst, Christian; Kaa, Elisabet

    2009-01-01

    The aim of the present study was to investigate the composition of heroin, amphetamine, and cocaine seized in the police district of Aarhus, the second largest city in Denmark, during a 2-year period. The purity of the active substance was measured together with the frequency and purity of adulte......The aim of the present study was to investigate the composition of heroin, amphetamine, and cocaine seized in the police district of Aarhus, the second largest city in Denmark, during a 2-year period. The purity of the active substance was measured together with the frequency and purity...... of adulterants and diluents present in the drugs. Results are compared with a similar study conducted ten years earlier. The concentrations of the active substances in illicit heroin, amphetamine, and cocaine samples have decreased significantly over a 10-year period. This finding shows that the "cutting...

  18. Surface-activated chemical ionization ion trap mass spectrometry in the analysis of amphetamines in diluted urine samples.

    Science.gov (United States)

    Cristoni, Simone; Bernardi, Luigi Rossi; Gerthoux, Piermario; Gonella, Elisabetta; Mocarelli, Paolo

    2004-01-01

    A new ionization method, named surface-activated chemical ionization (SACI), was employed for the analysis of five amphetamines (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDE), amphetamine and methamphetamine) by ion trap mass spectrometry. The results so obtained have been compared with those achieved by using atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) using the same instrument, clearly showing that SACI is the most sensitive of the three. The limit of detection and linearity range for SACI were compared with those obtained using APCI and ESI, showing that the new SACI approach provides the best results for both criteria. SACI was used to analyze MDA, MDMA MDE, amphetamine and methamphetamine in four urine samples, and the quantitation results are compared with those achieved using ESI.

  19. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Stiefel, Gary; Besag, Frank M C

    2010-10-01

    Attention-deficit hyperactivity disorder (ADHD) is a very common condition in children and often extends into the adult years. Drugs such as methylphenidate, amphetamines and atomoxetine are frequently prescribed as part of management. The use of these drugs has been increasing and significant clinical benefit is achieved but safety has been questioned. In this review, the cardiovascular safety of these drugs is examined with regard to effects on blood pressure (BP), heart rate (HR), ECG parameters and the risk of sudden death. Methylphenidate appears to cause minor increases in BP and HR. There are no strong data to suggest that methylphenidate increases the corrected QT interval (QTc). Amphetamines appear to cause minor increases in HR and BP over the long term. There is growing evidence to suggest that amphetamines do not cause statistically or clinically significant increases in QTc. Sudden death remains an extremely rare event and there is no clear evidence to attribute this to methylphenidate. Some data even suggest that the risk of sudden death in treated children may be less common than in the background population. Limited data suggest that atomoxetine may increase BP and HR in the short term; in the long term it appears to increase BP. The effects of atomoxetine on QTc remain uncertain. Use of this drug does not appear to be associated with sudden death. Because the current evidence is based on research that has not been specifically designed to investigate the cardiovascular effects of these drugs it is difficult to draw firm conclusions, and further work is required specifically to address these questions.

  20. The neurotoxicity of hallucinogenic amphetamines in primary cultures of hippocampal neurons.

    Science.gov (United States)

    Capela, João Paulo; da Costa Araújo, Silvana; Costa, Vera Marisa; Ruscher, Karsten; Fernandes, Eduarda; Bastos, Maria de Lourdes; Dirnagl, Ulrich; Meisel, Andreas; Carvalho, Félix

    2013-01-01

    3,4-Methylenedioxymethamphetamine (MDMA or "Ecstasy") and 2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) are hallucinogenic amphetamines with addictive properties. The hippocampus is involved in learning and memory and seems particularly vulnerable to amphetamine's neurotoxicity. We evaluated the neurotoxicity of DOI and MDMA in primary neuronal cultures of hippocampus obtained from Wistar rat embryos (E-17 to E-19). Mature neurons after 10 days in culture were exposed for 24 or 48 h either to MDMA (100-800 μM) or DOI (10-100 μM). Both the lactate dehydrogenase (LDH) release and the tetrazolium-based (MTT) assays revealed a concentration- and time-dependent neuronal death and mitochondrial dysfunction after exposure to both drugs. Both drugs promoted a significant increase in caspase-8 and caspase-3 activities. At concentrations that produced similar levels of neuronal death, DOI promoted a higher increase in the activity of both caspases than MDMA. In the mitochondrial fraction of neurons exposed 24h to DOI or MDMA, we found a significant increase in the 67 kDa band of apoptosis inducing factor (AIF) by Western blot. Moreover, 24h exposure to DOI promoted an increase in cytochrome c in the cytoplasmatic fraction of neurons. Pre-treatment with an antibody raised against the 5-HT(2A)-receptor (an irreversible antagonist) greatly attenuated neuronal death promoted by 48 h exposure to DOI or MDMA. In conclusion, hallucinogenic amphetamines promoted programmed neuronal death involving both the mitochondria machinery and the extrinsic cell death key regulators. Death was dependent, at least in part, on the stimulation of the 5-HT(2A)-receptors.

  1. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters.

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F; Schmid, Rainer; Sitte, Harald H; Kudlacek, Oliver

    2014-07-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect "fades out" the levamisole/aminorex effect "kicks in".

  2. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters☆

    Science.gov (United States)

    Hofmaier, Tina; Luf, Anton; Seddik, Amir; Stockner, Thomas; Holy, Marion; Freissmuth, Michael; Ecker, Gerhard F.; Schmid, Rainer; Sitte, Harald H.; Kudlacek, Oliver

    2014-01-01

    Psychostimulants such as amphetamine and cocaine are illicitly used drugs that act on neurotransmitter transporters for dopamine, serotonin or norepinephrine. These drugs can by themselves already cause severe neurotoxicity. However, an additional health threat arises from adulterant substances which are added to the illicit compound without declaration. One of the most frequently added adulterants in street drugs sold as cocaine is the anthelmintic drug levamisole. We tested the effects of levamisole on neurotransmitter transporters heterologously expressed in HEK293 cells. Levamisole was 100 and 300-fold less potent than cocaine in blocking norepinephrine and dopamine uptake, and had only very low affinity for the serotonin transporter. In addition, levamisole did not trigger any appreciable substrate efflux. Because levamisole and cocaine are frequently co-administered, we searched for possible allosteric effects; at 30 μM, a concentration at which levamisole displayed already mild effects on norepinephrine transport it did not enhance the inhibitory action of cocaine. Levamisole is metabolized to aminorex, a formerly marketed anorectic drug, which is classified as an amphetamine-like substance. We examined the uptake-inhibitory and efflux-eliciting properties of aminorex and found it to exert strong effects on all three neurotransmitter transporters in a manner similar to amphetamine. We therefore conclude that while the adulterant levamisole itself has only moderate effects on neurotransmitter transporters, its metabolite aminorex may exert distinct psychostimulant effects by itself. Given that the half-time of levamisole and aminorex exceeds that of cocaine, it may be safe to conclude that after the cocaine effect “fades out” the levamisole/aminorex effect “kicks in”. PMID:24296074

  3. Simultaneous quantification of cocaine, amphetamines, opiates and cannabinoids in vitreous humor.

    Science.gov (United States)

    Peres, Mariana Dadalto; Pelição, Fabrício Souza; Caleffi, Bruno; De Martinis, Bruno Spinosa

    2014-01-01

    A GC-MS method for simultaneous analysis of cocaine (COC), amphetamines (AMPs), opiates, cannabinoids and their metabolites in vitreous humor (VH) was developed and fully validated. VH samples were extracted using solid phase extraction and injected into the GC-MS, using a selected ion monitoring mode. Linearity ranged from 10 to 1000 ng/mL; the exception was anhydroecgonine methyl ester (AEME), for which linearity ranged from 10 to 750 ng/mL. Inter-assay imprecision lay from 1.2 to 10.0%, intra-assay imprecision was opiates and their metabolites.

  4. -Amphetamine and Antipsychotic Drug Effects on Latent Inhibition in Mice Lacking Dopamine D2 Receptors

    OpenAIRE

    Bay-Richter, C.; O'Callaghan, M J; N Mathur; O'Tuathaigh, C.M.P.; Heery, D M; Fone, K C F; Waddington, J. L.; Moran, P.M.

    2013-01-01

    Drugs that induce psychosis, such as -amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd 2 −/−), we first investigated whether D2 is required for AMP disruption ...

  5. [AWMF-guideline: cocaine-, amphetamine-, ecstasy- and hallucinogen-related disorders].

    Science.gov (United States)

    Thomasius, R; Gouzoulis-Mayfrank, E; Karus, C; Wiedenmann, H; Hermle, L; Sack, P M; Zeichner, D; Küstner, U; Schindler, A; Krüger, A; Uhlmann, S; Petersen, K U; Zapletalova, P; Wartberg, L; Schütz, C G; Schulte-Markwort, M; Obrocki, J; Heinz, A; Schmoldt, A

    2004-12-01

    Actually, guidelines for treatment of substance-related disorders were written under the overall control of the DG-Sucht e. V. and the DGPPN e. V. This appears within the framework of the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaft (AWMF). The leading objective of these guidelines is the description of the current scientifically proven and evidence-based medicine in addiction to derive recommendations to therapy. In this context, the guideline for treatment of cocaine-, amphetamine-, ecstasy-, and halluzinogen-related disorders is introduced.

  6. Delusional Parasitosis in a Female Treated with Mixed Amphetamine Salts: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Martha Buscarino

    2012-01-01

    Full Text Available Objectives. To explore factors underlying the onset of delusional parasitosis; a condition in which an individual has a fixed, false belief that he/she is infested with insects. Case Description. MJ is a 57-year-old female who presents with symptoms of fatigue and AD/HD. Upon treatment with extended release mixed amphetamine salts, the patient displayed symptoms of delusional parasitosis. After eventual discontinuation of this medication, her delusions resolved. Comments. In order to maintain confidentiality, all identifying information was removed. To this end, please note that MJ is a fictitious name.

  7. Amphetamine concentrations in human urine following single-dose administration of the calcium antagonist prenylamine-studies using fluorescence polarization immunoassay (FPIA) and GC-MS.

    Science.gov (United States)

    Kraemer, Thomas; Roditis, Susanne K; Peters, Frank T; Maurer, Hans H

    2003-03-01

    Prenylamine (R,S-N-(3,3-diphenylpropyl-methyl-2-phenethylamine), a World Health Organization class V calcium antagonist, is known to be metabolized to amphetamine. In this study, amphetamine concentrations after a single-dose administration of prenylamine were determined to check if they reached values that could be of analytical and/or pharmacological importance in clinical and forensic toxicology. Enantiomeric composition of amphetamine was also studied. Five volunteers received a single 120-mg oral dose of prenylamine. Urine samples were analyzed using the Abbott TDx immunoassay Amphetamine/Methamphetamine II and using our routine systematic toxicological analysis (STA) gas chromatography-mass spectrometry (GC-MS) procedure. For quantitation purposes, GC-MS was used in the selected-ion monitoring (SIM) mode (ions m/z 118, 122, 240, 244) after solid-phase extraction (Isolute Confirm HCX) and derivatization (heptafluorobutyric anhydride). Amphetamine-d5 was used as internal standard (IS). Chiral separation of the heptafluorobutyrated amphetamine enantiomers was achieved using an Astec Chiraldex G-PN column. The TDx results showed a great variability for the different volunteers. A urine sample of one volunteer showed results as high as 3200 ng/mL, whereas the urine samples of another volunteer never gave results greater than the TDx detection limit (100 ng/mL). Using the STA procedure, the presence of amphetamine could be confirmed in all urine samples with TDx results greater than the cutoff value (300 ng/mL). Using the GC-MS SIM method, amphetamine concentrations up to 1280 ng/mL were determined. Chiral analysis revealed that both enantiomers of amphetamine were present in the samples with a surplus of the S(+)-enantiomer in the early phase of excretion. Forensic implications are discussed.

  8. High fat diet augments amphetamine sensitization in mice: Role of feeding pattern, obesity, and dopamine terminal changes.

    Science.gov (United States)

    Fordahl, Steve C; Locke, Jason L; Jones, Sara R

    2016-10-01

    High fat (HF) diet-induced obesity has been shown to augment behavioral responses to psychostimulants that target the dopamine system. The purpose of this study was to characterize dopamine terminal changes induced by a HF diet that correspond with enhanced locomotor sensitization to amphetamine. C57BL/6J mice had limited (2hr 3 d/week) or extended (24 h 7 d/week) access to a HF diet or standard chow for six weeks. Mice were then repeatedly exposed to amphetamine (AMPH), and their locomotor responses to an amphetamine challenge were measured. Fast scan cyclic voltammetry was used to identify changes in dopamine terminal function after AMPH exposure. Exposure to a HF diet reduced dopamine uptake and increased locomotor responses to acute, high-dose AMPH administration compared to chow fed mice. Microdialysis showed elevated extracellular dopamine in the nucleus accumbens (NAc) coincided with enhanced locomotion after acute AMPH in HF-fed mice. All mice exhibited locomotor sensitization to amphetamine, but both extended and limited access to a HF diet augmented this response. Neither HF-fed group showed the robust amphetamine sensitization-induced increases in dopamine release, reuptake, and amphetamine potency observed in chow fed animals. However, the potency of amphetamine as an uptake inhibitor was significantly elevated after sensitization in mice with extended (but not limited) access to HF. Conversely, after amphetamine sensitization, mice with limited (but not extended) access to HF displayed reduced autoreceptor sensitivity to the D2/D3 agonist quinpirole. Additionally, we observed reduced membrane dopamine transporter (DAT) levels after HF, and a shift in DAT localization to the cytosol was detected with limited access to HF. This study showed that different patterns of HF exposure produced distinct dopamine terminal adaptations to repeated AMPH, which differed from chow fed mice, and enhanced sensitization to AMPH. Locomotor sensitization in chow fed

  9. Calmodulin Kinase II Interacts with the Dopamine Transporter C Terminus to Regulate Amphetamine-Induced Reverse Transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  10. Calmodulin kinase II interacts with the dopamine transporter C terminus to regulate amphetamine-induced reverse transport

    DEFF Research Database (Denmark)

    Fog, Jacob U; Khoshbouei, Habibeh; Holy, Marion

    2006-01-01

    Efflux of dopamine through the dopamine transporter (DAT) is critical for the psychostimulatory properties of amphetamines, but the underlying mechanism is unclear. Here we show that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) plays a key role in this efflux. CaMKIIalpha bound to the d...... in response to the CaMKII inhibitor KN93. Our data suggest that CaMKIIalpha binding to the DAT C terminus facilitates phosphorylation of the DAT N terminus and mediates amphetamine-induced dopamine efflux....

  11. Heroin and amphetamine users display opposite relationships between trait and neurobehavioral dimensions of impulsivity.

    Science.gov (United States)

    Vassileva, Jasmin; Paxton, Jessica; Moeller, F Gerard; Wilson, Michael J; Bozgunov, Kiril; Martin, Eileen M; Gonzalez, Raul; Vasilev, Georgi

    2014-03-01

    The multidimensional construct of impulsivity is implicated in all phases of the addiction cycle. Substance dependent individuals (SDIs) demonstrate elevated impulsivity on both trait and laboratory tests of neurobehavioral impulsivity; however our understanding of the relationship between these different aspects of impulsivity in users of different classes of drugs remains rudimentary. The goal of this study was to assess for commonalities and differences in the relationships between trait and neurobehavioral impulsivity in heroin and amphetamine addicts. Participants included 58 amphetamine dependent (ADIs) and 74 heroin dependent individuals (HDIs) in protracted abstinence. We conducted Principal Component Analyses (PCA) on two self-report trait and six neurobehavioral measures of impulsivity, which resulted in two trait impulsivity (action, planning) and four neurobehavioral impulsivity composites (discriminability, response inhibition efficiency, decision-making efficiency, quality of decision-making). Multiple regression analyses were used to determine whether neurobehavioral impulsivity is predicted by trait impulsivity and drug type. The analyses revealed a significant interaction between drug type and trait action impulsivity on response inhibition efficiency, which showed opposite relationships for ADIs and HDIs. Specifically, increased trait action impulsivity was associated with worse response inhibition efficiency in ADIs, but with better efficiency in HDIs. These results challenge the unitary account of drug addiction and contribute to a growing body of literature that reveals important behavioral, cognitive, and neurobiological differences between users of different classes of drugs.

  12. The role of the GABA system in amphetamine-type stimulant use disorders

    Directory of Open Access Journals (Sweden)

    Dongliang eJiao

    2015-05-01

    Full Text Available Abuse of amphetamine-type stimulants (ATS has become a global public health problem. ATS causes severe neurotoxicity, which could lead to addiction and could induce psychotic disorders or cognitive dysfunctions. However, until now, there has been a lack of effective medicines for treating ATS-related problems. Findings from recent studies indicate that in addition to the traditional dopamine-ergic system, the GABA (gamma-aminobutyric acid-ergic system plays an important role in ATS abuse. However the exact mechanisms of the GABA-ergic system in amphetamine-type stimulant use disorders are not fully understood. This review discusses the role of the GABA-ergic system in ATS use disorders, including ATS induced psychotic disorders and cognitive dysfunctions. We conclude that the GABA-ergic system are importantly involved in the development of ATS use disorders through multiple pathways, and that therapies or medicines that target specific members of the GABA-ergic system may be novel effective interventions for the treatment of ATS use disorders.

  13. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine.

    Science.gov (United States)

    Contreras, Marco; Riveros, María E; Quispe, Maricel; Sánchez, Cristián; Perdomo, Guayec; Torrealba, Fernando; Valdés, José L

    2016-01-01

    The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.

  14. New Psychoactive Substances: Chemistry, Pharmacology, Metabolism, and Detectability of Amphetamine Derivatives With Modified Ring Systems.

    Science.gov (United States)

    Welter-Luedeke, Jessica; Maurer, Hans H

    2016-02-01

    In recent years, new amphetamine derivatives with modified ring systems were sold and consumed as new drugs of abuse. They belong together with other new drugs of abuse classes to the so-called new psychoactive substances (NPS). The chemistry, pharmacology, toxicology, metabolism, and toxicokinetics are shortly discussed of camfetamine, 3 methylphenyl-amphetamines (2-MA, 3-MA, and 4-MA), 2-methiopropamine (2-MPA), and 5-(2-aminopropyl)benzofuran (5-APB), 6-(2-aminopropyl)benzofuran (6-APB, so-called "benzofury") and their N-methyl derivatives 5-MAPB and 6-MAPB. Only a rough assessment of the pharmacology and toxicology NPS can be performed in most cases using published data of analogs, trip reports, and described clinical cases. Accordingly, they all act more or less as central nervous stimulants mainly by increasing the concentration of the neurotransmitters noradrenaline, dopamine, and serotonin (5-HT) by inducing their release and reuptake inhibition. Thus, the acute toxicity is associated with the sympathomimetic effects, such as mydriasis, hyperthermia, hypertension, tachycardia, insomnia, and anxiety. With the exception of 5- and 6-APB, these NPS were extensively metabolized by N-demethylation and/or aromatic hydroxylation catalyzed by various cytochrome P450 isoenzymes followed by partial glucuronidation and/or sulfation. For urinalysis, the unchanged drugs and/or the nor-metabolites are the main targets.

  15. Effects of indorenate on food intake: a comparison with fenfluramine and amphetamine.

    Science.gov (United States)

    Velázquez Martínez, D N; Valencia Flores, M; López Cabrera, M; Villarreal, J E

    1995-01-01

    Indorenate (TR3369, 5-methoxytryptamine b-methylcarboxylate HCl) is a 5-HT1-like receptor agonist with hypotensive activity. Here, we describe that indorenate also decreases food intake (ED50 26.1 mg/kg) without an appreciable effect in water intake (the estimated ED50 for water was 589.8 mg/kg). The anorectic activity of indorenate was compared to the effects of amphetamine and other serotonin agonists; the effect of indorenate was smaller than those of the other compounds; however, the effect of indorenate was specific to food, whereas all the other drugs also produced significant decrements in water intake. The serotonin antagonists cinanserin, cyproheptadine, methergoline and methysergide effectively prevented the decrease in food intake produced by indorenate and fenfluramine. Haloperidol, a dopaminergic antagonist, was ineffective in preventing the effect of indorenate although it prevented the anorectic effect of amphetamine. The present results suggest the participation of serotoninergic, but not dopaminergic mechanisms, in the decrease in food intake produced by indorenate.

  16. New chlorinated amphetamine-type-stimulants disinfection-by-products formed during drinking water treatment.

    Science.gov (United States)

    Huerta-Fontela, Maria; Pineda, Oriol; Ventura, Francesc; Galceran, Maria Teresa

    2012-06-15

    Previous studies have demonstrated high removal rates of amphetamine-type-stimulants (ATSs) through conventional drinking water treatments; however the behaviour of these compounds through disinfection steps and their transformation into disinfection-by-products (DBPs) is still unknown. In this work, for the first time, the reactivity of some ATSs such as amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA) with chlorine has been investigated under simulated and real drinking water treatment conditions in order to evaluate their ability to give rise to transformation products. Two new DBPs from these illicit drugs have been found. A common chlorinated-by-product (3-chlorobenzo)-1,3-dioxole, was identified for both MDA and MDEA while for MDMA, 3-chlorocatechol was found. The presence of these DBPs in water samples collected through drinking water treatment was studied in order to evaluate their formation under real conditions. Both compounds were generated through treatment from raw river water samples containing ATSs at concentration levels ranging from 1 to 15 ng/L for MDA and from 2.3 to 78 ng/L for MDMA. One of them, (3-chlorobenzo)-1,3-dioxole, found after the first chlorination step, was eliminated after ozone and GAC treatment while the MDMA DBP mainly generated after the postchlorination step, showed to be recalcitrant and it was found in final treated waters at concentrations ranging from 0.5 to 5.8 ng/L.

  17. Co-occurring amphetamine use and associated medical and psychiatric comorbidity among opioid-dependent adults: results from the Clinical Trials Network

    Directory of Open Access Journals (Sweden)

    Blazer DG

    2011-07-01

    Full Text Available Daniel J Pilowsky1, Li-Tzy Wu2, Bruce Burchett2, Dan G Blazer2, George E Woody3, Walter Ling41Departments of Epidemiology and Psychiatry, Columbia University, and the New York State Psychiatric Institute, New York City, NY; 2Department of Psychiatry and Behavioral Sciences, School of Medicine, Duke University Medical Center, Durham, NC; 3Department of Psychiatry, School of Medicine, University of Pennsylvania and Treatment Research Institute, Philadelphia, PA; 4David Geffen School of Medicine, NPI/Integrated Substance Abuse Programs, University of California, Los Angeles, CA, USABackground: In response to the rising rate of treatment admissions related to illicit use of amphetamines (eg, methamphetamine, we examined the prevalence of amphetamine use among treatment-seeking, opioid-dependent adults, explored whether amphetamine users were as likely as nonamphetamine users to enroll in opioid-dependence treatment trials, and determined whether amphetamine users manifested greater levels of medical and psychiatric comorbidity than nonusers.Methods: The sample included 1257 opioid-dependent adults screened for participation in threemultisite studies of the National Drug Abuse Treatment Clinical Trials Network (CTN001-003, which studied the effectiveness of buprenorphine for opioid detoxification under varying treatment conditions. Patients were recruited from 23 addiction treatment programs across the US. Medical and psychiatric comorbidity were examined by past-month amphetamine use (current vs former and route of administration. Five mutually exclusive groups were examined, ie, nonusers, current amphetamine injectors, current amphetamine noninjectors, former amphetamine injectors, and former amphetamine noninjectors.Results: Of the sample (n = 1257, 22.3% had a history of regular amphetamine use. Of the 280 amphetamine users, 30.3% reported injection as their primary route. Amphetamine users were more likely than nonusers to be white and use more

  18. Determination of amphetamine, methamphetamine, MDA and MDMA in human hair by GC-EI-MS after derivatization with perfluorooctanoyl chloride

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe; Jornil, Jakob

    2009-01-01

    The aim of this study was to develop a quantitative gas chromatography mass spectrometry (GC-MS) method to determine the classical amphetamines and their methylenedioxylated derivatives in human hair. The procedure involved liquid-liquid extraction of hydrolysed hair spiked with deuterated intern...

  19. A case story, involving the use of maltitol, a sugar alcohol, as a cutting agent in amphetamine and cocaine powders

    Directory of Open Access Journals (Sweden)

    Reitzel Lotte Ask

    2016-06-01

    Full Text Available In a criminal case involving cutting and resale of amphetamine and cocaine in the Copenhagen area of Denmark, maltitol was used as a cutting agent. The analysis of maltitol in seizures of pure diluents as well as in amphetamine and cocaine powders was carried out using reversed-phase high performance liquid chromatography (HPLC with high-resolution (HR mass spectrometric detection. Maltitol was identified in four out of nine amphetamine samples and in five out of six cocaine samples from the case in question. The use of maltitol as a cutting agent was considered by the police as a specific marker of the particular criminal group under investigation. To support or reject this hypothesis, cocaine and amphetamine samples from a four month period after the involved persons had been arrested were evaluated, also as part of the police investigation. None of these samples contained maltitol. The work described covers the part of the case involving the department of forensic chemistry, and not the whole police investigation, but everything was done within the frames given by the police. To the best of our knowledge, this is the first report of a disaccharide polyol being used as a cutting agent for illicit drugs.

  20. [Amphetamine use by truck drivers on highways of Sao Paulo State: a risk for the occurrence of traffic accidents?].

    Science.gov (United States)

    Takitane, Juliana; de Oliveira, Lucio Garcia; Endo, Ligia Góes; de Oliveira, Keziah Cristina Barbosa Gruber; Muñoz, Daniel Romero; Yonamine, Mauricio; Leyton, Vilma

    2013-05-01

    The use of amphetamines in Brazil is common among truck drivers, which may be an important factor in the occurrence of traffic accidents. This article seeks to estimate the prevalence of amphetamine use among truck drivers. Drivers (N = 134) were stopped on two different highways in Sao Paulo state and they were asked to answer a questionnaire and provide a urine sample for toxicological analysis. All data were analyzed on Stata 8.0. All participants were males with low levels of schooling, whose mean age was 40.8 years. The presence of amphetamines was detected in 10.8% of all urine samples collected, being commonly justified in order to make truck drivers able to maintain their state of awareness. Amphetamine use was detected among truck drivers on Sao Paulo highways. The problem is that when the stimulant effects wear off, sleepiness due to sleep deprivation reduces concentration and good driver performance, making drivers vulnerable to traffic accidents and the related effects.

  1. Comparative Effects of Methylphenidate and Mixed Salts Amphetamine on Height and Weight in Children with Attention-Deficit/Hyperactivity Disorder

    Science.gov (United States)

    Pliszka, Steven R.; Matthews, Thomas L.; Braslow, Kenneth J.; Watson, Melissa A.

    2006-01-01

    Objective: To determine whether methylphenidate (MPH) and mixed salts amphetamine (MSA) have different effects on growth in children with attention-deficit/hyperactivity disorder. Method: Patients treated for at least 1 year with MPH or MSA were identified. A linear regression was performed to determine the effect of stimulant type, patient…

  2. Effectiveness and safety of amphetamine for ADHD in population between 6 and 19 years: a systematic review

    Directory of Open Access Journals (Sweden)

    José Calleja

    2012-09-01

    Full Text Available Introduction: Attention deficit hyperactivity disorder (ADHD drug treatment is based on psychostimulants, and methylphenidate is still the most widely used one. Other psychostimulants used include amphetamines, hence the importance of knowing both its effectiveness and safety. Purpose: To identify, synthesize and evaluate the best available evidence on the effectiveness and safety of amphetamine in ADHD in the 6-19 year-old population. Methods: A systematic review of studies that evaluated the effectiveness of interventions comparing amphetamine to methylphenidate was conducted. The outcomes measured were educational performance, psychosocial functioning, quality of life and adverse effects. The following databases were searched up to February 2012 in English and Spanish: PubMed/MEDLINE, LILACS, Cochrane, DARE and National Guideline Clearinghouse. The articles that met inclusion criteria were assessed by two researchers independently. Results: Of the 114 studies found initially, four were included, among which a systematic review, a primary article and two clinical guidelines. Conclusions: The evidence on amphetamine for ADHD treatment recommends its use as an alternative to MPH. Further good-quality studies are needed.

  3. Effects of heavy particle irradiation and diet on amphetamine- and lithium chloride-induced taste avoidance learning in rats

    Science.gov (United States)

    Rabin, Bernard M.; Shukitt-Hale, Barbara; Szprengiel, Aleksandra; Joseph, James A.

    2002-01-01

    Rats were maintained on diets containing either 2% blueberry or strawberry extract or a control diet for 8 weeks prior to being exposed to 1.5 Gy of 56Fe particles in the Alternating Gradient Synchrotron at Brookhaven National Laboratory. Three days following irradiation, the rats were tested for the effects of irradiation on the acquisition of an amphetamine- or lithium chloride-induced (LiCl) conditioned taste avoidance (CTA). The rats maintained on the control diet failed to show the acquisition of a CTA following injection of amphetamine. In contrast, the rats maintained on antioxidant diets (strawberry or blueberry extract) continued to show the development of an amphetamine-induced CTA following exposure to 56Fe particles. Neither irradiation nor diet had an effect on the acquisition of a LiCl-induced CTA. The results are interpreted as indicating that oxidative stress following exposure to 56Fe particles may be responsible for the disruption of the dopamine-mediated amphetamine-induced CTA in rats fed control diets; and that a reduction in oxidative stress produced by the antioxidant diets functions to reinstate the dopamine-mediated CTA. The failure of either irradiation or diet to influence LiCl-induced responding suggests that oxidative stress may not be involved in CTA learning following injection of LiCl.

  4. Application of solid-phase microextraction combined with derivatization to the determination of amphetamines by liquid chromatography.

    Science.gov (United States)

    Cháfer-Pericás, C; Campíns-Falcó, P; Herráez-Hernández, R

    2004-10-15

    This work evaluates the utility of solid-phase microextraction (SPME) in the analysis of amphetamines by liquid chromatography (LC) after chemical derivatization of the analytes. Two approaches have been tested and compared, SPME followed by on-fiber derivatization of the extracted amphetamines, and solution derivatization followed by SPME of the derivatives formed. Both methods have been applied to measure amphetamine (AP), methamphetamine (MA), and 3,4-methylenedioxymethamphetamine (MDMA), using the fluorogenic reagent 9-fluorenylmethyl chloroformate (FMOC) and carbowax-templated resin (CW-TR)-coated fibers. Data on the application of the proposed methods for the analysis of different kind of samples are presented. When analyzing aqueous solutions of the analytes, both approaches gave similar analytical performance, but the sensitivity attainable with the solution derivatization/SPME method was better. The efficiencies observed when processing spiked urine samples by the SPME/on-fiber derivatization approach were very low. This was because the extraction of matrix components into the fiber coating prevented the extraction of the reagent. In contrast, the efficiencies obtained for spiked urine samples by the solution derivatization/SPME approach were similar to those obtained for aqueous samples. Therefore, the later method would be the method of choice for the quantification of amphetamines in urine.

  5. Cardiovascular effects of 0.5 milligrams per kilogram oral d-amphetamine and possible attenuation by haloperidol.

    Science.gov (United States)

    Angrist, B; Sanfilipo, M; Wolkin, A

    2001-01-01

    In a series of earlier studies, an oral dose of 0.5 mg/kg d-amphetamine was administered to 81 patients with schizophrenia and eight normal control subjects. Seven more subjects with schizophrenia received placebo. Blood pressure and pulse rate were monitored before and 3 hours after drug administration. Blood pressure increased in both amphetamine groups, whereas placebo had no effect. However, pulse rate did not change in the schizophrenic group and only increased after 3 hours in normal control subjects as blood pressure began to decrease. Significant negative correlations between systolic blood pressure and pulse rate occurred at 2 and 3 hours, suggesting that the early cardiovascular response to amphetamine is an increase in blood pressure that recruits reflex control of heart rate. Eighteen of these subjects had hypertensive responses. Six subjects received 5 mg haloperidol intramuscularly, and 12 others had their blood pressure monitored until normalization. Haloperidol led to a more rapid decline of some but not all indices of blood pressure, suggesting that amphetamine-induced hypertension may have a dopaminergic component.

  6. Glycogen synthase kinase-3β inhibition in the medial prefrontal cortex mediates paradoxical amphetamine action in a mouse model of ADHD

    Directory of Open Access Journals (Sweden)

    Yi-Chun eYen

    2015-03-01

    Full Text Available Psychostimulants show therapeutic efficacy in the treatment of attention-deficit hyperactivity disorder (ADHD. It is generally assumed that they ameliorate ADHD symptoms via interfering with monoaminergic signaling. We combined behavioral pharmacology, neurochemistry and molecular analyses to identify mechanisms underlying the paradoxical calming effect of amphetamine in low trait anxiety behavior (LAB mice, a novel multigenetic animal model of ADHD. Amphetamine (1 mg/kg and methylphenidate (10 mg/kg elicited similar dopamine and norepinephrine release in the medial prefrontal cortex (mPFC and in the striatum of LAB mice. In contrast, amphetamine decreased, while methylphenidate increased locomotor activity. This argues against changes in dopamine and/or norepinephrine release as mediators of amphetamine paradoxical effects. Instead, the calming activity of amphetamine corresponded to the inhibition of glycogen synthase kinase3β (GSK3β activity, specifically in the mPFC. Accordingly, not only systemic administration of the GSK3β inhibitor TDZD-8 (20 mg/kg, but also local microinjections of TDZD-8 and amphetamine into the mPFC, but not into the striatum, decreased locomotor activity in LAB mice. Amphetamine effects seem to depend on NMDA receptor signaling, since pre- or co-treatment with MK-801 (0.3 mg/kg abolished the effects of amphetamine (1 mg/kg on the locomotion and on the phosphorylation of GSK3β at the level of the mPFC. Taken together, the paradoxical calming effect of amphetamine in hyperactive LAB mice concurs with a decreased GSK3β activity in the mPFC. This effect appears to be independent of dopamine or norepinephrine release, but contingent on NMDA receptor signaling.

  7. An insight into the hepatocellular death induced by amphetamines, individually and in combination: the involvement of necrosis and apoptosis.

    Science.gov (United States)

    Dias da Silva, Diana; Carmo, Helena; Lynch, Adam; Silva, Elisabete

    2013-12-01

    The liver is a vulnerable target for amphetamine toxicity, but the mechanisms involved in the drug's hepatotoxicity remain poorly understood. The purpose of the current research was to characterize the mode of death elicited by four amphetamines and to evaluate whether their combination triggered similar mechanisms in immortalized human HepG2 cells. The obtained data revealed a time- and temperature-dependent mortality of HepG2 cells exposed to 3,4-methylenedioxymethamphetamine (MDMA, ecstasy; 1.3 mM), methamphetamine (3 mM), 4-methylthioamphetamine (0.5 mM) and D-amphetamine (1.7 mM), alone or combined (1.6 mM mixture). At physiological temperature (37 °C), 24-h exposures caused HepG2 death preferentially by apoptosis, while a rise to 40.5 °C favoured necrosis. ATP levels remained unaltered when the drugs where tested at normothermia, but incubation at 40.5 °C provoked marked ATP depletion for all treatments. Further investigations on the apoptotic mechanisms triggered by the drugs (alone or combined) showed a decline in BCL-2 and BCL- XL mRNA levels, with concurrent upregulation of BAX, BIM, PUMA and BID genes. Elevation of Bax, cleaved Bid, Puma, Bak and Bim protein levels was also seen. To the best of our knowledge, Puma, Bim and Bak have never been linked with the toxicity induced by amphetamines. Time-dependent caspase-3/-7 activation, but not mitochondrial membrane potential (∆ψm) disruption, also mediated amphetamine-induced apoptosis. The cell dismantling was confirmed by poly(ADP-ribose)polymerase proteolysis. Overall, for all evaluated parameters, no relevant differences were detected between individual amphetamines and the mixture (all tested at equieffective cytotoxic concentrations), suggesting that the mode of action of the amphetamines in combination does not deviate from the mode of action of the drugs individually, when eliciting HepG2 cell death.

  8. GBR12909 attenuates amphetamine-induced striatal dopamine release as measured by [(11)C]raclopride continuous infusion PET scans.

    Science.gov (United States)

    Villemagne, V L; Wong, D F; Yokoi, F; Stephane, M; Rice, K C; Matecka, D; Clough, D J; Dannals, R F; Rothman, R B

    1999-09-15

    Major neurochemical effects of methamphetamine include release of dopamine (DA), serotonin (5-HT), and norepinephrine (NE) via a carrier-mediated exchange mechanism. Preclinical research supports the hypothesis that elevations of mesolimbic DA mediate the addictive and reinforcing effects of methamphetamine and amphetamine. This hypothesis has not been adequately tested in humans. Previous in vivo rodent microdialysis demonstrated that the high affinity DA uptake inhibitor, GBR12909, attenuates cocaine- and amphetamine-induced increases in mesolimbic DA. The present study determined the ability of GBR12909 to attenuate amphetamine-induced increases in striatal DA as measured by [(11)C]raclopride continuous infusion positron emission tomography (PET) scans in two Papio anubis baboons. [(11)C]Raclopride was given in a continuous infusion paradigm resulting in a flat volume of distribution vs. time for up to 45 min postinjection. At that time, a 1.5 mg/kg amphetamine i.v. bolus was administered which caused a significant (30.3%) reduction in the volume of distribution (V(3)"). The percent reduction in the volume of distribution and, hence, a measure of the intrasynaptic DA release ranged between 22-41%. GBR12909 (1 mg/kg, slow i.v. infusion) was administered 90 min before the administration of the radiotracer. The comparison of the volume of distribution before and after administration of GBR12909 showed that GBR12909 inhibited amphetamine-induced DA release by 74%. These experiments suggest that GBR12909 is an important prototypical medication to test the hypothesis that stimulant-induced euphoria is mediated by DA and, if the DA hypothesis is correct, a potential treatment agent for cocaine and methamphetamine abuse. Furthermore, this quantitative approach demonstrates a way of testing various treatment medications, including other forms of GBR12909 such as a decanoate derivative.

  9. Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a DCC-dependent manner.

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    Reynolds, Lauren M; Makowski, Carolina S; Yogendran, Sandra V; Kiessling, Silke; Cermakian, Nicolas; Flores, Cecilia

    2015-03-13

    Initiation of drug use during adolescence is a strong predictor of both the incidence and severity of addiction throughout the lifetime. Intriguingly, adolescence is a period of dynamic refinement in the organization of neuronal connectivity, in particular medial prefrontal cortex (mPFC) dopamine circuitry. The guidance cue receptor, DCC (deleted in colorectal cancer), is highly expressed by dopamine neurons and orchestrates their innervation to the mPFC during adolescence. Furthermore, we have shown that amphetamine in adolescence regulates DCC expression in dopamine neurons. Drugs in adolescence may therefore induce their enduring behavioral effects via DCC-mediated disruption in mPFC dopamine development. In this study, we investigated the impact of repeated exposure to amphetamine during adolescence on both the development of mPFC dopamine connectivity and on salience attribution to drug context in adulthood. We compare these effects to those induced by adult exposure to an identical amphetamine regimen. Finally, we determine whether DCC signaling within dopamine neurons is necessary for these events. Exposure to amphetamine in adolescence, but not in adulthood, leads to an increase in the span of dopamine innervation to the mPFC, but a reduction of presynaptic sites present on these axons. Amphetamine treatment in adolescence, but not in adulthood, also produces an increase in salience attribution to a previously drug-paired context in adulthood. Remarkably, DCC signaling within dopamine neurons is required for both of these effects. Drugs of abuse in adolescence may therefore induce their detrimental behavioral consequences by disrupting mesocortical dopamine development through alterations in the DCC signaling cascade.

  10. Time-dependent effects of post-trial amphetamine treatment in rats: evidence for enhanced storage of representational memory.

    Science.gov (United States)

    Strupp, B J; Bunsey, M; Levitsky, D; Kesler, M

    1991-07-01

    Two studies were conducted to test the ability of post-trial amphetamine treatment to improve later recall in a nonaversively motivated task. These studies utilized 8- and 12-arm radial mazes, respectively, with an 11-h retention interval imposed after the rat traversed half the arms of the maze (termed, the to-be-remembered-event, or TBRE). In Experiment 1, the rats were injected with amphetamine (0, .25, and .50 mg/kg) immediately after the TBRE. Because the drug treatment improved retention, a time dependency study was conducted in which the drug (0 and .33 mg/kg) was administered 0, 3, and 6 h after the TBRE. The finding that amphetamine injection at 0, but not 3, h post-trial improved later recall indicates that the benefit derived from the former treatment is not due to proactive influences at the time of the retention test. Drug treatment 6 h post-trial produced a borderline improvement of recall; possible mechanisms are discussed. Two conclusions can be drawn from these results: (1) amphetamine administration can improve recall under conditions in which this effect cannot be attributed to alterations in information processing during either the learning or the retention sessions, indicating that the drug modulates memory storage processes; and (2) amphetamine treatment can improve working memory, thus excluding an alternative interpretation for the previous reports of impaired short-term memory in animals, all of which entailed assessments of working memory. The possibility remains, however, that the impairment seen in these tasks reflects the requirement for erasure of information from previous trials within each daily session, rather than the duration of the retention interval.

  11. Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine.

    Science.gov (United States)

    Martin-Iverson, M T; Todd, K G; Altar, C A

    1994-03-01

    To investigate behavioral and neurochemical effects of neurotrophic factors in vivo, rats received continuous 14 d infusions of either brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or vehicle unilaterally into the substantia nigra. BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period. BDNF elevated daytime and nocturnal locomotion compared with infusions of vehicle or NT-3. At 2 weeks, a systemic injection of amphetamine (1.5 mg/kg, s.c.) increased the frequencies and durations of rotations contraversive to the side of BDNF and NT-3 infusions. Both factors attenuated amphetamine-induced locomotion without affecting amphetamine-induced stereotyped behaviors such as sniffing, head movements, and snout contact with cage surfaces. Only BDNF induced backward walking, and this response was augmented by amphetamine. BDNF, but not NT-3, increased dopamine turnover in the striatum ipsilateral to the infusion relative to the contralateral striatum. Both trophic factors decreased dopamine turnover in the infused substantia nigra relative to the contralateral hemisphere and increased 5-HT turnover in the striatum of both sides. Contraversive rotations were positively correlated with dopamine content decreases and 5-HT turnover increases in the striatum ipsilateral to the infused substantia nigra. Backward walking was positively correlated with increased dopamine and 5-HT turnover in the striatum of the infused hemisphere. Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations. These behavioral effects of the neurotrophins are consistent with a concomitant activation of dopamine and 5-HT systems in vivo.

  12. COCAINE AMPHETAMINE REGULATED TRANSCRIPT%可卡因-苯丙胺调节转录肽

    Institute of Scientific and Technical Information of China (English)

    艾恒; 莫书荣; 路长林; 黄矛; 由振东

    2006-01-01

    可卡因-苯丙胺调节转录肽(cocaine amphetamine regulatedtranscript,CART肽)是一种在体内分布广泛的神经肽类物质.它具有广泛的生理作用,在奖赏与强化、进食与肥胖、精神焦虑行为、体液平衡、免疫功能、新陈代谢、内分泌以及其他的一些生理过程中均有作用.尤其CART肽在药物依赖中的作用研究使其自1981年发现以来迅速成为神经肽方面研究热点.

  13. Capillary gas-liquid chromatography separation of phenethylamines in amphetamine-positive urine samples.

    Science.gov (United States)

    DePace, A; Verebey, K; elSohly, M

    1990-11-01

    Good gas chromatography (GC) separation of molecules is essential for clean gas chromatography/mass spectrometry (GC/MS) confirmation of compounds. The trifluoro derivatives of ephedrine (E) and methamphetamine (MA) coelute on dimethyl silicone capillary columns, such as DB-1, which are most commonly used by chromatographers. Methods are described to separate E and MA to aid GC/MS confirmations of methamphetamine, ephedrine, or both E and MA together, whichever may be present in Enzyme Immunoassay (EIA)-analyzed amphetamine-positive urine samples. The use of the heptafluoro derivatives of E and MA on a DB-1 column, or the trifluoro derivatives of E and MA on a DB-17 column, is suggested for good gas chromatographic separation.

  14. Hallucinogens causing seizures? A case report of the synthetic amphetamine 2,5-dimethoxy-4-chloroamphetamine.

    Science.gov (United States)

    Burish, Mark J; Thoren, Katie L; Madou, Maura; Toossi, Shahed; Shah, Maulik

    2015-01-01

    Although traditional hallucinogenic drugs such as marijuana and lysergic acid diethylamide (LSD) are not typically associated with seizures, newer synthetic hallucinogenic drugs can provoke seizures. Here, we report the unexpected consequences of taking a street-bought hallucinogenic drug thought to be LSD. Our patient presented with hallucinations and agitation progressing to status epilepticus with a urine toxicology screen positive only for cannabinoids and opioids. Using liquid chromatography high-resolution mass spectrometry, an additional drug was found: an amphetamine-derived phenylethylamine called 2,5-dimethoxy-4-chloroamphetamine. We bring this to the attention of the neurologic community as there are a growing number of hallucinogenic street drugs that are negative on standard urine toxicology and cause effects that are unexpected for both the patient and the neurologist, including seizures.

  15. Stimulating a normal adjustment: misbehavior, amphetamines, and the electroencephalogram at the Bradley Home for children.

    Science.gov (United States)

    Bromley, Elizabeth

    2006-01-01

    This article uses an historical case study to describe the influence of social and contextual factors on the adoption of somatic approaches to children's misbehavior. The child guidance movement and the emergence of medicalized residential treatment facilities for children influenced the theoretical orientations of physicians treating children's behavior disorders in the United States in the 1930s. Charles Bradley and his colleagues at the Bradley Home in Rhode Island defined behavior disorders in social terms but investigated and treated misbehavior with somatic tools. The use of amphetamines and the electroencephalogram reorganized concepts of maladjustment along neurological lines, even as the research relied on the Home's social priorities. Electroencephalographic investigations especially shaped an organic concept of misbehavior. Ultimately, the somatic orientation obscured the central role of local context in Bradley Home physicians' research.

  16. Chiral analysis of amphetamines, methadone and metabolites in biological samples by electrodriven methods.

    Science.gov (United States)

    Mandrioli, Roberto; Mercolini, Laura; Raggi, Maria A

    2011-10-01

    Amphetamines and methadone are synthetic chiral drugs with a high potential for abuse. As such, several analytical methods have been developed for their enantioseparation and analysis in biological tissues, and some of these are based on electrodriven techniques. In this review, the most important and recent of these latter methods are reviewed and their main advantages and disadvantages are discussed. Particular attention is paid to the suitability of each method for the application to the biological matrix of interest: while all methods have been successfully applied for one or more biological tissues, to reach this goal they must overcome the sensitivity problem that is common to almost all capillary electrophoretic techniques. Most methods use one or more cyclodextrin derivatives as the chiral selector, thus the separation mechanism is not particularly complicated or unusual.

  17. Simultaneous determination of amphetamines and ketamines in urine by gas chromatography/mass spectrometry.

    Science.gov (United States)

    Lin, Huei Ru; Lua, Ahai Chang

    2006-01-01

    A method for the simultaneous determination of amphetamines and ketamines (ketamine, norketamine and dehydronorketamine) in urine samples by gas chromatography/mass spectrometry was developed and validated. Urine samples were extracted with organic solvent and derivatized with trifluoroacetic anhydride (TFAA). The limits of detection and limits of quantification for each analyte were lower than 19 and 30 ng/mL, respectively. Within-day and between-day precisions were within 0.5% and 10.6%, respectively. Biases for three levels of control samples were within -10.6% and +7.8%. The concentration of dehydronorketamine was greater than those of ketamine or norketamine in 19 of 35 ketamine-positive samples. A group of 110 human urine samples previously determined to contain at least one of the target analytes was analyzed using the new method, and excellent agreement was observed with previous results.

  18. Predicting hydration free energies of amphetamine-type stimulants with a customized molecular model

    Science.gov (United States)

    Li, Jipeng; Fu, Jia; Huang, Xing; Lu, Diannan; Wu, Jianzhong

    2016-09-01

    Amphetamine-type stimulants (ATS) are a group of incitation and psychedelic drugs affecting the central nervous system. Physicochemical data for these compounds are essential for understanding the stimulating mechanism, for assessing their environmental impacts, and for developing new drug detection methods. However, experimental data are scarce due to tight regulation of such illicit drugs, yet conventional methods to estimate their properties are often unreliable. Here we introduce a tailor-made multiscale procedure for predicting the hydration free energies and the solvation structures of ATS molecules by a combination of first principles calculations and the classical density functional theory. We demonstrate that the multiscale procedure performs well for a training set with similar molecular characteristics and yields good agreement with a testing set not used in the training. The theoretical predictions serve as a benchmark for the missing experimental data and, importantly, provide microscopic insights into manipulating the hydrophobicity of ATS compounds by chemical modifications.

  19. Analytical characterization of four new ortho-methoxybenzylated amphetamine-type designer drugs.

    Science.gov (United States)

    Westphal, Folker; Girreser, Ulrich; Waldmüller, Delia

    2016-09-01

    In a seizure of German custom authorities four N-(ortho-methoxybenzyl)amines with amphetamine partial structure were obtained as pure compounds: N-(ortho-methoxybenzyl)-3,4-dimethoxyamphetamine (3,4-DMA-NBOMe (1)), N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe (2)), N-(ortho-methoxybenzyl)-4-methylmethamphetamine (4-MMA-NBOMe (3)), and N-(ortho-methoxybenzyl)-5-(2-aminopropyl)benzofuran (5-APB-NBOMe (4)). The compounds have been detected in Germany for the first time and no analytical data had been previously published. Mass spectrometric (MS), infrared (IR) spectroscopic, and nuclear magnetic resonance (NMR) spectroscopic data are presented. Copyright © 2015 John Wiley & Sons, Ltd.

  20. LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum.

    Science.gov (United States)

    Wohlfarth, Ariane; Weinmann, Wolfgang; Dresen, Sebastian

    2010-04-01

    Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%.

  1. Segmental analysis of amphetamines in hair using a sensitive UHPLC-MS/MS method.

    Science.gov (United States)

    Jakobsson, Gerd; Kronstrand, Robert

    2014-06-01

    A sensitive and robust ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxy methamphetamine in hair samples. Segmented hair (10 mg) was incubated in 2M sodium hydroxide (80°C, 10 min) before liquid-liquid extraction with isooctane followed by centrifugation and evaporation of the organic phase to dryness. The residue was reconstituted in methanol:formate buffer pH 3 (20:80). The total run time was 4 min and after optimization of UHPLC-MS/MS-parameters validation included selectivity, matrix effects, recovery, process efficiency, calibration model and range, lower limit of quantification, precision and bias. The calibration curve ranged from 0.02 to 12.5 ng/mg, and the recovery was between 62 and 83%. During validation the bias was less than ±7% and the imprecision was less than 5% for all analytes. In routine analysis, fortified control samples demonstrated an imprecision hair demonstrated an imprecision forensic hair samples previously analyzed with an ultra high performance liquid chromatography time of flight mass spectrometry (UHPLC-TOF-MS) screening method. The proposed method was suitable for quantification of these drugs in forensic cases including violent crimes, autopsy cases, drug testing and re-granting of driving licences. This study also demonstrated that if hair samples are divided into several short segments, the time point for intake of a small dose of amphetamine can be estimated, which might be useful when drug facilitated crimes are investigated.

  2. The Histaminergic Tuberomamillary Nucleus Is Involved in Appetite for Sex, Water and Amphetamine.

    Directory of Open Access Journals (Sweden)

    Marco Contreras

    Full Text Available The histaminergic system is one component of the ascending arousal system which is involved in wakefulness, neuroendocrine control, cognition, psychiatric disorders and motivation. During the appetitive phase of motivated behaviors the arousal state rises to an optimal level, thus giving proper intensity to the behavior. Previous studies have demonstrated that the histaminergic neurons show an earlier activation during the appetitive phase of feeding, compared to other ascending arousal system nuclei, paralleled with a high increase in arousal state. Lesions restricted to the histaminergic neurons in rats reduced their motivation to get food even after 24 h of food deprivation, compared with intact or sham lesioned rats. Taken together, these findings indicate that the histaminergic system is important for appetitive behavior related to feeding. However, its role in other goal-directed behaviors remains unexplored. In the present work, male rats rendered motivated to obtain water, sex, or amphetamine showed an increase in Fos-ir of histaminergic neurons in appetitive behaviors directed to get those reinforcers. However, during appetitive tests to obtain sex, or drug in amphetamine-conditioned rats, Fos expression increased in most other ascending arousal system nuclei, including the orexin neurons in the lateral hypothalamus, dorsal raphe, locus coeruleus and laterodorsal tegmental neurons, but not in the ventral tegmental area, which showed no Fos-ir increase in any of the 3 conditions. Importantly, all these appetitive behaviors were drastically reduced after histaminergic cell-specific lesion, suggesting a critical contribution of histamine on the intensity component of several appetitive behaviors.

  3. Calcium channel antagonists suppress cross-tolerance to the anxiogenic effects of D-amphetamine and nicotine in the mouse elevated plus maze test.

    Science.gov (United States)

    Biala, Grazyna; Kruk, Marta

    2008-01-01

    The purpose of the current experiments was to examine the anxiety-related effects of repeated amphetamine and nicotine administration using the mouse elevated plus maze (EPM). d-amphetamine was administered daily for 8 days (2 mg/kg, i.p.). On the 9th day, mice were challenged with amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.), and were tested 30 min after this last injection. Additionally, a distinct group of mice was pretreated with nicotine (0.1 mg/kg, s.c., 6 days). These mice were subjected to nicotine (0.1 mg/kg, s.c.) or amphetamine (2 mg/kg, i.p.) challenge on the seventh day to see if full crossover effects developed after the pretreatment of both psychostimulant drugs. Moreover, the L-type voltage-dependent calcium channel antagonists nimodipine (5 and 10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5 and 10 mg/kg, i.p.) and diltiazem (5 and 10 mg/kg, i.p.) were injected prior to each injection of chronic d-amphetamine or nicotine. We observed cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine that was blunted by a pretreatment with calcium channel blockers. Overall our findings imply that similar neural calcium-dependent mechanisms are involved in the anxiety-related responses to chronic amphetamine and nicotine injections. As anxiety seems to be an important factor for the development of psychostimulant dependence, the L-type VDCC antagonists can offer an interesting approach for the pharmacotherapy of addiction, including amphetamine and/or nicotine dependence.

  4. Effects of d-amphetamine on short- and long-term memory in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley rats.

    Science.gov (United States)

    Meneses, A; Ponce-Lopez, T; Tellez, R; Gonzalez, R; Castillo, C; Gasbarri, A

    2011-01-01

    Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.

  5. The Anorexigenic Peptide Neuromedin U (NMU Attenuates Amphetamine-Induced Locomotor Stimulation, Accumbal Dopamine Release and Expression of Conditioned Place Preference in Mice.

    Directory of Open Access Journals (Sweden)

    Daniel Vallöf

    Full Text Available Amphetamine dependence, besides its substantial economical consequence, is a serious cause of mortality and morbidity. By investigations of the neurochemical correlates through which addictive drugs, such as amphetamine, activate the mesoaccumbal dopamine system unique targets for treatment of drug addiction can be identified. This reward link consists of a dopamine projection from the ventral tegmental area to the nucleus accumbens (NAc suggesting that these brain areas are important for reward. The physiological function of gut-brain peptides has expanded beyond food intake modulation and involves regulation of drug reinforcement. A novel candidate for reward regulation is the anorexigenic peptide neuromedin U (NMU. We therefore investigated the effects of intracerebroventricular (icv administration of NMU on amphetamine's well-documented effects on the mesoaccumbal dopamine system, i.e. locomotor stimulation and accumbal dopamine release in mice. In addition, the effect of accumbal NMU administration on locomotor activity was examined. The effect of NMU, icv or intra-NAc, on the expression of conditioned place preference (CPP was elucidated. Firstly, we showed that icv administration of NMU attenuate the amphetamine-induced locomotor stimulation, accumbal dopamine release and expression of CPP in mice. Secondly, we found that a lower dose of NMU (icv reduce the amphetamine-induced locomotor stimulation in mice. Thirdly, we demonstrated that NMU administration into the NAc block the ability of amphetamine to cause a locomotor stimulation in mice. However, accumbal NMU administration did not attenuate the amphetamine-induced expression of CPP in mice. Our novel data suggest that central NMU signalling is involved in development of amphetamine dependence.

  6. The role of BDNF/TrkB signaling in acute amphetamine-induced locomotor activity and opioid peptide gene expression in the rat dorsal striatum

    Directory of Open Access Journals (Sweden)

    Jacqueline F McGinty

    2011-07-01

    Full Text Available Exposure to psychostimulants increases brain-derived neurotrophic factor (BDNF mRNA and protein levels in the cerebral cortex and subcortical structures. Because BDNF is co-localized with dopamine and glutamate in afferents to the striatum of rats, it may be co-released with those neurotransmitters upon stimulation. Further, there may be an interaction between the intracellular signaling cascades activated by dopamine, glutamate, and TrkB receptors in medium spiny striatal neurons. In the present study, the effect of acute amphetamine administration on TrkB phosphorylation (p-TrkB, as an indirect indicator of activation, and striatal gene expression, was evaluated. In Experiment 1, 15 minutes or 2 hours after a single saline or amphetamine (2.5 mg/kg, i.p. injection, the caudate-putamen (CPu, nucleus accumbens (NAc, and dorsomedial prefrontal cortex (dmPFC were extracted and processed for phospho (p-TrkB immunoreactivity. Immunoprecipitation analyses indicated that neither the tyrosine phosphorylation (p-Tyr or autophosphorylation sites of TrkB (706 were changed in NAc, CPu, or dmPFC 15 min after amphetamine administration. In contrast, p-Tyr and the PLCγ phosphorylation site of TrkB (816 were increased in the NAc and CPu 2 hrs after amphetamine. In Experiment 2, intra-striatal infusion of the tyrosine kinase inhibitor, K252a, increased amphetamine-induced vertical activity but not total distance traveled. In addition, K252a inhibited amphetamine -induced preprodynorphin, but not preproenkephalin, mRNA expression in the striatum. These data indicate that acute amphetamine administration induces p-TrkB activation and signaling in a time- and brain region-dependent manner and that TrkB/BDNF signaling plays an important role in amphetamine-induced behavior and striatal gene expression.

  7. Amphetamine and N-acetylamphetamine incorporation into hair: an investigation of the potential role of drug basicity in hair color bias.

    Science.gov (United States)

    Borges, C R; Wilkins, D G; Rollins, D E

    2001-01-01

    To elucidate the role of drug basicity in the preferential incorporation of certain drugs into dark hair rather than light hair, Long-Evans rats were dosed with amphetamine or its non-basic analogue N-acetylamphetamine (N-AcAp) and their hair evaluated for drug content. Rats were shaved prior to dosing. On the 14th day after dosing, hair from the same area that was shaved prior to dosing was shaved and collected. After the addition of amphetamine-d3 or N-AcAp-d3 as an internal standard, hair samples (20 mg) were digested in 1M NaOH at 37 degrees C. Digested solutions were then extracted with n-butyl chloride/chloroform (4:1, v/v). After drying and reconstituting, samples were injected onto a ThermoQuest TSQ liquid chromatography-tandem mass spectrometry instrument for analysis. Black hair from rats dosed with amphetamine (n = 8) was found to contain 6.44 +/- 1.31 (SD) ng amphetamine/mg hair. White hair from the same rats contained 2.04 +/- 0.58 ng amphetamine/mg hair. In contrast, no difference in N-AcAp content was found between black hair (0.87 +/- 0.08 ng N-AcAp/mg hair) and white hair (0.83 +/- 0.15 ng N-AcAp/mg hair) from rats dosed with N-AcAp (n = 8).

  8. Development and validation of two LC-MS/MS methods for the detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine using turbulent flow chromatography.

    Science.gov (United States)

    Schaefer, Nadine; Peters, Benjamin; Schmidt, Peter; Ewald, Andreas H

    2013-01-01

    In the context of driving ability diagnostics in Germany, administrative cutoffs for various drugs and pharmaceuticals in urine have been established. Two liquid chromatography-tandem mass spectrometry methods for simultaneous detection and quantification of amphetamines, designer amphetamines, benzoylecgonine, benzodiazepines, opiates, and opioids in urine were developed and validated. A 500-μL aliquot of urine was diluted and fortified with an internal standard solution. After enzymatic cleavage, online extraction was performed by an ion-exchange/reversed-phase turbulent flow column. Separation was achieved by using a reversed-phase column and gradient elution. For detection, a Thermo Fisher TSQ Quantum Ultra Accurate Mass tandem mass spectrometer with positive electrospray ionization was used, and the analytes were measured in multiple-reaction monitoring mode detecting two transitions per precursor ion. The total run time for both methods was about 15 min. Validation was performed according to the guidelines of the Society of Toxicological and Forensic Chemistry. The results of matrix effect determination were between 78% and 116%. The limits of detection and quantification for all drugs, except zopiclone, were less than 10 ng/mL and less than 25 ng/mL, respectively. Calibration curves ranged from 25 to 200 ng/mL for amphetamines, designer amphetamines, and benzoylecgonine, from 25 to 250 ng/mL for benzodiazepines, from 12.5 to 100 ng/mL for morphine, codeine, and dihydrocodeine, and from 5 to 50 ng/mL for buprenorphine and norbuprenorphine. Intraday and interday precision values were lower than 15%, and bias values within ± 15% were achieved. Turbulent flow chromatography needs no laborious sample preparation, so the workup is less time-consuming compared with gas chromatography-mass spectrometry methods. The methods are suitable for quantification of multiple analytes at the cutoff concentrations required for driving ability diagnostics in Germany.

  9. Prevalence of use study for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxy-methamphetamine (MDMA), and 3,4-methylenedioxy-ethylamphetamine (MDEA) in military entrance processing stations (MEPS) specimens.

    Science.gov (United States)

    Klette, Kevin L; Kettle, Aaron R; Jamerson, Matthew H

    2006-06-01

    The Roche Abuscreen Onlinetrade mark Amphetamine immunoassay (IA), modified to include sodium periodate, and the Microgenics DRI Ecstasy IA were used to determine the prevalence of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA) in urine specimens from applicants seeking to join the United States Armed Forces. Over a 4-month period, a total of 85,658 specimens were IA screened using the Department of Defense 500 ng/mL administrative cutoff level for AMP and MDMA. All presumptively positive specimens were confirmed using a solid-phase extraction procedure coupled with simultaneous analysis of AMP, MAMP, MDA, MDMA, and MDEA by fast gas chromatography-mass spectrometry using the same cutoff levels as the IA. The Roche Online Amphetamine IA identified 216 specimens as presumptively positive; of these, 70 specimens confirmed positive for AMP and 87 specimens confirmed positive for AMP and/or MAMP, resulting in a confirmation rate of 73%. The Microgenics DRI Ecstasy IA identified eight specimens as presumptively positive; of these, five specimens confirmed positive for MDMA and/or MDA, resulting in a confirmation rate of 63%. The total use prevalence for AMP, MAMP, MDA, MDMA, and/or MDEA in military entrance processing stations specimens over the testing period was determined to be 0.19%.

  10. [Effect of chlorpromazine and amphetamine on incidental memory and its relation to the introvert-extravert structure of personality].

    Science.gov (United States)

    Zaimov, K; Kokoshkarova, A

    1978-10-01

    A total of fifty-four test subjects divided into one control group and two experimental groups were used to study the effects of chlorpromazine and amphetamine upon the incidental memory, its accuracy, and possible dependence on the introversive or extroversive personality structure, respectively. It has been found that chlorpromazine tends to lessen the incidental memory in extent and increase the number of allomnesias or instances of inaccurate remembrance, whereas amphetamine has the effects of increasing the extent of the incidental memory and reducing the number of allomnesias. A comparison of the extent of the incidental memory with the structure of personality in respect of introversion or extroversion in the control group also showed significant differences, the incidental memory being of smaller extent in the case of introversion and greater extent in the case of extroversion.

  11. Measurement uncertainty for the determination of amphetamines in urine by liquid-phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Franco de Oliveira, Sarah Carobini Werner de Souza Eller; Yonamine, Mauricio

    2016-08-01

    A gas chromatography-mass spectrometry method for the determination of amphetamines in urine samples by means of liquid-phase microextraction was validated, including calculation of measurement uncertainty. After extraction in the three-phase mode, acceptor phase was withdrawn from the fiber and the residue was derivatized with trifluoroacetic anhydride. The method showed to be very simple, rapid and it required a significantly low amount of organic solvent for extraction. The limits of detection were 10 and 20μg/L for amphetamine and methamphetamine, respectively. The calibration curves were linear over the specified range (20μg/L to 1400μg/L; r(2)>0.99). The method showed to be both precise and accurate and a relative combined uncertainty of 2% was calculated. In order of importance, the factors which were more determinant for the calculation of method uncertainty were: analyte concentration, sample volume, trueness and method precision.

  12. Performance characteristics of DRI, CEDIA, and REMEDi systems for preliminary tests of amphetamines and opiates in human urine.

    Science.gov (United States)

    Huang, Min-Kun; Dai, Yu-Shan; Lee, Choung-Huei; Liu, Chiareiy; Tsay, Wen-Ing; Li, Jih-Heng

    2006-01-01

    Arrestee urine specimens (930) were tested with DRI, CEDIA, and REMEDi; those that tested positive for amphetamines and opiates (616 and 414, respectively) were then confirmed by gas chromatography-mass spectrometry. The performance characteristics of these three preliminary systems were evaluated using the following commonly used parameters: true positive, true negative, false positive, and false negative. The sensitivity, specificity, and efficiency of these methods were also calculated. Data derived from this study indicated DRI and CEDIA adapted by this study generated acceptable preliminary test results for amphetamine/methamphetamine and morphine/codeine, but not for MDA/MDMA and REMEDi has lower sensitivity than DRI and CEDIA, but with better specificity and efficiency, supporting its use under emergency room settings where drug concentrations in overdose cases are expectedly at high levels.

  13. Cocaine and amphetamine elicit differential effects in rats with a unilateral injection of dopamine transporter antisense oligodeoxynucleotides.

    Science.gov (United States)

    Silvia, C P; Jaber, M; King, G R; Ellinwood, E H; Caron, M G

    1997-02-01

    We have developed an antisense oligodeoxynucleotide to the dopamine transporter and used it to discriminate the behavioral properties of amphetamine and cocaine. In SK-N-MC cells permanently transfected with the dopamine transporter complementary DNA, treatment with 5 mM antisense oligodeoxynucleotide reduced dopamine uptake by 25% when compared to sense control. Unilateral intranigral administration of dopamine transporter antisense (50 microM) twice daily in freely moving rats for 2.5 days was sufficient to reduce dopamine transporter messenger RNA by 70% as measured by in situ hybridization, but not protein levels as measured by [3H]mazindol binding. However, intranigral treatment via implanted osmotic minipump over a period of seven days produced reductions in both dopamine transporter messenger RNA and protein levels (32%) at a dose of 500 pmol/day. These results indicate a longer half-life for the dopamine transporter than expected. Potassium chloride depolarization of ipsilateral striatal slices showed a greater than 200% increase in dopamine overflow on the antisense-treated side compared to the control side. Since imbalance of dopamine tone is known to induce rotational activity, we tested this behavioral paradigm in rats treated with various oligodeoxynucleotides at different doses and time-points. We have found that antisense-treated animals did not rotate spontaneously under any experimental conditions. Using various psychostimulants that target the dopamine transporter and increase dopamine levels, we found that the antisense-treated animals consistently rotated contralaterally in response to amphetamine (2 mg/kg), but not to cocaine (10 mg/kg) or nomifensine (10 mg/kg). These results bring in vivo evidence for a different mode of action of amphetamine and cocaine on the dopamine transporter and lend direct support to the view that amphetamine acts as a dopamine releaser, whereas cocaine acts by blocking dopamine transport.

  14. On-line derivatization gas chromatography with furan chemical ionization tandem mass spectrometry for screening of amphetamines in urine.

    Science.gov (United States)

    Tzing, Shin-Hwa; Ghule, Anil; Liu, Jen-Yu; Ling, Yong-Chien

    2006-12-22

    A simple alternative method with minimal sample pretreatment is investigated for screening of amphetamines in small volume (using only 20 microL) of urine sample. The method is sensitive and selective. The method uses gas chromatography (GC) direct sample introduction (DSI) for on-line derivatization (acylation) of amphetamines to improve sensitivity. Furan as chemical ionization (CI) reagent in conjunction with tandem mass spectrometry (MS/MS) is used to improve selectivity. Low background with sharp protonated molecular ion peaks of analytes is the evidence of improvement in sensitivity and selectivity. Blank urine samples spiked with known amounts of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine and 3,4-methylenedioxyethylamphetamine is analyzed. Selected ion monitoring of the characteristic product ions (m/z 119+136+150+163) using furan CI-MS/MS in positive ion mode is used for quantification. Limits of detection (LOD) between 0.4 and 1.0 ng mL(-1) and limits of quantitation (LOQ) between 1.0 and 2.0 ng mL(-1) are established. Linear response over the range of 1-1000 ng mL(-1) (r(2)>0.997) is observed for all analytes, except for methamphetamine (2.0-1000 ng mL(-1)). Good accuracy between 86 and 113% and precision ranging from 4 to 18% is obtained. The method is also tested on real samples of urine from suspected drug abusers. This method could be used for screening and determination of amphetamines in urine samples, however needs additional work for full validation.

  15. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenylalkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    OpenAIRE

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB), 3,4-methylenedioxyamphetamine (MDA), and 3,4-(methylenedioxyphenyl)-2-butanamine (BDB), are widely abused as psychedelics. In this paper, these compounds were derivatized with trifluoroacetic (TFA) anhydride and analyzed by gas chromatography/mass sp...

  16. Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.

    Science.gov (United States)

    Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérèse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C

    2012-11-01

    Trace amines (TAs) such as β-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s).

  17. Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning.

    Science.gov (United States)

    Dwyer, Dominic M; Boakes, Robert A; Hayward, Andrew J

    2008-10-01

    Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.

  18. Simultaneous quantification of amphetamine, opiates, ketamine and relative metabolites in urine for confirmatory analysis by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Lin, Huei-Ru; Choi, Ka-Ian; Lin, Tzu-Chieh; Hu, Anren

    2013-06-15

    The rise in amphetamine, ketamine and opiates abuse in Taiwan has created a need for a reliable confirmatory assay. A method that combines superficially porous liquid chromatography tandem mass spectrometry (LC-MS/MS) with solid-phase extraction (SPE) was developed for the simultaneous quantification of amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), ketamine, opiates, and their corresponding metabolites in urine. The total run time of the method was 6.7min including equilibration time. The method was validated in accordance with the European Commission (EC) Decision 2002/642/EC. The within- and between-day precision was below 13.6% and the accuracy ranged from -17.1% to +9.9% for all analytes. Ion suppression was observed but compensated by using deuterated internal standards. No carryover was detected and the analytes were stable at room temperature for 16h, and for 72h at 4°C, and three-thaw cycles. The method was further validated by comparison with a reference gas chromatography-mass spectrometry (GC-MS) method, using 52 authentic urine samples. The results indicated that for the target analytes studied, the LC-MS/MS analysis was as precise, accurate, and specific as the GC-MS method. In conclusion, the present LC-MS/MS method is robust and reliable, and suitable for use as a confirmation assay in the simultaneous urine drug testing and quantification of amphetamines, ketamines, and opiates.

  19. Simultaneous determination of HFBA-derivatized amphetamines and ketamines in urine by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Lee, Hei Hwa; Lee, Jong Feng; Lin, Sin Yu; Chen, Ping Ho; Chen, Bai Hsiun

    2011-04-01

    To facilitate the analysis of targeted drugs under high sample volume testing environment, an extraction, derivatization and gas chromatographic-mass spectrometric analysis method was developed for simultaneously determination of amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyethylamphetamine (MDEA), ketamine, and norketamine in urine. This method utilized solid-phase extraction in conjunction with derivatization using heptafluorobutyric anhydride (HFBA) as the derivatization reagent. Using a 1-mL sample, the limits of quantitation achieved for the analysis of AMP, MAMP, MDA, MDMA, MDEA, ketamine, and norketamine were 25, 15, 60, 60, 70, 25, and 30 ng/mL, respectively. Upper limits of quantitation were 8000 ng/mL for all amphetamines and 6000 ng/mL for ketamine and norketamine. Except for dehydronorketamine (DHNK), within-day and between-day precisions (as expressed in CV%) for quality control samples were ≤ 3.1% and ≤ 4.95%, respectively. Except DHNK, the within-day accuracy ranged between 96.0% and 110.7% and the between-day accuracy ranged between 96.9% and 108.7%. A group of 107 urine samples previously determined to contain the target analytes were analyzed by this new approach. Quantitative data produced by both methods agreed well. With this new approach, we were able to use a single analytical protocol to conduct the confirmation test for samples that preliminarily tested positive (by immunoassay) for amphetamines, ketamine, or both.

  20. Ultra-performance liquid chromatography-tandem mass spectrometry method for the analysis of amphetamines in plasma.

    Science.gov (United States)

    Fernández, María del Mar Ramírez; Samyn, Nele

    2011-10-01

    A fast and selective ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS-MS) method for the determination of amphetamines (amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, ephedrine, and p-methoxyamphetamine) in plasma has been developed and validated. Sample preparation was performed by liquid-liquid extraction using ethyl acetate. For optimized chromatographic performance with repeatable retention times, narrow and symmetrical peaks, and focusing all analytes at the column inlet, a gradient start, with acid mobile phase consisting of 0.1% formic acid and methanol was chosen. Positive electrospray ionization MS-MS detection was performed with two multiple reaction monitoring transitions for each analyte. Deuteriumlabeled internal standards were used for five of the analytes. The limit of detection was in the range 0.25-1.25 ng/mL, and the limit of quantification was fixed at the lowest calibrator of 2.5 ng/mL for all of the compounds. The RSD values of the intra- and interassay precision and accuracy were lower than 11% at four concentration levels, including two external quality controls. No or only minor matrix effects were observed, and the extraction method presented recoveries higher than 93% for all the compounds. Total run time, including equilibration, was 12 min. The method is routinely used at the National Institute of Criminalistics and Criminology for quantitative determination of the main amphetamines in plasma from forensic and driving under the influence cases.

  1. Rapid screening method for determination of Ecstasy and amphetamines in urine samples using gas chromatography-chemical ionisation mass spectrometry.

    Science.gov (United States)

    Pellegrini, M; Rosati, F; Pacifici, R; Zuccaro, R; Romolo, F S; Lopez, A

    2002-04-05

    The need for analytical screening tests more reliable and valid to detect amphetamine and related "designer drugs" in biological samples is becoming critical, due to the increasing diffusion of these drugs on the European illegal market. The most common screening procedures based on immunoassays suffer a number of limitations, including low sensitivity, lack of specificity and limited number of detectable substances. This paper describes a screening method based on gas-chromatography-mass-spectrometry (GC/MS) using positive chemical ionisation (PCI) detection. Methanol was used as reactant gas in the ionisation chamber. Molecular ions of different compounds were monitored, allowing a sensitivity of 5-10 ng/ml with high selectivity. The sensitivity of the method gives positive results in samples taken 48-72 h after intake of one dose of 50-100 mg. The method is simple and rapid. Sample preparation was limited to one liquid-liquid extraction, without any hydrolysis and derivatisation. Hydrolysis is critical to identify metabolites excreted as conjugates. Blank urine samples spiked with known amounts of amphetamine (AM), methylamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethylamphetamine (MDMA), methylenedioxyethylamphetamine (MDEA) and methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) were analysed. The method was successfully tested on real samples of urine from people, whose use of amphetamine was suspected, and results were compared with results obtained with immunoassays.

  2. Another look at amphetamine-induced stereotyped locomotor activity in rats using a new statistic to measure locomotor stereotypy.

    Science.gov (United States)

    Mueller, K; Hollingsworth, E M; Cross, D R

    1989-01-01

    Rat open field behavior is often used as a tool to study the behavioral effects of drugs. In this report, drug-induced patterns of locomotion in an open field were studied with the aid of a simple new statistic. Briefly, the animal's path through the open field is converted into a series of trips. Gamma (gamma) estimates the probability that the animal will repeat the trip that it has just exhibited; thus gamma quantifies "locomotor stereotypy". Trip lengths can also be compared across drug groups. Thus caffeine has no effect on gamma even though it produces a dose-related increase in locomotions. Caffeine does not produce amphetamine-like stereotypy. On the other hand, amphetamine produces a dose-related increase in gamma. Although gamma was designed to detect any pattern of locomotor behavior, rats treated with high doses of amphetamine almost always exhibited the same pattern of locomotor behavior - repetitive trips around the perimeter of the open field. Although further characterization of the statistic is necessary, these findings suggest that gamma has potential for quantifying "locomotor stereotypy" and for providing a more subtle description of locomotor behavior in general.

  3. Evaluation of commercial multi-drug oral fluid devices to identify 39 new amphetamine-designer drugs.

    Science.gov (United States)

    Nieddu, Maria; Burrai, Lucia; Trignano, Claudia; Boatto, Gianpiero

    2014-03-01

    Recently, the diffusion on the black market of new psychoactive substances not controlled and often sold as 'legal highs', is exponentially increasing in Europe. Generally, the first analysis for these drugs involves an immunoassay screening in urine or plasma. Actually, there is growing interest in the use of oral fluid (OF) as alternative specimen over conventional biological fluids for drug testing, because of the significant advantages, as a non-invasive collection under direct observation without undue embarrassment or invasion of privacy, and a good correlation with plasma analytical data. Few assays have been developed for detection of new psychoactive compounds in biological samples, so it is important to investigate how they may or may not react in pre-existing commercial immunoassays. In this paper, two different multi-drugs oral fluid screen devices (OFDs) (Screen® Multi-Drug OFD and GIMA One Step Multi-Line Screen Test OFD) were evaluated to determine the cross-reactivity of thirty-nine new amphetamine designer drugs, including twelve substances officially recognized as illicit by italian legislation. Cross-reactivity towards most drugs analyzed was <1 in assays targeting amphetamine (AMP) or methamphetamine (MET). Only two (p-methoxyamphetamine and p-methoxymethamphetamine) of all tested amphetamines gave a positive result.

  4. Comparison and evaluation of DRI methamphetamine, DRI ecstasy, Abuscreen ONLINE amphetamine, and a modified Abuscreen ONLINE amphetamine screening immunoassays for the detection of amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA) in human urine.

    Science.gov (United States)

    Stout, Peter R; Klette, Kevin L; Wiegand, Russell

    2003-01-01

    The performances of four immunoassays (DRI amphetamines, DRI ecstasy, Abuscreen ONLINE amphetamines, and a modified Abuscreen ONLINE amphetamines) were evaluated for control failure rates, sensitivity, and specificity for amphetamine (AMP), methamphetamine (MTH), 3,4-methylenedioxyamphetamine (MDA), and 3,4-methylenedioxymethamphetamine (MDMA). The two DRI reagents and the ONLINE reagents were run according to manufacturer specifications using a Roche Hitachi Modular DDP system. The modified ONLINE reagent was calibrated with MDMA and had 16mM sodium periodate added to the R2 reagent. These assays were run on approximately 27,500 human urine samples and 7000 control urine samples prepared at 350 and 674 ng/mL over the course of 8 days. All assays were calibrated using a single point, qualitative cutoff standard with the manufacturer-recommended compound at the Department of Defense cutoff (500 ng/mL). Gas chromatography-mass spectrometry (GC-MS) confirmation was conducted on screened-positive samples. Control performance for the manufacturer recommended assays was excellent, with a maximum qualitative control failure rate of 2.03%. The modified ONLINE reagent demonstrated poor control performance with a maximum failure rate of 38.3% and showed no improved MDMA sensitivity when compared with the ONLINE reagent; the confirmation rate (20%) was improved when compared with the production ONLINE reagent (8%). The DRI ecstasy reagent provided improved sensitivity for MDMA as compared with the ONLINE reagent, with approximately 23% more samples screening and confirming positive for MDMA and a confirmation rate of approximately 90%. The DRI methamphetamine reagent had a low confirmation rate (6% or less) and produced numerous positives for samples with only ephedrine or pseudoephedrine present.

  5. Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine in rats

    Directory of Open Access Journals (Sweden)

    Martin eZack

    2014-02-01

    Full Text Available Addiction is considered to be a brain disease caused by chronic exposure to drugs. Sensitization of brain dopamine (DA systems partly mediates this effect. Pathological gambling (PG is considered to be a behavioral addiction. Therefore, PG may be caused by chronic exposure to gambling. Identifying a gambling-induced sensitization of DA systems would support this possibility. Gambling rewards evoke DA release. One episode of slot machine play shifts the DA response from reward delivery to onset of cues (spinning reels for reward, in line with temporal difference learning principles. Thus, conditioned stimuli (CS play a key role in DA responses to gambling. In primates, DA response to a CS is strongest when reward probability is 50%. Under this schedule the CS elicits an expectancy of reward but provides no information about whether it will occur on a given trial. During gambling, a 50% schedule should elicit maximal DA release. This closely matches reward frequency (46% on a commercial slot machine. DA release can contribute to sensitization, especially for amphetamine. Chronic exposure to a CS that predicts reward 50% of the time could mimic this effect. We tested this hypothesis in 3 studies with rats. Animals received 15 x 45-min exposures to a CS that predicted reward with a probability of 0, 25, 50, 75 or 100%. The CS was a light; the reward was a 10% sucrose solution. After training, rats received a sensitizing regimen of 5 separate doses (1 mg/kg of d-amphetamine. Lastly they received a 0.5 or 1 mg/kg amphetamine challenge prior to a 90-min locomotor activity test. In all 3 studies the 50% group displayed greater activity than the other groups in response to both challenge doses. Effect sizes were modest but consistent, as reflected by a significant group x rank association ( = .986, p = .025. Chronic exposure to a gambling-like schedule of reward predictive stimuli can promote sensitization to amphetamine much like exposure to

  6. Role of cocaine- and amphetamine-regulated transcript in estradiol-mediated neuroprotection

    Science.gov (United States)

    Xu, Yun; Zhang, Wenri; Klaus, Judith; Young, Jennifer; Koerner, Ines; Sheldahl, Laird C.; Hurn, Patricia D.; Martínez-Murillo, Francisco; Alkayed, Nabil J.

    2006-09-01

    Estrogen reduces brain injury after experimental cerebral ischemia in part through a genomic mechanism of action. Using DNA microarrays, we analyzed the genomic response of the brain to estradiol, and we identified a transcript, cocaine- and amphetamine-regulated transcript (CART), that is highly induced in the cerebral cortex by estradiol under ischemic conditions. Using in vitro and in vivo models of neural injury, we confirmed and characterized CART mRNA and protein up-regulation by estradiol in surviving neurons, and we demonstrated that i.v. administration of a rat CART peptide is protective against ischemic brain injury in vivo. We further demonstrated binding of cAMP response element (CRE)-binding protein to a CART promoter CRE site in ischemic brain and rapid activation by CART of ERK in primary cultured cortical neurons. The findings suggest that CART is an important player in estrogen-mediated neuroprotection and a potential therapeutic agent for stroke and other neurodegenerative diseases. ischemia | stroke | estrogen

  7. Maternal separation altered behavior and neuronal spine density without influencing amphetamine sensitization.

    Science.gov (United States)

    Muhammad, Arif; Kolb, Bryan

    2011-09-30

    We studied the long-term influence of maternal separation (MS) on periadolescent behavior, adult amphetamine (AMPH) sensitization, and structural plasticity in the corticolimbic regions in rats. Male and female pups, separated daily for 3h from the dam during postnatal day 3-21, were tested for periadolescent exploratory, emotional, cognitive, and social behaviors. The development and persistence of drug-induced behavioral sensitization were tested by repeated AMPH administration and a challenge, respectively. The spine density was examined in the nucleus accumbens (NAc), the medial prefrontal cortex (mPFC), and the orbital frontal cortex (OFC) from Golgi-Cox stained neurons. The results showed that MS enhanced anxiety-like behavior in males. MS abolished the sex difference in playful attacks observed in controls with resultant feminization of male play behavior. Furthermore, the probability of complete rotation defense to face an attack was decreased in females. AMPH administration resulted in the development of behavioral sensitization that persisted at least for two weeks. Sensitization was not influenced by MS. MS increased the spine density in the NAc, the mPFC, and the OFC. Repeated AMPH administration increased the spine density in the NAc and the mPFC, and decreased it in the OFC. MS blocked the drug-induced alteration in these regions. In sum, MS during development influenced periadolescent behavior in males, and structurally reorganized cortical and subcortical brain regions without affecting AMPH-induced behavioral sensitization.

  8. Immunodetection of cocaine- and amphetamine-regulated transcript in bovine pancreas.

    Science.gov (United States)

    Janiuk, Izabela; Młynek, Krzysztof

    2015-07-01

    This study was aimed at identifying and determining the configuration of structures which contain the cocaine- and amphetamine-regulated transcript peptide (CART) in the bovine pancreas. The study material was collected from 20 animals. The distribution of CART in the bovine pancreas was investigated, by an immunohistochemical evaluation. CART peptide in the normal pancreas has been identified in intrapancreatic ganglia, nerve fibres and in endocrine cells of Langerhans islets and exocrine pancreas. CART immunoreactive nerve fibres innervate the exocrine and endocrine regions and the intrapancreatic ganglia, where they form a moderate number of networks, encircling the cell bodies. The few CART-immunoreactive endocrine cells, that appear in the bovine pancreas, are not limited to the islet cells, where they form a subpopulation of CART-containing cells, but are also individually distributed in the exocrine region. Furthermore, CART has been visualized in nerve fibres, innervating pancreatic outlet ducts and blood vessels. CART plays a physiological role in the integrated mechanisms that regulate both endocrine and exocrine pancreatic secretion. These results are consistent with the hypothesis that CART expression in nerve fibres and intrapancreatic ganglia is a common feature of the mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to single cells of the bovine pancreas.

  9. Objective and subjective cognitive enhancing effects of mixed amphetamine salts in healthy people.

    Science.gov (United States)

    Ilieva, Irena; Boland, Joseph; Farah, Martha J

    2013-01-01

    Psychostimulants such as mixed amphetamine salts (MAS, brand name Adderall) are widely used for cognitive enhancement by healthy young people, yet laboratory research on effectiveness has yielded variable results. The present study assessed the effects of MAS in healthy young adults with an adequately powered double-blind cross-over placebo-controlled trial. We examined effects in 13 measures of cognitive ability including episodic memory, working memory, inhibitory control, convergent creativity, intelligence and scholastic achievement, with the goals of determining (1) whether the drug is at least moderately enhancing (Cohen's d >= .5) to some or all cognitive abilities tested, (2) whether its effects on cognition are moderated by baseline ability or COMT genotype, and (3) whether it induces an illusory perception of cognitive enhancement. The results did not reveal enhancement of any cognitive abilities by MAS for participants in general. There was a suggestion of moderation of enhancement by baseline ability and COMT genotype in a minority of tasks, with MAS enhancing lower ability participants on word recall, embedded figures and Raven's Progressive Matrices. Despite the lack of enhancement observed for most measures and most participants, participants nevertheless believed their performance was more enhanced by the active capsule than by placebo. We conclude that MAS has no more than small effects on cognition in healthy young adults, although users may perceive the drug as enhancing their cognition. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

  10. Sodium butyrate reverses the inhibition of Krebs cycle enzymes induced by amphetamine in the rat brain.

    Science.gov (United States)

    Valvassori, Samira S; Calixto, Karen V; Budni, Josiane; Resende, Wilson R; Varela, Roger B; de Freitas, Karolina V; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2013-12-01

    There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.

  11. Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine

    Directory of Open Access Journals (Sweden)

    Hong-Ju Yang

    2011-01-01

    Full Text Available Amphetamine (AMP is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice. d-AMP (1.0 mg/kg was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.

  12. /sup 123/I-amphetamine-SPECT in the diagnosis of neurological disorders

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    Biersack, H.J.; Kreiten, K.; Hartmann, A.; Friedrich, G.; Linck, H.A.; Winkler, C.

    1985-03-01

    In contrast to conventional brain scintigraphy with sup(99m)Tc-pertechnetate, SPECT with /sup 123/I-IMP enables visualization of the brain tissue itself. The relevance of this imaging technique was evaluated in 54 patients with cerebral disorders. SPECT of the brain was performed with a rotating gamma camera. In 6 of 24 epileptic patients, SPECT revealed foci consistent with EEG-findings which were, however, not detected by CCT. In 4 of 25 patients with cerebrovascular disease, hypoperfused areas were detected by SPECT despite negative results obtained with CCT. In 50% (10/20) of the patients with cerebrovascular disease, SPECT showed a greater functional extent of the lesions than CCT. In 3 patients with migraine and normal CCT, regional perfusion disturbancers were found. SPECT with /sup 123/I-labeled amphetamines, therefore, enables diagnosis of functional perfusion disorders and metabolic disturbances that are not revealed by CCT. In addition, SPECT can be used to exactly demonstrate the functional extent of lesions detected by CCT.

  13. Advances and challenges in pharmacotherapeutics for amphetamine-type stimulants addiction.

    Science.gov (United States)

    Cao, Dan-Ni; Shi, Jing-Jing; Hao, Wei; Wu, Ning; Li, Jin

    2016-06-01

    Addiction to amphetamine-type stimulants (ATS) is a serious worldwide public health problem with major medical, psychiatric and socioeconomic consequences. However, no approved pharmacological therapies are available to treat ATS addiction. Based on the neurobiological mechanisms underlying ATS addiction, the recent research works about pharmacological strategies have been focused on monoamine, glutamate, endogenous opioid peptide and γ-amino butyric acid (GABA) systems. This review summarizes the recent advances in the medications being developed to treat ATS addiction and discusses the remaining challenges. Although no substantial evidence for efficacious medications has emerged, some of these agents, including bupropion, naltrexone and mirtazapine, have demonstrated promise in clinical studies. Moreover, some challenges, such as the development of new preclinical animal models of drug addiction, the design of large-scale clinical trials with strict quality control, and the distinction of patients' genetic polymorphisms, need further attention. Despite the lack of success to date, much effort is being made to develop efficacious medications for treating ATS addiction.

  14. Amphetamine sensitization and amygdala kindling: pharmacological evaluation of catecholaminergic and cholinergic mechanisms.

    Science.gov (United States)

    Kirkby, R D; Kokkinidis, L

    1991-03-01

    Chronic pharmacological experiments were conducted to evaluate the relationship between sensitization induced by repeated administration of amphetamine (AMPH) and electrical stimulation of the amygdala. While AMPH withdrawal did not influence the kindling process, AMPH administered during the kindling procedure increased the rate at which seizures evolved, and under these conditions withdrawal from chronic AMPH further facilitated the propensity to kindle. Haloperidol (HAL) treatment failed to block the stimulant-induced increase in kindling acquisition indicating that changes in dopamine (DA) are not necessary for the AMPH/kindling synergism to develop. Scopolamine dose-dependently retarded kindling evolution irrespective of prior AMPH pretreatment also ruling out a cholinergic mechanism in the kindling sensitization. Subsequent experiments assessed the interactive effects of AMPH and desipramine (DMI) on the kindling process. Animals chronically exposed to AMPH and switched to DMI treatment during the kindling procedure kindled faster than control subjects. In addition, withdrawal from DMI preexposure advanced the AMPH-induced increase in kindling rate. These results were discussed in terms of the role of norepinephrine-mediated inhibition of the kindling process, and were related to drug-elicited alterations in beta-adrenergic receptor functioning. Taken together, these findings implicate the amygdala as an important structure in the development of non-DA forms of AMPH sensitization.

  15. Analysis of amphetamines and metabolites in urine with ultra performance liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ramírez Fernández, María del Mar; Wille, Sarah M R; di Fazio, Vincent; Gosselin, Matthias; Samyn, Nele

    2010-06-01

    A simple, rapid and sensitive ultra performance liquid chromatography tandem mass spectrometry method was developed and fully validated for the quantitative determination of seven amphetamines and metabolites in urine. The method was validated for selectivity, linearity, LOQ, LOD, imprecision, bias, analyte and processed sample stability, matrix effect, recovery, carryover and dilution integrity. A classic liquid-liquid extraction with ethyl acetate was used as sample preparation procedure. The compounds were separated on an Acquity UPLC HSS C18 column in 6.8 min. The linear dynamic range was established from 25 to 500 ng/mL. The limit of quantification was fixed to the lowest calibrator level and the limit of detection ranged from 0.125 to 2.5 ng/mL. The method presented an excellent intra- and inter-assay imprecision and bias (70%) were obtained for all the compounds. No carryover was observed after the analysis of high concentrated samples (8000 ng/mL). The method was subsequently applied to authentic samples.

  16. Headspace liquid-phase microextraction of methamphetamine and amphetamine in urine by an aqueous drop

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    He Yi [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States)]. E-mail: yhe@jjay.cuny.edu; Vargas, Angelica [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States); Kang, Youn-Jung [Department of Sciences, John Jay College of Criminal Justice, City University of New York, 445 W 59th Street, New York, NY 10019 (United States)

    2007-04-25

    This study developed a headspace liquid-phase microextraction (LPME) method by using a single aqueous drop in combination with high performance liquid chromatography (HPLC)-UV detection for the determination of methamphetamine (MAP) and amphetamine (AP) in urine samples. The analytes, volatile and basic, were released from sample matrix into the headspace first, and then protonated and dissolved in an aqueous H{sub 3}PO{sub 4} drop hanging in the headspace by a HPLC syringe. After extraction, this drop was directly injected into HPLC. Parameters affecting extraction efficiency were investigated and optimized. This method showed good linearity in the investigated concentration range of 1.0-1500 {mu}g L{sup -1}, repeatability of the extraction (R.S.D. < 5%, n = 6), and low detection limits (0.3 {mu}g L{sup -1} for both analytes). Enrichment factors of about 400-fold and 220-fold were achieved for MAP and AP, respectively, at optimum conditions. The feasibility of the method was demonstrated by analyzing human urine samples.

  17. Identification and location of the cocaine and amphetamine regulated transcript (CART) in the abomasum of cattle.

    Science.gov (United States)

    Janiuk, Izabela; Młynek, Krzysztof; Wysocki, Jarosław

    2013-05-01

    The cocaine and amphetamine regulated transcript (CART) belongs to the group of peptides with anorexigenic properties and is present in many areas of the central and peripheral nervous systems of numerous mammalian species. Research has suggested an effect on the feeling of appetite and satiety; however, there are no clear clues as to the role of CART in specific organs, including the stomach. Considering the specificity of cattle feeding and digestion, CART may play a highly significant role possibly associated with the option of administering greater amounts of high-volume feeds. Based on the results of immunohistochemical staining of abomasum samples prepared from hybrid bulls, the presence of CART-positive structures and CART distribution were determined in the mucosa, submucosa and muscularis layers of the stomach. Abundant sites of CART were found in the myenteric plexus, nerve fibers innervating the myocytes of the myenteron, neuroendocrine cells of the diffuse neuroendocrine system and the submucous plexus. The preliminary stage of abomasal CART detection suggests that CART is an agent that strongly affects the regulation of motor activity involved in stomach emptying and in secretory functions of the stomach. However, further research is necessary to explain the relationship.

  18. Reduced ethanol consumption and preference in cocaine- and amphetamine-regulated transcript (CART) knockout mice.

    Science.gov (United States)

    Salinas, Armando G; Nguyen, Chinh T Q; Ahmadi-Tehrani, Dara; Morrisett, Richard A

    2014-03-01

    Cocaine- and amphetamine-regulated transcript (CART) is a neuropeptide implicated in addiction to drugs of abuse. Several studies have characterized the role of CART in addiction to psychostimulants, but few have examined the role of CART in alcohol use disorders including alcoholism. The current study utilized a CART knockout (KO) mouse model to investigate the role of CART in ethanol appetitive behaviors. A two-bottle choice, unlimited-access paradigm was used to compare ethanol appetitive behaviors between CART wild type (WT) and KO mice. The mice were presented with an ethanol solution (3%-21%) and water, each concentration for 4 days, and their consumption was measured daily. Consumption of quinine (bitter) and saccharin (sweet) solutions was measured following the ethanol preference tests. In addition, ethanol metabolism rates and ethanol sensitivity were compared between genotypes. CART KO mice consumed and preferred ethanol less than their WT counterparts in both sexes. This genotype effect could not be attributed to differences in bitter or sweet taste perception or ethanol metabolism rates. There was also no difference in ethanol sensitivity in male mice; however, CART KO female mice showed a greater ethanol sensitivity than the WT females. Taken together, these data demonstrate a role for CART in ethanol appetitive behaviors and as a possible therapeutic drug target for alcoholism and abstinence enhancement.

  19. Cocaine- and amphetamine-regulated transcript (CART) protects beta cells against glucotoxicity and increases cell proliferation.

    Science.gov (United States)

    Sathanoori, Ramasri; Olde, Björn; Erlinge, David; Göransson, Olga; Wierup, Nils

    2013-02-01

    Cocaine- and amphetamine-regulated transcript (CART) is an islet peptide that promotes glucose-stimulated insulin secretion in beta cells via cAMP/PKA-dependent pathways. In addition, CART is a regulator of neuronal survival. In this study, we examined the effect of exogenous CART 55-102 on beta cell viability and dissected its signaling mechanisms. Evaluation of DNA fragmentation and chromatin condensation revealed that CART 55-102 reduced glucotoxicity-induced apoptosis in both INS-1 (832/13) cells and isolated rat islets. Glucotoxicity in INS-1 (832/13) cells also caused a 50% reduction of endogenous CART protein. We show that CART increased proliferation in INS-1 (832/13) cells, an effect that was blocked by PKA, PKB, and MEK1 inhibitors. In addition, CART induced phosphorylation of CREB, IRS, PKB, FoxO1, p44/42 MAPK, and p90RSK in INS-1 (832/13) cells and isolated rat islets, all key mediators of cell survival and proliferation. Thus, we demonstrate that CART 55-102 protects beta cells against glucotoxicity and promotes proliferation. Taken together our data point to the potential use of CART in therapeutic interventions targeted at enhancing functional beta cell mass and long-term insulin secretion in T2D.

  20. Neuronal Nicotinic Receptors as New Targets for Amphetamine-Induced Oxidative Damage and Neurotoxicity

    Directory of Open Access Journals (Sweden)

    Elena Escubedo

    2011-06-01

    Full Text Available Amphetamine derivatives such as methamphetamine (METH and 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy” are widely abused drugs in a recreational context. This has led to concern because of the evidence that they are neurotoxic in animal models and cognitive impairments have been described in heavy abusers. The main targets of these drugs are plasmalemmal and vesicular monoamine transporters, leading to reverse transport and increased monoamine efflux to the synapse. As far as neurotoxicity is concerned, increased reactive oxygen species (ROS production seems to be one of the main causes. Recent research has demonstrated that blockade of a7 nicotinic acetylcholine receptors (nAChR inhibits METH- and MDMA-induced ROS production in striatal synaptosomes which is dependent on calcium and on NO-synthase activation. Moreover, a7 nAChR antagonists (methyllycaconitine and memantine attenuated in vivo the neurotoxicity induced by METH and MDMA, and memantine prevented the cognitive impairment induced by these drugs. Radioligand binding experiments demonstrated that both drugs have affinity to a7 and heteromeric nAChR, with MDMA showing lower Ki values, while fluorescence calcium experiments indicated that MDMA behaves as a partial agonist on a7 and as an antagonist on heteromeric nAChR. Sustained Ca increase led to calpain and caspase-3 activation. In addition, modulatory effects of MDMA on a7 and heteromeric nAChR populations have been found.

  1. Discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) in humans trained to discriminate among d-amphetamine, meta-chlorophenylpiperazine and placebo.

    Science.gov (United States)

    Johanson, Chris-Ellyn; Kilbey, Marlyne; Gatchalian, Kristin; Tancer, Manuel

    2006-01-04

    In animals, two-choice drug discrimination studies have demonstrated that the behavioral effects of 3,4-methylenedioxymethamphetamine (MDMA) are mediated by dopaminergic and serotonergic systems. In order to delineate the relative role of these systems, three-choice paradigms have been used in animals, with findings indicating a more prominent role for serotonin. Human studies assessing the subjective and physiological effects of MDMA have also indicated a mixed action. To parallel animal studies, the participants in the present study were trained to discriminate among a prototypic dopaminergic agonist, d-amphetamine, a prototypic serotonergic agonist, meta-chlorophenylpiperazine (mCPP) and placebo and then were tested with two doses of MDMA. In addition, subjective and physiological effects were measured. The results demonstrated that humans could be trained to discriminate among 20 mg d-amphetamine, 0.75 mg/kg mCPP and placebo. When tested with 1.0 and 1.5 mg/kg, half the participants reported MDMA to be like amphetamine and half like mCPP. There were no clear differences between these two groups in other dimensions, although there was an indication that the individuals who discriminated MDMA as d-amphetamine were more sensitive to the effects of all the drugs. The subjective effects of all three drugs overlapped, although the effects of MDMA appeared more amphetamine-like.

  2. [Determination of amphetamines in human hair using dynamic liquid-phase microextraction and gas chromatography/selected ion monitoring-mass spectrometry after microwave derivatization].

    Science.gov (United States)

    Zhu, Dan; Meng, Pinjia; He, Hongyuan

    2007-01-01

    Human hair is an important specimen for drug abuse analysis owing to its easy collection, long surveillance time window and good correlation between the "degree of addiction" and actual drug concentration. A simple method for determination of 4 amphetamines in human hair was developed. The hair was digested under basic condition, and the drugs in it were extracted using microvolume of chloroform. The organic layer was then transferred into another tube to be derivatized with N-methyl-bis (trifluoroacetamide) (MBTFA) by microwave heating. Finally the reacted solution was detected by gas chromatography/selected ion monitoring-mass spectrometry (GC/SIM-MS) directly. 2-Methyl-phenyl ethylamine was used as an internal standard. Good linearities were obtained for 4 amphetamines with correlation coefficients better than 0.996. The limits of detection, based on a signal-to-noise ratio (S/N) of 3:1, were all about 50 pg/mg for amphetamine (AM) , methamphetamine (MAM), methylenedioxy-amphetamine (MDA), and methylenedioxy-methamphetamine (MDMA) in hair. The reproducibility of the method was satisfactory, with the relative standard deviations of 6.0% for AM, 13.9% for MAM, 10.2% for MDA and 9.2% for MDMA. Some real hair from the drug abusers was analyzed with this method. The minimal hair is less than 5 mg (about 20 cm). The method is highly sensitive, easy to operate, time-saving and economic, which can be used for trace analysis of amphetamines in human hair.

  3. Rapid extraction and determination of amphetamines in human urine samples using dispersive liquid-liquid microextraction and solidification of floating organic drop followed by high performance liquid chromatography.

    Science.gov (United States)

    Ahmadi-Jouibari, Toraj; Fattahi, Nazir; Shamsipur, Mojtaba

    2014-06-01

    A novel, rapid, simple and sensitive dispersive liquid-liquid microextraction method based on the solidification of floating organic drop (DLLME-SFO) combined with high-performance liquid chromatography-ultraviolet detection (HPLC-UV) was used to determine amphetamine and methamphetamine in urine samples. The factors affecting the extraction efficiency of DLLME-SFO such as the kind and volume of the extraction and the disperser solvents, effect of concentration of K2CO3 and extraction time were investigated and the optimal extraction conditions were established. Under the optimum conditions (extraction solvent: 30.0μl 1-undecanol; disperser solvent: 300μl acetonitrile; buffer concentration: 2% (w/v) K2CO3 and extraction time: 1min), calibration curves are linear in the range of 10-3000μgl(-1) and limit of detections (LODs) are in the range of 2-8μgl(-1). The relative standard deviations (RSDs) for 100μgl(-1) of amphetamine and methamphetamine in diluted urine are in the range of 6.2-7.8% (n=7). The method was successfully applied for the determination of amphetamine and methamphetamine in the actual urine samples. The relative recoveries of urine samples spiked with amphetamine and methamphetamine are 87.8-113.2%. The obtained results show that DLLME-SFO combined with HPLC-UV is a fast and simple method for the determination of amphetamine and methamphetamine in urine.

  4. False-positive amphetamine/ecstasy (MDMA/3,4-methylenedioxymethamphetamine) (CEDIA) and ecstasy (MDMA/3,4-methylenedioxymethamphetamine) (DRI) test results with fenofibrate.

    Science.gov (United States)

    Kaplan, Yusuf Cem; Erol, Almla; Karadaş, Barş

    2012-10-01

    This case report describes a false-positive amphetamine/ecstasy [3,4-methylenedioxymethamphetamine (MDMA)] and ecstasy (MDMA) screen after therapeutic use of antihyperlipidemic drug, fenofibrate. A 60-year-old male patient was admitted to inpatient psychiatry unit with the diagnosis of alcohol dependency. He was prescribed diazepam 30 mg/day, thiamine 300 mg/day, and naltrexone 50 mg/day. He had also been using fenofibrate 267 mg/day for 3 years for hyperlipidemia and trazodone 100 mg/day for 5 months for insomnia. On routine, urine drugs-of-abuse screening amphetamine/MDMA (CEDIA) test was positive for 4 different occasions and MDMA (DRI) test was positive on 5 different occasions. Gas chromatography/mass spectrometry confirmation of the first positive 3 samples were negative for amphetamine and MDMA. After discontinuation of fenofibrate, amphetamine/MDMA, and MDMA immunoassay results turned out to be negative. Caution should be given to interpretation of amphetamine/MDMA (CEDIA) and MDMA (DRI) tests in patients taking fenofibrate. Specific confirmation with a suitable method should be used to prevent erroneous interpretations.

  5. Molecularly imprinted solid-phase extraction for the selective determination of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs in human whole blood by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Kumazawa, Takeshi; Hasegawa, Chika; Hara, Kenji; Uchigasaki, Seisaku; Lee, Xiao-Pen; Seno, Hiroshi; Suzuki, Osamu; Sato, Keizo

    2012-03-01

    A novel method is described for the extraction of methamphetamine, amphetamine, and methylenedioxyphenylalkylamine designer drugs, such as 3,4-methylenedioxy-methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine, and 3,4-(methylenedioxyphenyl)-2-butanamine, from human whole blood using molecularly imprinted solid-phase extraction as highly selective sample clean-up technique. Whole blood samples were diluted with 10 mmol/L ammonium acetate (pH 8.6) and applied to a SupelMIP-Amphetamine molecularly imprinted solid-phase extraction cartridge. The cartridge was then washed to eliminate interferences, and the amphetamines of interest were eluted with formic acid/methanol (1:100, v/v). After derivatization with trifluoroacetic anhydride, the analytes were quantified using gas chromatography-mass spectrometry. Recoveries of the seven amphetamines spiked into whole blood were 89.1-102%. The limits of quantification for each compound in 200 μL of whole blood were between 0.25 and 1.0 ng. The maximum intra- and inter-day coefficients of variation were 9.96 and 13.8%, respectively. The results show that methamphetamine, amphetamine, and methylenedioxyphenylalkyl-amine designer drugs can be efficiently extracted from crude biological samples such as whole blood by molecularly imprinted solid-phase extraction with good reproducibility. This extraction method will be useful for the pretreatment of human samples before gas chromatography-mass spectrometry.

  6. An unusual presentation of a customs importation seizure containing amphetamine, possibly synthesized by the APAAN-P2P-Leuckart route.

    Science.gov (United States)

    Power, John D; Barry, Michael G; Scott, Kenneth R; Kavanagh, Pierce V

    2014-01-01

    During the analysis of an Irish customs seizure (14 packages each containing approximately one kilogram of a white wet paste) were analysed for the suspected presence of controlled drugs. The samples were found to contain amphetamine and also characteristic by-products including benzyl cyanide, phenylacetone (P2P), methyl-phenyl-pyrimidines, N-formylamphetamine, naphthalene derivatives and amphetamine dimers. The analytical results corresponded with the impurity profile observed and recently reported for the synthesis of 4-methylamphetamine from 4-methylphenylacetoacetonitrile [1]. The synthesis of amphetamine from alpha-phenylacetoacetonitrile (APAAN) was performed (via an acid hydrolysis and subsequent Leuckart reaction) and the impurity profile of the product obtained was compared to those observed in the customs seizure. Observations are made regarding the route specificity of these by-products.

  7. [Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part II. Cases of complex fatal poisonings: interactions of heroine - cocaine - amphetamines].

    Science.gov (United States)

    Rojek, Sebastian; Kłys, Małgorzata; Rzepecka-Woźniak, Ewa; Konopka, Tomasz

    2010-01-01

    The study represents an attempt at employing segmental hair analysis in complex poisonings with xenobiotic mixtures of heroine - cocaine - amphetamines in the context of the cause of death as a consequence of complex interaction mechanisms which occurred prior to death. Two cases of complex poisonings: heroine - cocaine and heroine - cocaine - amphetamines were analyzed and documented with macro- and microscopic examinations and complex toxicological examinations, including the analysis of classic biological material, i.e. samples of selective blood, and alternative material, i.e. hair samples. Determinations of opioids, cocaine and its metabolite and amphetamines in the hair biological matrix were performed using high performance liquid chromatography--atmospheric pressure chemical ionization--tandem mass spectrometry (HPLC-APCI-MS-MS). Segmental hair analysis of the investigated cases indicated a prolonged intake of similar psychoactive substances and a developed adaptation of the addicted to interaction mechanisms, which, however, led gradually to multiorgan anatomopathological changes, and in consequence to death.

  8. Transcriptome profiling of khat (Catha edulis and Ephedra sinica reveals gene candidates potentially involved in amphetamine-type alkaloid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Ryan A Groves

    Full Text Available Amphetamine analogues are produced by plants in the genus Ephedra and by khat (Catha edulis, and include the widely used decongestants and appetite suppressants (1S,2S-pseudoephedrine and (1R,2S-ephedrine. The production of these metabolites, which derive from L-phenylalanine, involves a multi-step pathway partially mapped out at the biochemical level using knowledge of benzoic acid metabolism established in other plants, and direct evidence using khat and Ephedra species as model systems. Despite the commercial importance of amphetamine-type alkaloids, only a single step in their biosynthesis has been elucidated at the molecular level. We have employed Illumina next-generation sequencing technology, paired with Trinity and Velvet-Oases assembly platforms, to establish data-mining frameworks for Ephedra sinica and khat plants. Sequence libraries representing a combined 200,000 unigenes were subjected to an annotation pipeline involving direct searches against public databases. Annotations included the assignment of Gene Ontology (GO terms used to allocate unigenes to functional categories. As part of our functional genomics program aimed at novel gene discovery, the databases were mined for enzyme candidates putatively involved in alkaloid biosynthesis. Queries used for mining included enzymes with established roles in benzoic acid metabolism, as well as enzymes catalyzing reactions similar to those predicted for amphetamine alkaloid metabolism. Gene candidates were evaluated based on phylogenetic relationships, FPKM-based expression data, and mechanistic considerations. Establishment of expansive sequence resources is a critical step toward pathway characterization, a goal with both academic and industrial implications.

  9. Automated identification of novel amphetamines using a pure neural network and neural networks coupled with principal component analysis

    Science.gov (United States)

    Gosav, S.; Praisler, M.; Dorohoi, D. O.; Popa, G.

    2005-06-01

    A pure neural network (NN) and several neural networks coupled with principal component analysis (PC-NN) have been developed in order to identify illicit amphetamines necessary in the investigation of drugs of abuse for epidemiological, clinical, and forensic purposes. The NN system has as input variables 260 spectral data, representing absorption intensities measured for each normalized infrared spectrum at 260 wavenumbers 10 cm -1 apart. In the case of PC-NN systems, the original spectral data (absorption intensities) have been compressed with the principal component analysis method (PCA), the scores of the principal components (PCs) being the inputs of these systems. We have built nine PC-NN systems, which have a different number of input variables: 3PCs, 4PCs, 5PCs, 6PCs, 7PCs, 8PCs, 9PCs, 10PCs and 15PCs. All systems are specialized to distinguish between stimulant amphetamines (class code M), hallucinogenic amphetamines (class code T) and nonamphetamines (class code N). We are now presenting a comparison of the validation results obtained for the NN system and for the best PC-NN system based on the scores of the first nine PCs (9PC-NN). The NN system correctly classifies all the positive samples, as opposed to the 9PC-NN system, which is characterized by a true positive rate (TP) of 90.91%. The true negative rate (TN) obtained for the first system (83.33%) is slightly higher than in the case of the later system (82.71%). Thus, the NN system is more sensitive and selective than the 9PC-NN system. We are also presenting a spectroscopic analysis of the false negative samples obtained in the case of 9PC-NN system.

  10. Amphetamine, cocaine and cannabinoids use among truck drivers on the roads in the State of Sao Paulo, Brazil.

    Science.gov (United States)

    Leyton, V; Sinagawa, D M; Oliveira, K C B G; Schmitz, W; Andreuccetti, G; De Martinis, B S; Yonamine, M; Munoz, D R

    2012-02-10

    Drugs are important risk factors for traffic accidents. In Brazil, truck drivers report using amphetamines to maintain their extensive work schedule and stay awake. These drugs can be obtained without prescription easily on Brazilian roads. The use of these stimulants can result in health problems and can be associated with traffic accidents. There are Brazilian studies that show that drivers use drugs. However, these studies are questionnaire-based and do not always reflect real-life situations. The purpose of this study was to demonstrate the prevalence of drug use by truck drivers on the roads of Sao Paulo State, Brazil, during 2009. Drivers of large trucks were randomly stopped by police officers on the interstate roads during morning hours. After being informed of the goals of the study, the drivers gave written informed consent before providing a urine sample. In addition, a questionnaire concerning sociodemographic characteristics and health information was administered. Urine samples were screened for amphetamines, cocaine, and cannabinoids by immunoassay and the confirmation was performed using gas chromatography-mass spectrometry (GC-MS). Of the 488 drivers stopped, 456 (93.4%) provided urine samples, and 9.3% of them (n=42) tested positive for drugs. Amphetamines were the most commonly found (n=26) drug, representing 61.9% of the positive samples. Ten cases tested positive for cocaine (23.8%), and five for cannabinoids (11.9%). All drivers were male with a mean age of 40 ± 10.8 years, and 29.3% of them reported some health problem (diabetes, high blood pressure and/or stress). A high incidence of truck drivers who tested positive for drug use was found, among other reported health problems. Thus, there is an evident need to promote a healthier lifestyle among professional drivers and a need for preventive measures aimed at controlling the use of drugs by truck drivers in Brazil.

  11. Effects of amphetamine on conditioned place preference and locomotion in the male green tree frog, Hyla cinerea.

    Science.gov (United States)

    Presley, Gina M; Lonergan, William; Chu, Joanne

    2010-01-01

    Neural systems mediating motivation and reward have been well described in mammalian model systems, especially with reference to reward properties of drugs of abuse. Far less is known of the neural mechanisms underlying motivation and reward in non-mammals. The behavioral procedure conditioned place preference (CPP) is often used to quantify reward properties of psychoactive drugs. The indirect dopamine agonist d-amphetamine (AMPH) is known for its properties for inducing CPP in mammals and for inducing dose-related stereotypic movements. We used the green tree frog, Hyla cinerea, to examine whether AMPH could induce both CPP and a dose response change in motor behaviors. We demonstrated that H. cinerea can show place conditioning to AMPH following 14 days of training and that AMPH can cause reversal of a strong baseline place preference. Amphetamine-treated animals (20 mg/kg b.w.) received the drug paired with the previously non-preferred context, and vehicle paired with the preferred context. Control animals received vehicle in both preferred and non-preferred contexts. Amphetamine-treated animals switched context preference following conditioning, whereas control animals did not. We also demonstrated in an open-field experiment that AMPH did not cause any noticeable changes in motor movement or behaviors across a range of doses (0, 10, 20 mg/kg b.w.). This study represents the first examination of the behavioral effects of AMPH in amphibians. These results may contribute to a better understanding of the function and pharmacology of a reward system that may mediate natural behaviors in frogs and other vertebrates.

  12. Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Daniele Z., E-mail: daniele.dzs@dpf.gov.br [Setor Tecnico-Cientifico, Superintendencia Regional do Departamento de Policia Federal no Rio Grande do Sul, 1365 Ipiranga Avenue, Azenha, Zip Code 90160-093 Porto Alegre, Rio Grande do Sul (Brazil); Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Pechansky, Flavio [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Duarte, Paulina C.A.V. [Secretaria Nacional de Politicas sobre Drogas (SENAD), Esplanada dos Ministerios, Block ' A' , 5th floor, Zip Code 70050-907 Brasilia, Distrito Federal (Brazil); De Boni, Raquel [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Froehlich, Pedro E.; Limberger, Renata P. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil)

    2011-06-24

    Graphical abstract: Highlights: > Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. > Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. > Linear range 2(4)-256 ng mL{sup -1}, detection limits 0.5-2 ng mL{sup -1}. > Accuracy 98-112%, precision <15% of RSD, recovery 77-112%. > Importance of residual evaluation in checking model goodness-of-fit. - Abstract: A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal{sup TM} device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL{sup -1} (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL{sup -1}. The detection limits were 0.5 ng mL{sup -1} (MET), 1 ng mL{sup -1} (MPH) and 2 ng mL{sup -1} (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal{sup TM} device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

  13. Insights into the modulation of dopamine transporter function by amphetamine, orphenadrine and cocaine binding

    Directory of Open Access Journals (Sweden)

    Mary Hongying Cheng

    2015-06-01

    Full Text Available Human dopamine transporter (hDAT regulates dopaminergic signaling in the central nervous system by maintaining the synaptic concentration of dopamine (DA at physiological levels, upon reuptake of DA into presynaptic terminals. DA translocation involves the co-transport of two sodium ions and the channeling of a chloride ion, and it is achieved via alternating access between outward-facing and inward-facing states of DAT. hDAT is a target for addictive drugs such as cocaine, amphetamine (AMPH and therapeutic antidepressants. Our recent quantitative systems pharmacology study suggested that orphenadrine (ORPH, an anticholinergic agent and anti-PD drug, might be repurposable as a DAT drug. Previous studies have shown that DAT-substrates like AMPH or -blockers like cocaine modulate the function of DAT in different ways. However, the molecular mechanisms of modulation remained elusive due to the lack of structural data on DAT. The newly resolved DAT structure from Drosophila melanogaster opens the way to a deeper understanding of the mechanism and time evolution of DAT-drug/ligand interactions. Using a combination of homology modeling, docking analysis, molecular dynamics simulations and molecular biology experiments, we performed a comparative study of the binding properties of DA, AMPH, ORPH and cocaine, and their modulation of hDAT function. Simulations demonstrate that binding DA or AMPH drives a structural transition towards a functional form predisposed to translocate the ligand. In contrast, ORPH appears to inhibit DAT function by arresting it in the outward-facing open conformation. The analysis shows that cocaine and ORPH competitively bind DAT, with the binding pose and affinity dependent on the conformational state of DAT. Further assays show that the effect of ORPH on DAT uptake and endocytosis is comparable to that of cocaine.

  14. Simultaneous quantitation of amphetamines and opiates in human hair by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Liu, Ray H; Lin, Dong-Liang

    2015-04-01

    In this study, an incubation, solid-phase extraction (SPE) and LC-MS-MS procedure was developed, validated and used for simultaneous analysis of amphetamine (AP), methamphetamine (MA), morphine (MOR), codeine (COD), 6-acetylmorphine (6-AM) and 6-acetylcodeine (6-AC) in hair. Hair samples were initially cut into sections, washed with dichloromethane, then sonicated in a methanol-trifluoroacetic acid mixture. The resulting solutions were processed with a SPE procedure before undergoing LC-MS-MS analysis. Mass spectrometric analysis was performed in positive-ion, multiple reactions monitoring (MRM) mode, using appropriate collision energy for each selected precursor ion. The overall protocol, when applied to the analysis of hair (50 mg) samples fortified with 100-10,000 pg/mg of the analytes, was found to achieve 55.5-74.6% recovery of the six analytes with the following analytical parameters: (i) intra- and interday precision/accuracy data for the six analytes in the 1.6-7.6%/-6.0-12.8% and 1.3-6.6%/-6.9-9.3% ranges, respectively; (ii) r(2) > 0.998 for all six analytes and (iii) LOD 2 pg/mg for AP and MA, and 8 pg/mg for MOR, COD, 6-AM and 6-AC; LOQ 10 pg/mg for all six analytes. This method was then utilized to (i) analyze hair samples collected from 86 self-reported drug users and (ii) evaluate the deposition pattern of drugs in head hairs from four female MA and heroin users in a rehabilitation facility. This relatively simple protocol was found superior over the GC-MS methods we have previously developed and utilized in our laboratory for the analysis of these six analytes.

  15. Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism.

    Science.gov (United States)

    Moy, Sheryl S; Riddick, Natallia V; Nikolova, Viktoriya D; Teng, Brian L; Agster, Kara L; Nonneman, Randal J; Young, Nancy B; Baker, Lorinda K; Nadler, Jessica J; Bodfish, James W

    2014-02-01

    Restricted repetitive behaviors are core symptoms of autism spectrum disorders (ASDs). The range of symptoms encompassed by the repetitive behavior domain includes lower-order stereotypy and self-injury, and higher-order indices of circumscribed interests and cognitive rigidity. Heterogeneity in clinical ASD profiles suggests that specific manifestations of repetitive behavior reflect differential neuropathology. The present studies utilized a set of phenotyping tasks to determine a repetitive behavior profile for the C58/J mouse strain, a model of ASD core symptoms. In an observational screen, C58/J demonstrated overt motor stereotypy, but not over-grooming, a commonly-used measure for mouse repetitive behavior. Amphetamine did not exacerbate motor stereotypy, but had enhanced stimulant effects on locomotion and rearing in C58/J, compared to C57BL/6J. Both C58/J and Grin1 knockdown mice, another model of ASD-like behavior, had marked deficits in marble-burying. In a nose poke task for higher-order repetitive behavior, C58/J had reduced holeboard exploration and preference for non-social, versus social, olfactory stimuli, but did not demonstrate cognitive rigidity following familiarization to an appetitive stimulus. Analysis of available high-density genotype data indicated specific regions of divergence between C58/J and two highly-sociable strains with common genetic lineage. Strain genome comparisons identified autism candidate genes, including Cntnap2 and Slc6a4, located within regions divergent in C58/J. However, Grin1, Nlgn1, Sapap3, and Slitrk5, genes linked to repetitive over-grooming, were not in regions of divergence. These studies suggest that specific repetitive phenotypes can be used to distinguish ASD mouse models, with implications for divergent underlying mechanisms for different repetitive behavior profiles.

  16. Nicotine regulates cocaine-amphetamine-Regulated Transcript (Cart) in the mesocorticolimbic system.

    Science.gov (United States)

    Kaya, Egemen; Gozen, Oguz; Ugur, Muzeyyen; Koylu, Ersin O; Kanit, Lutfiye; Balkan, Burcu

    2016-07-01

    Cocaine-and-Amphetamine Regulated Transcript (CART) mRNA and peptides are intensely expressed in the brain regions comprising mesocorticolimbic system. Studies suggest that CART peptides may have a role in the regulation of reward circuitry. The present study aimed to examine the effect of nicotine on CART expression in the mesocorticolimbic system. Three different doses of nicotine (0.2, 0.4, 0.6 mg/kg free base) were injected subcutaneously for 5 days, and on day 6, rats were decapitated following a challenge dose. CART mRNA and peptide levels in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), dorsal striatum (DST), amygdala (AMG), lateral hypothalamic area (LHA), and ventral tegmental area (VTA) were measured by quantitative real-time PCR (qPCR) and Western Blot analysis, respectively. In the mPFC, 0.4 and 0.6 mg/kg nicotine, decreased CART peptide levels whereas there was no effect on CART mRNA levels. In the VTA, a down-regulation of CART peptide expression was observed with 0.2 and 0.6 mg/kg nicotine. Conversely, 0.4 and 0.6 mg/kg nicotine increased CART mRNA levels in the AMG without affecting the CART peptide expression. Nicotine did not regulate CART mRNA or CART peptide expression in the NAc, DST, and LHA. We conclude that nicotine regulates CART expression in the mesocorticolimbic system and this regulation may play an important role in nicotine reward. Synapse 70:283-292, 2016. © 2016 Wiley Periodicals, Inc.

  17. Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux.

    Science.gov (United States)

    Binda, Francesca; Dipace, Concetta; Bowton, Erica; Robertson, Sabrina D; Lute, Brandon J; Fog, Jacob U; Zhang, Minjia; Sen, Namita; Colbran, Roger J; Gnegy, Margaret E; Gether, Ulrik; Javitch, Jonathan A; Erreger, Kevin; Galli, Aurelio

    2008-10-01

    The soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein syntaxin 1A (SYN1A) interacts with and regulates the function of transmembrane proteins, including ion channels and neurotransmitter transporters. Here, we define the first 33 amino acids of the N terminus of the dopamine (DA) transporter (DAT) as the site of direct interaction with SYN1A. Amphetamine (AMPH) increases the association of SYN1A with human DAT (hDAT) in a heterologous expression system (hDAT cells) and with native DAT in murine striatal synaptosomes. Immunoprecipitation of DAT from the biotinylated fraction shows that the AMPH-induced increase in DAT/SYN1A association occurs at the plasma membrane. In a superfusion assay of DA efflux, cells overexpressing SYN1A exhibited significantly greater AMPH-induced DA release with respect to control cells. By combining the patch-clamp technique with amperometry, we measured DA release under voltage clamp. At -60 mV, a physiological resting potential, AMPH did not induce DA efflux in hDAT cells and DA neurons. In contrast, perfusion of exogenous SYN1A (3 microM) into the cell with the whole-cell pipette enabled AMPH-induced DA efflux at -60 mV in both hDAT cells and DA neurons. It has been shown recently that Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated by AMPH and regulates AMPH-induced DA efflux. Here, we show that AMPH-induced association between DAT and SYN1A requires CaMKII activity and that inhibition of CaMKII blocks the ability of exogenous SYN1A to promote DA efflux. These data suggest that AMPH activation of CaMKII supports DAT/SYN1A association, resulting in a mode of DAT capable of DA efflux.

  18. Maternal and fetal cocaine- and amphetamine-regulated transcript in diabetic and non-diabetic pregnancy.

    LENUS (Irish Health Repository)

    Hehir, Mark P

    2012-09-01

    Cocaine- and amphetamine-regulated transcript (CART) is a leptin-regulated anorectic neuropeptide. Increased levels of leptin in cord blood of diabetic mothers have previously been described. The aim of this study was to quantify maternal and fetal serum CART levels in type 1 diabetes mellitus (T1DM, n = 10) and non-diabetic pregnancy (n = 10). Matched maternal serum samples (n = 20) were obtained at 36-weeks gestation and cord samples from the umbilical vein at delivery (n = 20), CART was quantified using a competitive enzyme immunoassay. Statistical analysis was performed using Spearmans correlation and t test. There was no difference in maternal CART levels at 36-weeks gestation between T1DM (mean = 331.13 pg\\/ml, Standard Error of the Mean (SEM) = 114.54) and non-diabetic pregnancy (mean = 195.01 pg\\/ml SEM = 29.37) (p = 0.106). Fetal CART levels in the umbilical vein were similar in T1DM (mean = 199.27 pg\\/ml, SEM = 39.81) and non-diabetic pregnancy (mean = 149.76 pg\\/ml, SEM = 26.08) (p = 0.143). Maternal serum CART levels measured at 36-weeks gestation correlated with maternal BMI at booking (Spearmans ρ = 0.332) (p = 0.001) irrespective of diabetes. Serum CART can be detected in both diabetic and non-diabetic human pregnancy and may play an important role in body mass regulation in pregnancy.

  19. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    Energy Technology Data Exchange (ETDEWEB)

    Zaczek, R.; Culp, S.; De Souza, E.B. (Addiction Research Center, Baltimore, MD (USA))

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  20. Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia.

    Science.gov (United States)

    El-Sayed El-Sisi, Alaa; Sokkar, Samia Salem; El-Sayed El-Sayad, Magda; Sayed Ramadan, Ehab; Osman, Enass Yossef

    2016-08-01

    The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib+risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib+risperidone, omega-3+risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib+risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.

  1. The effects of exposure to extremely low-frequency magnetic field and amphetamine on the reduced glutathione in the brain.

    Science.gov (United States)

    Jelenković, Ankica; Janać, Branka; Pesić, Vesna; Jovanović, Marina D; Vasiljević, Ivana; Prolić, Zlatko

    2005-06-01

    Continuous exposure to extremely low-frequency magnetic field (ELF-MF, 50 Hz, 0.5 mT) alone and combined with D-amphetamine (1.5 mg/kg) affected the reduced glutathione content in brain regions of rats. Compared to sham-exposed rats, the glutathione content in the forebrain cortex of the ELF-MF-exposed rats decreased (P glutathione content was increased in the brain stem and cerebellum (P glutathione changes observed. The changes are not uniform in the brain regions examined.

  2. Involvement of oxidative stress in the regulation of NPY/CART-mediated appetite control in amphetamine-treated rats.

    Science.gov (United States)

    Hsieh, Yih-Shou; Chen, Pei-Ni; Yu, Ching-Han; Chen, Chia-Hui; Tsai, Tsung-Ta; Kuo, Dong-Yih

    2015-05-01

    Amphetamine (AMPH) treatment can suppress appetite and increase oxidative stress in the brain. AMPH-induced appetite suppression is associated with the regulation of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus. The present study explored whether antioxidants, including glutathione S-transferase (GST) and glutathione peroxidase (GP), were involved in this NPY/CART-mediated appetite control. Rats were treated daily with AMPH for four days. Changes in food intake and expression levels of hypothalamic NPY, CART, GST, and GP were examined and compared. Results showed that, in AMPH-treated rats, (1) food intake and NPY expression decreased, while CART, GST, and GP expression increased; (2) NPY knockdown in the brain enhanced the decrease in NPY and the increases in CART, GST, and GP expression; and (3) central inhibition of reactive oxygen species production decreased GST and GP and modulated AMPH anorexia and the expression levels of NPY and CART. The present results suggest that oxidative stress in the brain participates in regulating NPY/CART-mediated appetite control in AMPH-treated rats. These results may advance the knowledge regarding the molecular mechanism of AMPH-evoked or NPY/CART-mediated appetite suppression.

  3. The use of a gold electrode for the determination of amphetamine derivatives and application to their analysis in human urine

    Directory of Open Access Journals (Sweden)

    Nevešćanin Marina M.

    2013-01-01

    Full Text Available The catalytic abilities of gold electrode were tested for the quantitative determination of amphetamine (A and 3,4-methylenedioxy-N-methylamphetamine (MDMA standards by their oxidation using cyclic voltammetry (CV. The value of the oxidative currents of A and MDMA standards at 0.80 V vs. SCE in 0.05 M NaHCO3 at the scan rate of 50 mV/s is linear function of concentration in range of 110.9-258.9 mM and 38.7-229.2 mM, respectively. Square wave voltammetry (SWV revealed linear increase of current with concentration of MDMA (range 30.9-91.6 mM and thus quantitative determination of amphetamine derivates. SWV analysis is successfully performed in spiked urine samples as well. A and MDMA in the presence of sucrose and as a content in illegally produced tablets were also analyzed. The voltammetric determination of A and MDMA derivatives using CV and SWV at gold electrode is a rapid, selective and simple procedure and its accuracy was confirmed with reference method, high performance liquid chromatography (HPLC. The spiked urine samples analysis offers additional possibility for the rapid detection of A and MDMA in human urine.

  4. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    Science.gov (United States)

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C

    2007-07-10

    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  5. Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry

    Science.gov (United States)

    Crevelin, Eduardo J.; Salami, Fernanda H.; Alves, Marcela N. R.; De Martinis, Bruno S.; Crotti, Antônio E. M.; Moraes, Luiz A. B.

    2016-05-01

    Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

  6. Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam.

    Science.gov (United States)

    Kelly, T H; Foltin, R W; Emurian, C S; Fischman, M W

    1993-09-01

    The time courses of the effects of acute doses of amphetamine (5 and 10 mg/70 kg), alcohol (0.3 and 0.6 g/kg), diazepam (5 and 10 mg/70 kg), and marijuana (2.0% and 3.5% delta 9-THC) on performance engendered by each of four computerized behavioral tasks were evaluated in six human subjects. These performance-based tasks have potential commercial utility for drug-use detection in the workplace. Alcohol and marijuana effects were reliably detected for up to three hours following dose administration with most procedures. Amphetamine and diazepam effects were also detected, but the dose effects and time courses were variable. The profile of behavioral effects varied across drugs, suggesting that performance-based testing procedures might be useful in discriminating which drug was administered and the time course of the drug's effects. Results indicate that repeated measurement with performance-based drug detection procedures can provide immediate indications of performance impairment in a cost-effective and noninvasive manner and, as such, would be a useful supplement to biological sample testing for drug-use detection.

  7. Sex-specific differences in the dynamics of cocaine- and amphetamine-regulated transcript and nesfatin-1 expressions in the midbrain of depressed suicide victims vs. controls.

    NARCIS (Netherlands)

    Bloem, B.R.; Xu, L.; Morava, E.; Faludi, G.; Palkovits, M.; Roubos, E.W.; Kozicz, T.

    2012-01-01

    An intriguing novel pathophysiological insight into mood disorders is the notion that one's metabolic status influences mood. In rodents, cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1/NUCB2 have not only been implicated in metabolism, but in the pathobiology of anxiety and depr

  8. Amphetamine-type stimulant use among men who have sex with men (MSM) in Vietnam : Results from a socio-ecological, community-based study

    NARCIS (Netherlands)

    Vu, Nga Thi Thu; Holt, Martin; Phan, Huong Thi Thu; Le, Huong Thi; La, Lan Thi; Tran, Gioi Minh; Doan, Tung Thanh; Nguyen, Trang Nhu Nguyen; de Wit, John

    2016-01-01

    INTRODUCTION: Amphetamine-type-stimulants (ATS) use is associated with HIV-related sexual risk behaviours and is an emergent problem among men who have sex with men (MSM) in Vietnam. The purpose of this study is to describe ATS use patterns and understand the correlates of recent methamphetamine use

  9. Cocaine- and amphetamine-regulated transcript is present in hypothalamic neuroendocrine neurones and is released to the hypothalamic-pituitary portal circuit

    DEFF Research Database (Denmark)

    Larsen, P J; Seier, V; Fink-Jensen, A

    2003-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is present in a number of hypothalamic nuclei. Besides actions in circuits regulating feeding behaviour and stress responses, the hypothalamic functions of CART are largely unknown. We report that CART immunoreactivity is present in hypothalamic...

  10. [Application of hair analysis of selected psychoactive substances for medico-legal purposes. Part I. Segmental hair analysis in cases of fatal opioids and amphetamines poisoning].

    Science.gov (United States)

    Rojek, Sebastian; Kłys, Małgorzata; Konopka, Tomasz

    2009-01-01

    The present experimental investigations were inspired by the necessity of standardizing the procedures and analytical methods employed in hair analysis aiming at a retrospective evaluation of ingestion of various xenobiotics. Thus, in keeping with the principal premises, the main objective of the study was development of unique, novel chemico-toxicological procedures for analyzing hair content of psychoactive substances in two basic groups of substances of abuse: opioids (morphine, 6-monoacetylmorphine, codeine) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA) by HPLC-APCI-MS-MS, followed by verification of the thus worked out procedures in medico-legal practice through opinionating in selected group of patients deceased due to fatal psychoactive substance poisoning (cause of death determination). Determinations of opioids and amphetamines in the hair biological matrix were performed using high performance liquid chromatography - atmospheric pressure chemical ionization - tandem mass spectrometry (HPLC-APCI-MS-MS). In the group of fatal poisonings by ,,Polish heroine", hair segmental analysis confirmed the abuse profile of the opiate or mixed (opiate-amphetamine) type, which to some measure is characteristic of Polish drug addiction, indicating the presence of these xenobiotics in the investigating hair samples in the premortem period.

  11. Analysis of the impulsive aggression and decision-making ability in the inpatients with amphetamine-type stimulants-induced psychiatric disorders

    Institute of Scientific and Technical Information of China (English)

    苏中华

    2014-01-01

    Objective To understand the characteristics of impulsive aggression and the ability of decision-making in the inpatients with amphetamine-type stimulants(ATS)-induced psychiatric disorder,and explore their changes before and after treatment with antipsychotic drugs.Methods One hundred inpatients(patient group)who met the diagnostic criterion of ATS-induced psychiatric

  12. Solvent-enhanced microwave-assisted derivatization following solid-phase extraction combined with gas chromatography-mass spectrometry for determination of amphetamines in urine.

    Science.gov (United States)

    Chung, Li-Wen; Liu, Geng-Jhih; Li, Zu-Guang; Chang, Yan-Zin; Lee, Maw-Rong

    2008-10-15

    An approach using microwave-assisted derivatization (MAD) following solid-phase extraction (SPE) combined with gas chromatography-mass spectrometry (GC-MS) was developed to determine amphetamines in urine samples. The parameters affecting the derivatization efficiency - including microwave power and irradiation time - were investigated. Besides, solvent is thought critically important to MAD. Derivatization performance was studied using various solvents and compared with the performance obtained without solvent. Derivatization efficiency was clearly found to be enhanced by the presence of solvent. The highest derivatization efficiencies were obtained in ethyl acetate (EA) under microwave power of 250W for 1min. Calibration curves for all amphetamines were linear over a range from 1 to 1000ng/mL, with correlation coefficients above 0.9992. The intra-day and inter-day precision were less than 15%. The applicability of the method was tested by analyzing amphetamine-abusing subjects urine samples. Accordingly, the solvent-enhanced MAD-GC-MS method appears to be adequate for determining amphetamines in urine.

  13. Prostaglandin H synthase-catalyzed bioactivation of amphetamines to free radical intermediates that cause CNS regional DNA oxidation and nerve terminal degeneration.

    Science.gov (United States)

    Jeng, Winnie; Ramkissoon, Annmarie; Parman, Toufan; Wells, Peter G

    2006-04-01

    Reactive oxygen species (ROS) are implicated in amphetamine-initiated neurodegeneration, but the mechanism is unclear. Here, we show that amphetamines are bioactivated by CNS prostaglandin H synthase (PHS) to free radical intermediates that cause ROS formation and neurodegenerative oxidative DNA damage. In vitro incubations of purified PHS-1 with 3,4-methylenedioxyamphetamine (MDA) and methamphetamine (METH) demonstrated PHS-catalyzed time- and concentration-dependent formation of an amphetamine carbon- and/or nitrogen-centered free radical intermediate, and stereoselective oxidative DNA damage, evidenced by 8-oxo-2'-deoxyguanosine (8-oxo-dG) formation. Similarly in vivo, MDA and METH caused dose- and time-dependent DNA oxidation in multiple brain regions, remarkably dependent on the regional PHS levels, including the striatum and substantia nigra, wherein neurodegeneration of dopaminergic nerve terminals was evidenced by decreased immunohistochemical staining of tyrosine hydroxylase. Motor impairment using the rotarod test was evident within 3 wk after the last drug dose, and persisted for at least 6 months. Pretreatment with the PHS inhibitor acetylsalicylic acid blocked MDA-initiated DNA oxidation and protected against functional motor impairment for at least 1.5 months after drug treatment. This is the first direct evidence for PHS-catalyzed bioactivation of amphetamines causing temporal and regional differences in CNS oxidative DNA damage directly related to structural and functional neurodegenerative consequences.

  14. 苯丙胺类物质依赖的脑弥散张量成像研究%The brain diffusion tensor imaging study on amphetamine addiction

    Institute of Scientific and Technical Information of China (English)

    温金峰; 成丽娜; 宁连才; 张延赤; 汪文胜

    2011-01-01

    Objective To investigate the influence of amphetamines on the structures of human brain white matter. Methods Magnetic resonance diffusion tensor maging (DTI) and reconstruction of the white matter fiber tracts were performed on 11 cases of amphetamines dependence patients and 6 normal controls. The comparisons of DIT results were then made between patients with amphetamine addiction and controls. Results Both the lift- and right-sided corti-cospinal tracts were significantly lower in amphetamines dependence group than in the control group(P 0.05).结论 苯丙胺类物质依赖者大脑双侧皮质脊髓束及左扣带束受损.且左扣带束纤维受损随物质使用时间延长而加重;未见苯丙胺物质依赖者的精神症状与DTI值相关,但需要进一步证实.

  15. Stress-Induced Locomotor Sensitization to Amphetamine in Adult, but not in Adolescent Rats, Is Associated with Increased Expression of ΔFosB in the Nucleus Accumbens

    Science.gov (United States)

    Carneiro de Oliveira, Paulo E.; Leão, Rodrigo M.; Bianchi, Paula C.; Marin, Marcelo T.; Planeta, Cleopatra da Silva; Cruz, Fábio C.

    2016-01-01

    While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively) were restrained for 2 h once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p.) and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both the adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats. PMID:27672362

  16. Genetic variation associated with euphorigenic effects of d-amphetamine is associated with diminished risk for schizophrenia and attention deficit hyperactivity disorder.

    Science.gov (United States)

    Hart, Amy B; Gamazon, Eric R; Engelhardt, Barbara E; Sklar, Pamela; Kähler, Anna K; Hultman, Christina M; Sullivan, Patrick F; Neale, Benjamin M; Faraone, Stephen V; de Wit, Harriet; Cox, Nancy J; Palmer, Abraham A

    2014-04-22

    Here, we extended our findings from a genome-wide association study of the euphoric response to d-amphetamine in healthy human volunteers by identifying enrichment between SNPs associated with response to d-amphetamine and SNPs associated with psychiatric disorders. We found that SNPs nominally associated (P ≤ 0.05 and P ≤ 0.01) with schizophrenia and attention deficit hyperactivity disorder were also nominally associated with d-amphetamine response. Furthermore, we found that the source of this enrichment was an excess of alleles that increased sensitivity to the euphoric effects of d-amphetamine and decreased susceptibility to schizophrenia and attention deficit hyperactivity disorder. In contrast, three negative control phenotypes (height, inflammatory bowel disease, and Parkinson disease) did not show this enrichment. Taken together, our results suggest that alleles identified using an acute challenge with a dopaminergic drug in healthy individuals can be used to identify alleles that confer risk for psychiatric disorders commonly treated with dopaminergic agonists and antagonists. More importantly, our results show the use of the enrichment approach as an alternative to stringent standards for genome-wide significance and suggest a relatively novel approach to the analysis of small cohorts in which intermediate phenotypes have been measured.

  17. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    NARCIS (Netherlands)

    Armbruszt, S.; Abraham, H.; Figler, M.; Kozicz, T.L.; Hajnal, A.

    2013-01-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the

  18. Stress-induced locomotor sensitization to amphetamine in adult, but not in adolescent rats, is associated with increased expression of ΔFosB in the nucleus accumbens.

    Directory of Open Access Journals (Sweden)

    Paulo Eduardo Carneiro de Oliveira

    2016-09-01

    Full Text Available While clinical and pre-clinical evidence suggests that adolescence is a risk period for the development of addiction, the underlying neural mechanisms are largely unknown. Stress during adolescence has a huge influence on drug addiction. However, little is known about the mechanisms related to the interaction among stress, adolescence and addiction. Studies point to ΔFosB as a possible target for this phenomenon. In the present study, adolescent and adult rats (postnatal day 28 and 60, respectively were restrained for 2 hours once a day for 7 days. Three days after their last exposure to stress, the animals were challenged with saline or amphetamine (1.0 mg/kg i.p. and amphetamine-induced locomotion was recorded. Immediately after the behavioral tests, rats were decapitated and the nucleus accumbens was dissected to measure ΔFosB protein levels. We found that repeated restraint stress increased amphetamine-induced locomotion in both adult and adolescent rats. Furthermore, in adult rats, stress-induced locomotor sensitization was associated with increased expression of ΔFosB in the nucleus accumbens. Our data suggest that ΔFosB may be involved in some of the neuronal plasticity changes associated with stress induced-cross sensitization with amphetamine in adult rats.

  19. Reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely hospitalized elderly medical patients

    DEFF Research Database (Denmark)

    Glintborg, B.; Olsen, L.; Poulsen, H.

    2008-01-01

    Undisclosed use of illicit drugs and prescription controlled substances is frequent in some settings. The aim of the present study was to estimate the reliability of self-reported use of amphetamine, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates among acutely...

  20. Risk-assessment and risk-taking behavior predict potassium- and amphetamine-induced dopamine response in the dorsal striatum of rats

    Directory of Open Access Journals (Sweden)

    Sara ePalm

    2014-07-01

    Full Text Available Certain personality types and behavioral traits display high correlations to drug use and an increased level of dopamine in the reward system is a common denominator of all drugs of abuse. Dopamine response to drugs has been suggested to correlate with some of these personality types and to be a key factor influencing the predisposition to addiction. This study investigated if behavioral traits can be related to potassium- and amphetamine-induced dopamine response in the dorsal striatum, an area hypothesized to be involved in the shift from drug use to addiction. The open field and multivariate concentric square field™ tests were used to assess individual behavior in male Wistar rats. Chronoamperometric recordings were then made to study the potassium- and amphetamine-induced dopamine response in vivo. A classification based on risk-taking behavior in the open field was used for further comparisons. Risk-taking behavior was correlated between the behavioral tests and high risk takers displayed a more pronounced response to the dopamine uptake blocking effects of amphetamine. Behavioral parameters from both tests could also predict potassium- and amphetamine-induced dopamine responses showing a correlation between neurochemistry and behavior in risk-assessment and risk-taking parameters. In conclusion, the high risk-taking rats showed a more pronounced reduction of dopamine uptake in the dorsal striatum after amphetamine indicating that this area may contribute to the sensitivity of these animals to psychostimulants and proneness to addiction. Further, inherent dopamine activity was related to risk-assessment behavior, which may be of importance for decision-making and inhibitory control, key components in addiction.

  1. Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells.

    Science.gov (United States)

    Hondebrink, Laura; Meulenbelt, Jan; Rietjens, Saskia J; Meijer, Marieke; Westerink, Remco H S

    2012-03-01

    Reversal of the dopamine (DA) membrane transporter is the main mechanism through which many drugs of abuse increase DA levels. However, drug-induced modulation of exocytotic DA release by electrical (depolarization) and neurochemical inputs (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP) (1-1000 μM) on these inputs by measuring drug-induced changes in basal, depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest drug-induced effects were observed on cholinergic input. At 0.1mM all drugs inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, low concentrations of methamphetamine or amphetamine (10 μM) potentiated ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases were also inhibited following exposure to high drug concentrations, although drugs were less potent on this endpoint. Our data demonstrate that at high drug concentrations all tested drugs reduce stimulation-evoked increases in [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) at high concentrations of MDMA and mCPP likely increases dopaminergic output. Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation following exposure to low concentrations of amphetamines can contribute to drug-induced increases in DA levels observed in vivo. Finally, this study shows that mCPP, which is regularly found in

  2. D-amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model

    DEFF Research Database (Denmark)

    Rasmussen, Rune Skovgaard; Overgaard, K; Hildebrandt-Eriksen, E S

    2006-01-01

    BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats...... were trained in appropriate cognitive and motor behaviours. Thirteen animals were sham-operated and fifty-nine animals were embolized in the right carotid territory. Animals were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2) CONTROL (embolized, saline), 3) D-AMPH (embolized, D...... were allowed to voluntarily engage in suitable cognitive or motor behaviours in order to obtain food. Animals from all groups were re-tested during days 21-28 after surgery. RESULTS: No differences in infarct volumes were observed between the groups of embolized animals. When evaluating performances...

  3. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder: an update.

    Science.gov (United States)

    Awudu, Gariba A H; Besag, Frank M C

    2014-09-01

    Several million children and a growing number of adults are currently being treated for attention-deficit hyperactivity disorder (ADHD) worldwide. Concerns have been expressed about possible cardiac effects of the common treatments, namely methylphenidate, amphetamines and atomoxetine. Small increases in mean heart rate (HR) and mean blood pressure (BP) have been reported for all three drugs, but most of the studies have not yielded statistically significant results. These studies also have limitations, particularly regarding the lack of accepted and standardised measurement methods. Several large studies of the very rare phenomenon of sudden death in children have failed to show any convincing association with ADHD treatment. Whether minor increases in HR and BP have a cumulative effect over many years and have a long-term adverse effect on cardiovascular health remains undetermined.

  4. Rapid simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by GC-MS.

    Science.gov (United States)

    Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki

    2007-01-04

    This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

  5. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

    Science.gov (United States)

    Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

    2012-02-15

    A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs.

  6. Identification of Prenatal Amphetamines Exposure by Maternal Interview and Meconium Toxicology in the Infant Development, Environment and Lifestyle (IDEAL) Study

    Science.gov (United States)

    Gray, Teresa R.; LaGasse, Linda L.; Smith, Lynne M.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia M.; Della Grotta, Sheri A.; Strauss, Arthur; Haning, William F.; Lester, Barry M.; Huestis, Marilyn A.

    2009-01-01

    The Infant Development Environment and Lifestyle (IDEAL) study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Materials and Methods Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry (GCMS). Results The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by GCMS. Tobacco exposure was equally detected by immunoassay cotinine screen and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use, frequency or route of MAMP use. Discussion Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women ceased MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Conclusion Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers. PMID:19935364

  7. Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fritch, Dean; Blum, Kristen; Nonnemacher, Sheena; Haggerty, Brenda J; Sullivan, Matthew P; Cone, Edward J

    2009-01-01

    Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid.

  8. Identification of prenatal amphetamines exposure by maternal interview and meconium toxicology in the Infant Development, Environment and Lifestyle (IDEAL) study.

    Science.gov (United States)

    Gray, Teresa R; LaGasse, Linda L; Smith, Lynne M; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia M; Della Grotta, Sheri A; Strauss, Arthur; Haning, William F; Lester, Barry M; Huestis, Marilyn A

    2009-12-01

    The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by gas chromatography mass spectrometry. Tobacco exposure was equally detected by immunoassay cotinine screening and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use or frequency or route of MAMP use. Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women stopped MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.

  9. Performance deficits of NK1 receptor knockout mice in the 5-choice serial reaction-time task: effects of d-amphetamine, stress and time of day.

    Directory of Open Access Journals (Sweden)

    Ting Carrie Yan

    Full Text Available BACKGROUND: The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/- resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD. Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. METHODS AND RESULTS: The 5-Choice Serial Reaction-Time Task (5-CSRTT was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI and a variable (VITI inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.. NK1R-/- mice expressed greater omissions (inattentiveness, perseveration and premature responses (impulsivity in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. CONCLUSION: In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally

  10. Development of a targeted GC/MS screening method and validation of an HPLC/DAD quantification method for piperazines–amphetamines mixtures in seized material

    Directory of Open Access Journals (Sweden)

    Yacine Boumrah

    2014-09-01

    Full Text Available Piperazine-related drugs are sold as party pills in the form of tablets, capsules, liquids or powders. These party pills can contain several piperazine derivatives, or even a mixture of piperazines and amphetamine derivatives. This paper describes a screening method using a gas chromatography–mass spectrometry technique allowing the separation and the identification of active components within these mixtures by a combined silylation and acylation derivatization procedure. The studied substances–namely: 1-benzylpiperazine (BZP, 1-(3,4-methylenedioxyben-zylpiperazine (MDBP, 1-(3-trifluoromethylphenylpiperazine (TFMPP, 1-(3-chlorophenyl piperazine (mCPP, 1-(4-methoxyphenyl piperazine (MeOPP, amphetamine, methamphetamine, ephedrine, pseudoephedrine, 3,4-methylenedioxy-N-methamphetamine (MDMA, 3,4-methylenedi-oxyamphetamine (MDA, 3,4-methylenedioxy-N-ethylamphetamine (MDEA and N-methyl-1,3-benzodioxolylbutanamine (MBDB–are separated.

  11. Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid phase microextraction coupled to high performance liquid chromatography and analysis of amphetamines in urine samples.

    Science.gov (United States)

    Fan, Yi; Feng, Yu-Qi; Zhang, Jian-Tao; Da, Shi-Lu; Zhang, Min

    2005-05-13

    In-tube solid-phase microextraction (SPME) based on a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column was investigated for the extraction of amphetamine, methamphetamine and their methylenedioxy derivatives. The monolithic capillary column showed high extraction efficiency towards target analytes, which could be attributed to its larger loading amount of extraction phase than conventional open-tubular extraction capillaries and the convective mass transfer procedure provided by its monolithic structure. The extraction mechanism was studied, and the results indicated that the extraction process of the target analytes was involved with hydrophobic interaction and ion-exchange interaction. The polymer monolith in-tube SPME-HPLC system with UV detection was successfully applied to the determination of amphetamine, methamphetamine and their methylenedioxy derivatives in urine samples, yielding the detection limits of 1.4 - 4.0 ng/mL. Excellent method reproducibility (RSD urine samples.

  12. Sensorimotor gating in NTS1 and NTS2 null mice: effects of d-amphetamine, dizocilpine, clozapine and NT69L

    OpenAIRE

    Oliveros, Alfredo; Heckman, Michael G.; del Pilar Corena-McLeod, Maria; Williams, Katrina; Boules, Mona; Richelson, Elliott

    2010-01-01

    Pre-pulse inhibition (PPI) of the acoustic startle reflex is deficient in patients with schizophrenia. This deficiency is mimicked in mice by the use of the psychotomimetic drugs d-amphetamine and dizolcipine. Antipsychotic drugs such as clozapine are used to treat schizophrenic patients and are also administered to mice to prevent PPI disruption. Neurotensin (NT) produces antipsychotic-like effects when injected into rodent brain through its effects at NT subtype 1 (NTS1) and 2 (NTS2) recept...

  13. Use of drugs of abuse in less than 30-year-old drivers killed in a road crash in France: a spectacular increase for cannabis, cocaine and amphetamines.

    Science.gov (United States)

    Mura, P; Chatelain, C; Dumestre, V; Gaulier, J M; Ghysel, M H; Lacroix, C; Kergueris, M F; Lhermitte, M; Moulsma, M; Pépin, G; Vincent, F; Kintz, P

    2006-07-13

    A collaborative study was conducted in France in order to determine the prevalence of cannabinoids, opiates, cocaine metabolites and amphetamines in blood samples from drivers killed in road accidents in 2003 and 2004 and to compare these values with those of a previous study performed during the period 2000-2001 involving 900 drivers. Blood samples were provided from 2003 under 30-year-old drivers, killed in a traffic accident. Drugs of abuse were determined by gas chromatography-mass spectrometry using the same analytical procedures in all the 12 laboratories. The most frequently observed compounds were by far cannabinoids, that tested positive in 39.6% of the total number of samples. Delta9 tetrahydrocannabinol (THC), the most active of the principle constituents in marijuana (cannabis sativa), was detected in the blood of 28.9% drivers and was the single drug of abuse in 80.2% of the positive cases. It was associated with amphetamines in 7.4% and with opiates and cocaine in 1.9 and 4.8%, respectively. Amphetamines were present in 3.1% of the total number of samples, cocaine metabolites in 3.0% and opiates in 3.5%. When comparing these results with those of a previous study performed 3 years before, a significant increase is observed for THC (28.9% versus 16.9%), cocaine metabolites (3.0% versus 0.2%) and amphetamines (3.1% versus 1.4%). This study demonstrates the critical necessity of implementing in France as soon as possible systematical roadside testing for drugs of abuse.

  14. Effects of altering motivation for food in rats trained with food reinforcement to discriminate between d-amphetamine and saline injections.

    Science.gov (United States)

    Lotfizadeh, Amin D; Redner, Ryan; Edwards, Timothy L; Quisenberry, Amanda J; Baker, Lisa E; Poling, Alan

    2012-12-01

    Previous studies have shown that altering motivation typically affects stimulus generalization in animals trained to discriminate exteroceptive stimuli, but few studies have evaluated the effects of manipulating motivation on drug stimuli. In the few published studies, motivation levels were manipulated by arranging different feeding conditions prior to stimulus generalization tests with rats trained to discriminate morphine from vehicle and in pigeons trained to discriminate phencyclidine or pentobarbital from vehicle. In the present study, rats maintained at 80% of free-feeding weights were trained to discriminate between injections of 1.0mg/kg d-amphetamine and saline in a two-lever food-reinforced operant procedure. Generalization tests were then conducted with a range of d-amphetamine doses (0, 0.03, 0.1, and 0.3, 1.0mg/kg) when the rats were not fed before experimental sessions (high motivation) and when they were pre-fed 1g of food (moderate motivation) or their daily ration of food (low motivation) 1h before test sessions. Changing the motivation level significantly affected response rate and latency to the first response in generalizations tests, but did not significantly affect mean percentage of drug-appropriate responding (a continuous measure) or percentage of animals that selected the drug-appropriate lever (a quantal measure). The present findings indicate that manipulating motivation for food minimally impacts d-amphetamine discrimination, however, the range of conditions used to examine the effects of motivating operations on stimulus control by d-amphetamine drugs and other drugs is limited and the topic may warrant further investigation.

  15. Oral Fluid with Three Modes of Collection and Plasma Methamphetamine and Amphetamine Enantiomer Concentrations After Controlled Intranasal l-Methamphetamine Administration

    OpenAIRE

    Newmeyer, Matthew N.; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A.; Huestis, Marilyn A.

    2015-01-01

    Methamphetamine is included in drug testing programs due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks VapoInhaler administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices a...

  16. The use of cyclohexanone as a "derivatizing" reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine.

    Science.gov (United States)

    El-Haj, B M; Al-Amri, A M; Hassan, M H; Ali, H S; Bin Khadem, R K

    2003-07-29

    A GC-MS method has been developed for the detection of amphetamine, methamphetamine, and the ephedrines, in seizures and the urine, based on on-GC condensation (derivatization) with cyclohexanone. The method is simple: the dried seizure material or the urine extract was mixed with cyclohexanone and injected into the GC-MS. The method was found to be superior to the methods based on acyl and trimethylsilyl (TMS) derivatization. Unlike for the acyl and TMS derivatives, the molecular and fragment ions of the cyclohexanone condensation products (cyclohexanone derivatives) were of substantial abundance, a useful property in unambiguous compound characterization. Furthermore, the high stability of the "derivatizing" reagent, cyclohexanone, compared with acyl and TMS derivatizing reagents, is a useful property in method development. The present method has proved selective and, tentatively, sensitive enough in the following areas (where methods based on acyl and TMS derivatization, as tested in this laboratory, have failed): (a) detection of amphetamine as a metabolite of methamphetamine; (b) detection of norpseudoephedrine as a metabolite of pseudoephedrine; (c) detection of amphetamine as an impurity of methamphetamine; (d) detection of cathine (norephedrine) as a constituent of Khat leaves; and (e) differentiation of Khat use from phenylpropanolamine use.

  17. Presentation of regional cerebral blood flow in amphetamine abusers by [sup 99]Tc[sup m]-HMPAO brain SPECT. [Hexamethylpropyleneamine oxide

    Energy Technology Data Exchange (ETDEWEB)

    Kao, C.H.; Wang, S.J.; Yeh, S.H. (Taichung Veterans General Hospital, Taiwan (China). Dept. of Nuclear Medicine)

    1994-02-01

    The aim of this study was to describe the effectiveness of [sup 99]Tc[sup m]-hexamethylpropyleneamine oxime ([sup 99]Tc[sup m]-HMPAO) brain single photon emission computed tomography (SPECT) in the assessment of the regional cerebral blood flow (rCBF) in amphetamine abusers. Twenty-one amphetamine abusers were included and [sup 99]Tc[sup m]-HMPAO brain SPECT performed to evaluate rCBF. The drug-using periods ranged from 1 month to several years. The demonstrated neuropsychogenic symptoms and signs of the abusers were from normal presentation to various neurologic complications. The brain SPECT scans were interpreted visually as either normal or abnormal. The degree of abnormality was classified into mild or severe. The results revealed that (a) most SPECT studies in abusers show small defects (95%, 20/21 cases); 71% (15/21) of cases revealed multiple defects over both hemispheres (classified as severe); 24% (5/21) of the cases had focal defects (classified as mild); and only one case (5%, 1/21) demonstrated a normal SPECT finding; (b) the degree of abnormality on SPECT scans was not related to the dose and duration of drug use or the severity of the neuropsychiatric symptoms and signs. In conclusion, [sup 99]Tc[sup m]-HMPAO brain SPECT is a sensitive but not specific test for neuropsychogenic abnormalities associated with amphetamine abuse. (Author).

  18. Screening determination of four amphetamine-type drugs in street-grade illegal tablets and urine samples by portable capillary electrophoresis with contactless conductivity detection.

    Science.gov (United States)

    Nguyen, Thi Anh Huong; Pham, Thi Ngoc Mai; Ta, Thi Thao; Nguyen, Xuan Truong; Nguyen, Thi Lien; Le, Thi Hong Hao; Koenka, Israel Joel; Sáiz, Jorge; Hauser, Peter C; Mai, Thanh Duc

    2015-12-01

    A simple and inexpensive method for the identification of four substituted amphetamines, namely, 3,4-methylenedioxy methamphetamine (MDMA), methamphetamine (MA), 3,4-methylenedioxy amphetamine (MDA) and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) was developed using an in-house constructed semi-automated portable capillary electrophoresis instrument (CE) with capacitively coupled contactless conductivity detection (C(4)D). Arginine 10mM adjusted to pH4.5 with acetic acid was found to be the optimal background electrolyte for the CE-C(4)D determination of these compounds. The best detection limits achieved with and without a sample preconcentration process were 10ppb and 500ppb, respectively. Substituted amphetamines were found in different seized illicit club drug tablets and urine samples collected from different suspected users. Good agreement between results from CE-C(4)D and those with the confirmation method (GC-MS) was achieved, with correlation coefficients for the two pairs of data of more than 0.99.

  19. Electrokinetic extraction on artificial liquid membranes of amphetamine-type stimulants from urine samples followed by high performance liquid chromatography analysis.

    Science.gov (United States)

    Seidi, Shahram; Yamini, Yadollah; Baheri, Tahmineh; Feizbakhsh, Rouhollah

    2011-07-01

    Electromembrane extraction (EME) coupled with high performance liquid chromatography and ultraviolet detection was developed for determination of amphetamine-type stimulants in human urine samples. Amphetamines migrated from 3 mL of different human urine matrices, through a thin layer of 2-nitrophenyl octyl ether (NPOE) containing 15% tris-(2-ethylhexyl) phosphate (TEHP) immobilized in the pores of a porous hollow fiber, and into a 15 μL acidic aqueous acceptor solution present inside the lumen of the fiber. Equilibrium extraction conditions were obtained after 7 min of operation. Experimental design and response surface methodology (RSM) were used for optimization of EME parameters. Under optimal conditions, amphetamines were effectively extracted with recoveries in the range of 54-70%, which corresponded to preconcentration factors in the range of 108-140. The calibration curves were investigated in the range of 0-7 μg mL(-1) and good linearity was achieved with a coefficient of estimation better than 0.991. Detection limits and inter-day precision (n=3) were less than 0.01 μg mL(-1) and 11.2%, respectively.

  20. Screening for urinary amphetamine and analogs by capillary electrophoretic immunoassays and confirmation by capillary electrophoresis with on-column multiwavelength absorbance detection.

    Science.gov (United States)

    Ramseier, A; Caslavska, J; Thormann, W

    1998-11-01

    This paper characterizes competitive binding, electrokinetic capillary-based immunoassays for screening of urinary amphetamine (A) and analogs using reagents which were commercialized for a fluorescence polarization immunoassay (FPIA). After incubation of 25 microL urine with the reactants, a small aliquot of the mixture is applied onto a fused-silica capillary and unbound fluorescein-labeled tracer compounds are monitored by capillary electrophoresis with on-column laser-induced fluorescence detection. Configurations in presence and absence of micelles were investigated and found to be capable of recognizing urinary D-(+)-amphetamine at concentrations > about 80 ng/mL. Similar responses were obtained for racemic methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). The electrokinetic immunoassay data suggest that the FPIA reagent kit includes two immunoassay systems (two antibodies and two tracer molecules), one that recognizes MA and MDMA, and one that is geared towards monitoring of A. For confirmation analysis of urinary amphetamines and ephedrines, capillary electrophoresis in a pH 9.2 buffer and multiwavelength UV detection was employed. The suitability of the electrokinetic methods for screening and confirmation is demonstrated via analysis of patient and external quality control urines.

  1. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic fenproporex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    Science.gov (United States)

    Kraemer, T; Theis, G A; Weber, A A; Maurer, H H

    2000-01-28

    Studies on the metabolism and the toxicological analysis of fenproporex (R,S-3-[(1-phenyl-2-propyl)-amino]-propionitrile, FP) using GC-MS and fluorescence polarization immunoassay are described. The metabolites were identified in urine samples of volunteers by GC-MS after cleavage of conjugates, extraction and acetylation. Besides unchanged FP, fourteen metabolites, including amphetamine, could be identified. Two partially overlapping metabolic pathways could be postulated: ring degradation by one- and two-fold aromatic hydroxylation followed by methylation and side chain degradation by N-dealkylation to amphetamine (AM). A minor pathway leads via beta-hydroxylation of AM to norephedrine. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for FP and 100 ng/ml for AM). Excretion studies showed, that only AM but neither FP nor its specific metabolites were detectable 30-60 h after ingestion of 20 mg of FP. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 58 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  2. Development and validation of a single LC-MS/MS assay following SPE for simultaneous hair analysis of amphetamines, opiates, cocaine and metabolites.

    Science.gov (United States)

    Imbert, L; Dulaurent, S; Mercerolle, M; Morichon, J; Lachâtre, G; Gaulier, J-M

    2014-01-01

    The two major challenges in hair analysis are the limited amount of samples usually available and the low targeted concentrations. To overcome these limitations, a liquid chromatography-electrospray-tandem mass spectrometry method (LC-ESI-MS/MS) allowing the simultaneous analysis of 17 amphetamines (amphetamine, BDB, m-CPP, dexfenfluramine, DOB, DOM, ephedrine, MBDB, MDA, MDEA, MDMA, methamphetamine, methylphenidate, 4-MTA, norephedrine, norfenfluramine and PMA), 5 opiates (morphine, codeine, heroin, ethylmorphine, and 6AM), cocaine and 5 metabolites [ecgonine methyl ester (EME), benzoylecgonine (BZE), anhydroecgonine methyl ester (AME), cocaethylene, and norcocaine] has been developed. The validation procedure included linearity, intra-day and inter-day variability and accuracy for 5 days (5 replicates at 3 concentration levels). Proficiency studies were used to check the accuracy of the method. As a result, all amphetamines, opiates and cocaine derivatives were satisfactory identified by 2 MRM transitions in 15 min. Calibration curves were performed by a quadratic 1/X weighted regression. The calibration model fits from 0.05 to 10 ng/mg. The limits of detection (LODs) range between 0.005 and 0.030 ng/mg. Precision has been checked by intra-day and inter-day RSD, and associated relative bias, which were lower than 25% for the limits of quantifications (LOQs) and lower than 20% for the other levels tested. This method was routinely applied to hair samples: two positive results of adult drug addicts are presented.

  3. The influence of R and S configurations of a series of amphetamine derivatives on quantitative structure-activity relationship models

    Energy Technology Data Exchange (ETDEWEB)

    Fresqui, Maira A.C., E-mail: maira@iqsc.usp.br [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil); Ferreira, Marcia M.C., E-mail: marcia@iqm.unicamp.br [Institute of Chemistry, University of Campinas - UNICAMP, POB 6154, 13083-970 Campinas, SP (Brazil); Trsic, Milan, E-mail: cra612@gmail.com [Institute of Chemistry of Sao Carlos, University of Sao Paulo, Av. Trabalhador Sao-carlense, 400, POB 780, 13560-970 Sao Carlos, SP (Brazil)

    2013-01-08

    Highlights: Black-Right-Pointing-Pointer The QSAR model is not dependent of ligand conformation. Black-Right-Pointing-Pointer Amphetamines were analyzed by quantum chemical, steric and hydrophobic descriptors. Black-Right-Pointing-Pointer CHELPG atomic charges on the benzene ring are one of the most important descriptors. Black-Right-Pointing-Pointer The PLS models built were extensively validated. Black-Right-Pointing-Pointer Manual docking supports the QSAR results by pi-pi stacking interactions. - Abstract: Chiral molecules need special attention in drug design. In this sense, the R and S configurations of a series of thirty-four amphetamines were evaluated by quantitative structure-activity relationship (QSAR). This class of compounds has antidepressant, anti-Parkinson and anti-Alzheimer effects against the enzyme monoamine oxidase A (MAO A). A set of thirty-eight descriptors, including electronic, steric and hydrophobic ones, were calculated. Variable selection was performed through the correlation coefficients followed by the ordered predictor selection (OPS) algorithm. Six descriptors (CHELPG atomic charges C3, C4 and C5, electrophilicity, molecular surface area and log P) were selected for both configurations and a satisfactory model was obtained by PLS regression with three latent variables with R{sup 2} = 0.73 and Q{sup 2} = 0.60, with external predictability Q{sup 2} = 0.68, and R{sup 2} = 0.76 and Q{sup 2} = 0.67 with external predictability Q{sup 2} = 0.50, for R and S configurations, respectively. To confirm the robustness of each model, leave-N-out cross validation (LNO) was carried out and the y-randomization test was used to check if these models present chance correlation. Moreover, both automated or a manual molecular docking indicate that the reaction of ligands with the enzyme occurs via pi-pi stacking interaction with Tyr407, inclined face-to-face interaction with Tyr444, while aromatic hydrogen-hydrogen interactions with Tyr197 are preferable

  4. Neuropharmacology of new psychoactive substances (NPS: focus on the rewarding and reinforcing properties of cannabimimetics and amphetamine-like stimulants

    Directory of Open Access Journals (Sweden)

    Cristina eMiliano

    2016-04-01

    Full Text Available New psychoactive substances (NPS are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, dark net as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society (UNODC, World Drug Report, 2014; EMCDDA, European Drug Report 2014: Trends and developments. The chemical structure (phenethylamines, piperazine, cathinones, tryptamines, synthetic cannabinoids of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%(WDR, 2014. Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone and MDMA analogues. Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ9-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of

  5. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, "dark net") as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ(9)-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated

  6. Evaluation of ¹³C- and ²H-labeled internal standards for the determination of amphetamines in biological samples, by reversed-phase ultra-high performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Berg, Thomas; Karlsen, Morten; Oiestad, Ase Marit Leere; Johansen, Jon Eigill; Liu, Huiling; Strand, Dag Helge

    2014-05-30

    Stable isotope-labeled internal standards (SIL-ISs) are often used when applying liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze for legal and illegal drugs. ISs labeled with (13)C, (15)N, and (18)O are expected to behave more closely to their corresponding unlabeled analytes, compared with that of the more classically used (2)H-labeled ISs. This study has investigated the behavior of amphetamine, (2)H3-, (2)H5, (2)H6-, (2)H8-, (2)H11-, and (13)C6-labeled amphetamine, during sample preparation by liquid-liquid extraction and LC-MS/MS analyses. None or only minor differences in liquid-liquid extraction recoveries of amphetamine and the SIL-ISs were observed. The chromatographic resolution between amphetamine and the (2)H-labeled amphetamines increased with the number of (2)H-substitutes. For chromatographic studies we also included seven additional (13)C6-amphetamines and their analytes. All the (13)C6-labeled ISs were co-eluting with their analytes, both when a basic and when an acidic mobile phase were used. MS/MS analyses of amphetamine and its SIL-ISs showed that the ISs with the highest number of (2)H-substitutes required more energy for fragmentation in the collision cell compared with that of the ISs with a lower number. The findings, in this study, support those of previous studies, showing that (13)C-labeled ISs are superior to (2)H-labeled ISs, for analytical purposes.

  7. Identificação de anfetamina em amostras de cabelo por imunofluorescência polarizada Amphetamine detection in hair samples by FPIA

    Directory of Open Access Journals (Sweden)

    Saulo Rios Mariz

    2003-03-01

    Full Text Available O uso indevido de anfetaminas tem preocupado as autoridades sanitárias em todo o mundo. No Brasil, destacam-se os anorexígenos anfetamínicos como o femproporex, que, no organismo, se biotransforma em anfetamina. Apesar de ser controlado por legislação específica, este fármaco tem sido amplamente utilizado em nosso país. Nas análises toxicológicas para verificação do uso de fármacos e drogas de abuso, têm-se empregado diferentes amostras biológicas. Mais recentemente a utilização do cabelo tem sido preconizada principalmente por informar sobre um uso a longo prazo da substância. A técnica para identificação de anfetaminas em cabelo é a cromatografia em fase gasosa acoplada à espectrometria de massas (CG-EM. A partir de um método descrito na literatura foram desenvolvidos estudos para avaliação da imunofluorescência polarizada como técnica de triagem na identificaçao de anfetamina em cabelo de usuários de anfetamínicos. Os resultados obtidos indicam que o método otimizado pode ser utilizado como triagem na identificação de anfetamina em cabelo.The amphetamine abuse is a preoccupation of public health authorities all over the world. In Brazil, anoretic drugs like fenproporex have been much used. Fenproporex is metabolically dealkylated to amphetamine in the human body. In spite of its legal control, it has been abused in the country. Different samples have been used to identify the drug in toxicological analyses. Hair samples have been proposed recently to identify and study the long-term use of the drug. CG-MG is the technique used to identify amphetamines in hair samples. Following a method proposed in specific literature, some studies have been developed to evaluate the application of the fluorescence polarization imunoassay (FPIA to identify amphetamine in hair samples of fenproporex users. The results show that the standard method may be used as screening in the identification of amphetamine by FPIA in hair

  8. The polymorphisms of bovine cocaine- and amphetamine-regulated transcripts and their associations with cattle (Bos taurus) growth traits

    Indian Academy of Sciences (India)

    Chun Lei Zhang; Hong Chen; Yan Hong Wang; Xian Yong Lan; Chu Zhao Lei; Xing Tang Fang

    2008-09-01

    We investigated the polymorphisms of bovine cocaine- and amphetamine-regulated transcripts (CART). The coding and regulating regions of CART were screened in 7 cattle breeds by the single-stranded conformation polymorphism (SSCP) technique. The four loci (C1, C2, C3 and C4) studied were all polymorphic. Polymerase chain reaction (PCR) products representing different SSCP variants were sequenced and a total of 9 single-nucleotide polymorphisms (SNPs) were found. The associations between polymorphic loci and the growth traits of Nanyang cattle were analysed. The results indicated that genotype A1A1 of the C1 locus was associated with a higher body weight ( < 0.05) than heterozygous A1B1. Genotype A2A2 of the C2 locus was associated with lower body weight and average daily weight gain ( ≤ 0.001) than heterozygous A2B2. C3 and C4 loci had no significant effect on Nanyang cattle growth traits (P > 0.05).

  9. Enantiomeric separation of 13 new amphetamine-like designer drugs by capillary electrophoresis, using modified-B-cyclodextrins.

    Science.gov (United States)

    Burrai, Lucia; Nieddu, Maria; Pirisi, Maria Antonietta; Carta, Antonio; Briguglio, Irene; Boatto, Gianpiero

    2013-10-01

    An easy-to-prepare chiral CE method for the enantiomeric separation of 13 new amphetamine-like designer drugs, using CDs as chiral selectors, was developed. Sulfated-β-CD was found to be the best chiral selector among the three used (sulfated-β-CD, caroboxymethyl-β-CD, dimethyl-β-CD). The separation of the analytes was achieved in a fused-silica gel capillary at 20 °C using an applied voltage of +25 kV. The optimized background electrolyte consisted of 63.5 mM H3 PO4 and 46.9 mM NaOH in water. Several electrophoretic parameters such as CD type, CD concentration (1 - 40 mg/mL), buffer pH (2.6, 3.6, 5.0, 6.0), length of the capillary (70 - 40 cm total length), amount of the organic solvent (methanol and acetonitrile) were investigated and optimized.

  10. Estimation of the measurement uncertainty by the bottom-up approach for the determination of methamphetamine and amphetamine in urine.

    Science.gov (United States)

    Lee, Sooyeun; Choi, Hyeyoung; Kim, Eunmi; Choi, Hwakyung; Chung, Heesun; Chung, Kyu Hyuck

    2010-05-01

    The measurement uncertainty (MU) of methamphetamine (MA) and amphetamine (AP) was estimated in an authentic urine sample with a relatively low concentration of MA and AP using the bottom-up approach. A cause and effect diagram was deduced; the amount of MA or AP in the sample, the volume of the sample, method precision, and sample effect were considered uncertainty sources. The concentrations of MA and AP in the urine sample with their expanded uncertainties were 340.5 +/- 33.2 ng/mL and 113.4 +/- 15.4 ng/mL, respectively, which means 9.7% and 13.6% of the concentration gave an estimated expanded uncertainty, respectively. The largest uncertainty originated from sample effect and method precision in MA and AP, respectively, but the uncertainty of the volume of the sample was minimal in both. The MU needs to be determined during the method validation process to assess test reliability. Moreover, the identification of the largest and/or smallest uncertainty source can help improve experimental protocols.

  11. Analysis of amphetamines in urine with liquid-liquid extraction by capillary electrophoresis with simultaneous electrochemical and electrochemiluminescence detection.

    Science.gov (United States)

    Sun, Jinying; Xu, Xiaoyu; Wang, Chunyan; You, Tianyan

    2008-10-01

    Amphetamines including methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine were separated and detected by CE using simultaneous electrochemical (EC) and electrochemiluminescence (ECL) detection (CE-EC/ECL). Factors that influenced the separation and detection performance, such as the detection potential, the pH value and concentration of the running buffer, the separation voltage and the pH of the detection buffer, were investigated. LODs of 3.3x10(-8) mol/L (0.16 fmol), 1.6x10(-7) mol/L (0.78 fmol) and 3.3x10(-8) mol/L (0.16 fmol) were obtained for methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine, respectively. For practical application, a liquid-liquid extraction with ethyl acetate procedure was developed for urine sample pretreatment and extraction efficiencies higher than 90% were obtained. The established simultaneous CE-EC/ECL was successfully applied for urine sample analysis.

  12. Determination of amphetamines in human urine by liquid chromatography with fluorimetric detection using a solid-phase extraction procedure.

    Science.gov (United States)

    Bugamelli, Francesca; Mandrioli, Roberto; Cavallini, Annalisa; Baccini, Cesare; Conti, Matteo; Raggi, Maria Augusta

    2006-10-01

    A precise and feasible HPLC method has been developed for the analysis of amphetamine (AMPH), methamphetamine (MAMPH) and methylenedioxymethamphetamine (MDMA, ecstasy) in human urine. A chromatographic run on a C8 Genesis (150 mm x 4.6 mm, 5 microm) column maintained at 30 degrees C lasts about 17 min, using a mobile phase composed of ACN (12%) and a pH 2.5 phosphate buffer (88%) containing 0.3% triethylamine. Mirtazapine was used as the internal standard. Good linearity was found in the 100-2000 ng/mL concentration range for AMPH and MAMPH and in the 12-2000 ng/mL concentration range for MDMA. The pretreatment of urine samples was carried out by means of a careful SPE procedure on C2 cartridges. The extraction yields were very satisfactory for all analytes, with average values greater than 97%. The leading conditions allowed the determination of AMPH, MAMPH and MDMA with satisfactory precision and accuracy. The method has been successfully applied to the determination of the analytes in urine of AMPH users.

  13. Replacing immunoassays for mephedrone, ketamines and six amphetamine-type stimulants with flow injection analysis tandem mass spectrometry.

    Science.gov (United States)

    Lua, Ingrid A; Lin, Shiou-Ling; Lin, Huei R; Lua, Ahai C

    2012-10-01

    A screening procedure was developed for the simultaneous detection of mephedrone, six amphetamine-type stimulants (ATS), ketamine and its two metabolites with electrospray ionization flow injection analysis tandem mass spectrometry (FIA-MS-MS). Urine samples were fortified with deuterated analogues as internal standards, extracted with ethyl acetate and analyzed with FIA-MS-MS. The mass analyzer was operated in multiple reaction monitoring mode. Two product ions were monitored for each drug and internal standards. For each analyte, the limit of detection was less than 4 µg/L, within-day and between-day precisions (percent coefficient of variation) at three different concentrations were less than 7.3% and bias was between -17.3 and 11.8%. Total analysis time with FIA-MS-MS is 1.8 min per sample. A group of 215 urine samples were screened with immunoassay for ATS and analyzed with FIA-MS-MS and gas chromatography-mass spectrometry (GC-MS) for ketamines and ATS. The analysis of ATS by immunoassay and GC-MS was 96.7% concordant. The analysis of three ketamines and seven ATS by FIA-MS-MS and GC-MS was 97.2% concordant. The FIA-MS-MS procedure is efficient, accurate, flexible and capable of detecting analytes of different chemical groups. It can replace immunoassays for the screening of new designer drugs when commercial immunoassays are unavailable.

  14. One Hundred False-Positive Amphetamine Specimens Characterized by Liquid Chromatography Time-of-Flight Mass Spectrometry

    Science.gov (United States)

    Marin, Stephanie J.; Doyle, Kelly; Chang, Annie; Concheiro-Guisan, Marta; Huestis, Marilyn A.; Johnson-Davis, Kamisha L.

    2016-01-01

    Some amphetamine (AMP) and ecstacy (MDMA) urine immunoassay (IA) kits are prone to false-positive results due to poor specificity of the antibody. We employed two techniques, high-resolution mass spectrometry (HRMS) and an in silico structure search, to identify compounds likely to cause false-positive results. Hundred false-positive IA specimens for AMP and/or MDMA were analyzed by an Agilent 6230 time-of-flight (TOF) mass spectrometer. Separately, SciFinder (Chemical Abstracts) was used as an in silico structure search to generate a library of compounds that are known to cross-react with AMP/MDMA IAs. Chemical formulas and exact masses of 145 structures were then compared against masses identified by TOF. Compounds known to have cross-reactivity with the IAs were identified in the structure-based search. The chemical formulas and exact masses of 145 structures (of 20 chemical formulas) were compared against masses identified by TOF. Urine analysis by HRMS correlates accurate mass with chemical formulae, but provides little information regarding compound structure. Structural data of targeted antigens can be utilized to correlate HRMS-derived chemical formulas with structural analogs. PMID:26342055

  15. Wide-field diffuse amacrine cells in the monkey retina contain immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART).

    Science.gov (United States)

    Long, Ye; Bordt, Andrea S; Liu, Weiley S; Davis, Elizabeth P; Lee, Stephen J; Tseng, Luke; Chuang, Alice Z; Whitaker, Christopher M; Massey, Stephen C; Sherman, Michael B; Marshak, David W

    2016-10-01

    The goals of this study were to localize the neuropeptide Cocaine- and Amphetamine-Regulated Transcript (CART) in primate retinas and to describe the morphology, neurotransmitter content and synaptic connections of the neurons that contain it. Using in situ hybridization, light and electron microscopic immunolabeling, CART was localized to GABAergic amacrine cells in baboon retinas. The CART-positive cells had thin, varicose dendrites that gradually descended through the inner plexiform layer and ramified extensively in the innermost stratum. They resembled two types of wide-field diffuse amacrine cells that had been described previously in macaque retinas using the Golgi method and also A17, serotonin-accumulating and waterfall cells of other mammals. The CART-positive cells received synapses from rod bipolar cell axons and made synapses onto the axons in a reciprocal configuration. The CART-positive cells also received synapses from other amacrine cells. Some of these were located on their primary dendrites, and the presynaptic cells there included dopaminergic amacrine cells. Although some CART-positive somas were localized in the ganglion cell layer, they did not contain the ganglion cell marker RNA binding protein with multiple splicing (RBPMS). Based on these results and electrophysiological studies in other mammals, the CART-positive amacrine cells would be expected to play a major role in the primary rod pathway of primates, providing feedback inhibition to rod bipolar cells.

  16. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats.

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    Andrzejewski, Matthew E; Spencer, Robert C; Harris, Rachel L; Feit, Elizabeth C; McKee, Brenda L; Berridge, Craig W

    2014-04-01

    Low dose amphetamine (AMPH) and methylphenidate (MPH, Ritalin(®)) are the most widely prescribed and most effective pharmacotherapy for attention-deficit/hyperactivity disorder (ADHD). Certain low, clinically relevant doses of MPH improve sustained attention and working memory in normal rats, in contrast to higher doses that impair cognitive ability and induce locomotor activity. However, the effects of AMPH of MPH on sustained attention and behavioral inhibition remain poorly characterized. The present experiments examined the actions of AMPH (0.1 and 0.25 mg/kg) and MPH (0.5 and 1.0 mg/kg) in a rat model of 1) sustained attention, where signal and blank trials were interspersed randomly and occurred at unpredictable times, and 2) behavioral inhibition, using a differential reinforcement of low rate (DRL) schedule. In a signal detection paradigm, both 0.5 mg/kg and 1.0 mg/kg MPH and 0.25 mg/kg AMPH improve sustained attention, however neither AMPH nor MPH improve behavioral inhibition on DRL. Taken together with other recent studies, it appears that clinically-relevant doses of AMPH and MPH may preferentially improve attention-related behavior while having little effect on behavioral inhibition. These observations provide additional insight into the basic behavioral actions of low-dose psychostimulants and further suggest that the use of sustained attention tasks may be important in the development of novel pharmacological treatments for ADHD.

  17. Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine.

    Science.gov (United States)

    Kuhn, Fábio Teixeira; Trevizol, Fabíola; Dias, Verônica Tironi; Barcelos, Raquel Cristine Silva; Pase, Camila Simonetti; Roversi, Karine; Antoniazzi, Caren Tatiane de David; Roversi, Katiane; Boufleur, Nardeli; Benvegnú, Dalila Moter; Emanuelli, Tatiana; Bürger, Marilise Escobar

    2015-01-01

    Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.

  18. Comparison of five derivatizing agents for the determination of amphetamine-type stimulants in human urine by extractive acylation and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Dobos, Adrienn; Hidvégi, Elod; Somogyi, Gábor Pál

    2012-06-01

    Five acylation reagents have been compared for use as derivatizing agents for the analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride, pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA) and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine, methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution and saturated NaHCO(3) solution. The sample was then extracted with dichloromethane and the derivatizing agent and 2 µL were injected into the GC-MS instrument. The derivatizing agents were compared with reference to the signal-to-noise (S/N) ratios, peak area values, relative standard deviations (RSDs), linearities, limits of detection (LODs) and selectivities. The acetic anhydride proved to be the best according to the S/N ratio and peak area results for amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N ratios at 3 µg/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20 µg/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD results for MA, MDMA and MDEA were produced by AA.

  19. A Preliminary Investigation of Individual Differences in Subjective Responses to D-Amphetamine, Alcohol, and Delta-9-Tetrahydrocannabinol Using a Within-Subjects Randomized Trial.

    Directory of Open Access Journals (Sweden)

    Margaret C Wardle

    Full Text Available Polydrug use is common, and might occur because certain individuals experience positive effects from several different drugs during early stages of use. This study examined individual differences in subjective responses to single oral doses of d-amphetamine, alcohol, and delta-9-tetrahydrocannabinol (THC in healthy social drinkers. Each of these drugs produces feelings of well-being in at least some individuals, and we hypothesized that subjective responses to these drugs would be positively correlated. We also examined participants' drug responses in relation to personality traits associated with drug use. In this initial, exploratory study, 24 healthy, light drug users (12 male, 12 female, aged 21-31 years, participated in a fully within-subject, randomized, counterbalanced design with six 5.5-hour sessions in which they received d-amphetamine (20mg, alcohol (0.8 g/kg, or THC (7.5 mg, each paired with a placebo session. Participants rated the drugs' effects on both global measures (e.g. feeling a drug effect at all and drug-specific measures. In general, participants' responses to the three drugs were unrelated. Unexpectedly, "wanting more" alcohol was inversely correlated with "wanting more" THC. Additionally, in women, but not in men, "disliking" alcohol was negatively correlated with "disliking" THC. Positive alcohol and amphetamine responses were related, but only in individuals who experienced a stimulant effect of alcohol. Finally, high trait constraint (or lack of impulsivity was associated with lower reports of liking alcohol. No personality traits predicted responses across multiple drug types. Generally, these findings do not support the idea that certain individuals experience greater positive effects across multiple drug classes, but instead provide some evidence for a "drug of choice" model, in which individuals respond positively to certain classes of drugs that share similar subjective effects, and dislike other types

  20. Chiral separation of cathinone and amphetamine derivatives by HPLC/UV using sulfated ß-cyclodextrin as chiral mobile phase additive.

    Science.gov (United States)

    Taschwer, Magdalena; Seidl, Yvonne; Mohr, Stefan; Schmid, Martin G

    2014-08-01

    In the last years the identification of new legal and illegal highs has become a huge challenge for the police and prosecution authorities. In an analytical context, only a few analytical methods are available to identify these new substances. Moreover, many of these recreational drugs are chiral and it is supposed that the enantiomers differ in their pharmacological potency. Since nonenantioselective synthesis is easier and cheaper, they are mainly sold as racemic mixtures. The goal of this research work was to develop an inexpensive method for the chiral separation of cathinones and amphetamines. This should help to discover if the substances are sold as racemic mixtures and give further information about their quality as well as their origin. Chiral separation of a set of 6 amphetamine and 25 cathinone derivatives, mainly purchased from various Internet shops, is presented. A LiChrospher 100 RP-18e, 250 x 4 mm, 5 µm served as the stationary phase. The chiral mobile phase consisted of methanol, water, and sulfated ß-cyclodextrin. Measurements were performed under isocratic conditions in reversed phase mode using UV detection. Four model compounds of the two substance classes were used to optimize the mobile phase. Under final conditions (methanol:water 2.5:97.5 + 2% sulfated ß-cyclodextrin) enantiomers of amphetamine and five derivatives were baseline separated within 23 min. In all, 17 cathinones were completely or partially chirally separated. However, as only 3 of 25 cathinones were baseline resolved, the application of this method is limited for cathinone analogs. Additionally, the results were compared with an RP-8e column.

  1. Acute total sleep deprivation potentiates amphetamine-induced locomotor-stimulant effects and behavioral sensitization in mice.

    Science.gov (United States)

    Saito, Luis P; Fukushiro, Daniela F; Hollais, André W; Mári-Kawamoto, Elisa; Costa, Jacqueline M; Berro, Laís F; Aramini, Tatiana C F; Wuo-Silva, Raphael; Andersen, Monica L; Tufik, Sergio; Frussa-Filho, Roberto

    2014-02-01

    It has been demonstrated that a prolonged period (48 h) of paradoxical sleep deprivation (PSD) potentiates amphetamine (AMP)-induced behavioral sensitization, an animal model of addiction-related neuroadaptations. In the present study, we examined the effects of an acute short-term deprivation of total sleep (TSD) (6h) on AMP-induced behavioral sensitization in mice and compared them to the effects of short-term PSD (6 h). Three-month-old male C57BL/6J mice underwent TSD (experiment 1-gentle handling method) or PSD (experiment 2-multiple platforms method) for 6 h. Immediately after the sleep deprivation period, mice were tested in the open field for 10 min under the effects of saline or 2.0 mg/kg AMP. Seven days later, to assess behavioral sensitization, all of the mice received a challenge injection of 2.0 mg/kg AMP and were tested in the open field for 10 min. Total, peripheral, and central locomotion, and grooming duration were measured. TSD, but not PSD, potentiated the hyperlocomotion induced by an acute injection of AMP and this effect was due to an increased locomotion in the central squares of the apparatus. Similarly, TSD facilitated the development of AMP-induced sensitization, but only in the central locomotion parameter. The data indicate that an acute period of TSD may exacerbate the behavioral effects of AMP in mice. Because sleep architecture is composed of paradoxical and slow wave sleep, and 6-h PSD had no effects on AMP-induced hyperlocomotion or sensitization, our data suggest that the deprivation of slow wave sleep plays a critical role in the mechanisms that underlie the potentiating effects of TSD on both the acute and sensitized addiction-related responses to AMP.

  2. Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

    2010-08-01

    Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

  3. Signaling Mechanisms in the Nitric Oxide Donor- and Amphetamine-Induced Dopamine Release in Mesencephalic Primary Cultured Neurons.

    Science.gov (United States)

    Salum, Cristiane; Schmidt, Fanny; Michel, Patrick P; Del-Bel, Elaine; Raisman-Vozari, Rita

    2016-01-01

    Previous research has shown that nitric oxide (NO) synthase inhibitors prevent rodents' sensorimotor gating impairments induced by dopamine releasing drugs, such as amphetamine (Amph) and methylphenidate. The mechanisms of this effect have not been entirely understood. In the present work, we investigated some possible mechanisms by which the NO donor, NOC-12 (3-ethyl-3-(ethylaminoethyl)-1-hydroxy-2-oxo-1-triazene), influence spontaneous and Amph-induced dopamine release, using rat mesencephalic primary cultured neurons preparations. Our results showed that NOC-12 increased dopamine release in a concentration-dependent manner and potentiated the Amph-induced one. Dopamine release induced by NOC-12 was disrupted by N-acetyl-L-cystein (NAC-a free radical scavenger) and MK-801, a NMDA (N-methyl-D-aspartate) non-competitive antagonist, and was concentration dependently affected by oxadiazolo[4,3]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (sGC). In contrast, dopamine released by Amph was facilitated by NAC and by MK-801 and not affected by nifedipine (a L-type-Ca(+2) channel blocker), which enhanced NOC-12-induced dopamine release. The present work demonstrates that DA release induced by NOC-12 is partially dependent on sGC and on NMDA activation, and is modulated by L-type Ca(+2) channel and the antioxidant NAC. This mechanism differs from the Amph-induced one, which appears not to depend on L-type Ca(+2) channel and seems to be facilitated by NMDA channel blocking and by NAC. These results suggest that Amph and NOC-12 induce dopamine release through complementary pathways, which may explain the potentiation of Amph-induced dopamine release by NOC-12. These findings contribute to understand the involvement of NO in dopamine-related neuropsychiatric and neurodegenerative diseases.

  4. Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach.

    Science.gov (United States)

    Blaiss, Cory A; Janak, Patricia H

    2007-05-01

    The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.

  5. D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors.

    Science.gov (United States)

    Bay-Richter, C; O'Callaghan, M J; Mathur, N; O'Tuathaigh, C M P; Heery, D M; Fone, K C F; Waddington, J L; Moran, P M

    2013-07-01

    Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2-/-), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2-/-. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2-/-. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1-/-), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2-/-. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes.

  6. Validation of analysis of amphetamines, opiates, phencyclidine, cocaine, and benzoylecgonine in oral fluids by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Kala, Subbarao V; Harris, Steve E; Freijo, Tom D; Gerlich, Stan

    2008-10-01

    The aim of the present study was to develop and validate a method for the detection and quantitation of drugs of abuse in oral fluids. Fortified oral fluid samples (made in-house) and samples from donors collected with Quantasil oral fluid collection kits from Immunalysis were screened on an Olympus 5400 using reagents purchased from Immunalysis. Amphetamines (AMPs), opiates, phencyclidine (PCP), and cocaine and its metabolite benzoylecgonine (BE) in oral fluids were quantitated by an Applied Biosystems 3200 QTRAP liquid chromatograph-tandem mass spectrometer (LC-MS-MS). AMPs, opiates, PCP, cocaine, and BE were extracted from samples using liquid-liquid or solid-phase extractions and the extracts were separated on a Shimadzu high-performance liquid chromatograph prior to the MS-MS analysis. For each drug, two multiple reaction mode transitions were monitored using positive electrospray ionization coupled to an MS-MS detector. Corresponding d3, d5, d6, and d11 internal standards were used to quantitate the results. The limit of detection/quantitation for AMPs, opiates, PCP, cocaine, and its metabolite BE were 10, 10, 2, 2, and 2 ng/mL of oral fluid, respectively, on a signal-to-noise ratio > 4. This corresponded to 25, 25, 5, 5, and 5 pg on column. The method was verified by participating in the North America Oral Fluid Proficiency Testing administered by Research Triangle Institute and by analyzing real samples from donors. In conclusion, LC-MS-MS provided a simple way to analyze and quantitate drugs of abuse in oral fluids.

  7. A one-step extraction procedure for the screening of cocaine, amphetamines and cannabinoids in postmortem blood samples.

    Science.gov (United States)

    Pelição, Fabrício Souza; Peres, Mariana Dadalto; Pissinate, Jauber Fornaciari; De Martinis, Bruno Spinosa

    2014-01-01

    A gas chromatography-mass spectrometric (GC-MS) method was developed and validated for the simultaneous detection and quantification in postmortem whole blood samples of cocaine (COC), amphetamines (AMPs) and cannabis; the main drugs involved in cases of impaired driving in Brazil. The analytes were extracted by solid-phase extraction by means of Bond-Elute Certify cartridges, derivatized with N-methyl-N-(trimethylsilyl)trifluoroacetamide at 80°C for 30 min and analyzed by GC-MS. Linearity ranged from 10 to 500 ng/mL, except for ecgonine methyl ester, for which linearity ranged from 10 to 100 ng/mL. Inter- and intra-day imprecision ranged from 2.8 to 18.4% and from 1.5 to 14.9%, respectively. Accuracy values lay between 86.9 and 104.4%. The limit of quantitation for all drugs was 10 ng/mL and recoveries were >74% for all analytes, except for cannabinoids, which showed poor recovery (∼30%). The developed method was applied to real samples collected from deceased victims due to traffic accidents. These samples were selected according to the results obtained in immunoassay screening on collected urine samples. Five samples were positive for the presence of COC and metabolites, four samples were positive for cannabinoids, six samples were positive for AMPs and two samples were drug negative. Some samples were positive for more than one class of drug. Results obtained from whole blood samples showed good agreement with urine screening. The developed method proved capable of quantifying all three classes of drugs of abuse proposed in this study, through a one-step extraction procedure.

  8. In-sample derivatization-solid-phase microextraction of amphetamines and ecstasy related stimulants from water and urine.

    Science.gov (United States)

    Racamonde, Inés; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2013-04-03

    A solid-phase microextraction (SPME) method for the determination of five amphetamine type stimulants (ATSs) in water and urine samples is presented. Analytes were simultaneously derivatized with iso-butyl chloroformate (iBCF) in the aqueous sample while being extracted, improving in this way the extractability of ATSs and permitting their determination by gas chromatography-mass spectrometry (GC-MS). The SPME procedure was carefully optimized in order to achieve adequate limits of detection (LODs) for environmental concentrations. Hence, different operational parameters were considered: type of SPME coating, ionic strength, basic catalyzer and derivatizing agent amount, extraction time and temperature. The final SPME procedure consists into the extraction of 100mL of sample containing 2 g of dipotassium monohydrogen phosphate trihydrate and 100 μL of iBCF (1:1 in acetonitrile), for 40 min at 60°C with a polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber. Under these conditions, LODs in wastewater ranged from 0.4 to 2 ng L(-1), relative recoveries in the 84-114% range and relative standard deviations (RSD) lower than 15% were obtained. The application of the method to wastewater and river water samples showed the ecstasy ATS, 3,4-methylenedioxymethamphetamine (MDMA), as the most frequently detected, followed by methamphetamine, in concentrations around 20 ng L(-1). Finally, the method was downscaled and also validated with urine samples, proving its good performance with this matrix too: RSD<11%, recoveries in the 98-110% range and LODs lower than 0.1 μg L(-1).

  9. Cocaine- and amphetamine-regulated transcript and calcium binding proteins immunoreactivity in the subicular complex of the guinea pig.

    Science.gov (United States)

    Wasilewska, Barbara; Najdzion, Janusz; Równiak, Maciej; Bogus-Nowakowska, Krystyna; Hermanowicz, Beata; Kolenkiewicz, Małgorzata; Żakowski, Witold; Robak, Anna

    2016-03-01

    In this study we present the distribution and colocalization pattern of cocaine- and amphetamine-regulated transcript (CART) and three calcium-binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV) in the subicular complex (SC) of the guinea pig. The subiculum (S) and presubiculum (PrS) showed higher CART-immunoreactivity (-IR) than the parasubiculum (PaS) as far as the perikarya and neuropil were concerned. CART- IR cells were mainly observed in the pyramidal layer and occasionally in the molecular layer of the S. In the PrS and PaS, single CART-IR perikarya were dispersed, however with a tendency to be found only in superficial layers. CART-IR fibers were observed throughout the entire guinea pig subicular neuropil. Double-labeling immunofluorescence showed that CART-IR perikarya, as well as fibers, did not stain positively for any of the three CaBPs. CART-IR fibers were only located near the CB-, CR-, PV-IR perikarya, whereas CART-IR fibers occasionally intersected fibers containing one of the three CaBPs. The distribution pattern of CART was more similar to that of CB and CR than to that of PV. In the PrS, the CART, CB and CR immunoreactivity showed a laminar distribution pattern. In the case of the PV, this distribution pattern in the PrS was much less prominent than that of CART, CB and CR. We conclude that a heterogeneous distribution of the CART and CaBPs in the guinea pig SC is in keeping with findings from other mammals, however species specific differences have been observed.

  10. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin on food intake regulation in lean mice

    Directory of Open Access Journals (Sweden)

    Kiss Alexander

    2008-10-01

    Full Text Available Abstract Background CART (cocaine- and amphetamine-regulated transcript peptide and cholecystokinin (CCK are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS, the paraventricular nucleus (PVN, and the dorsomedial nucleus (DMH of the hypothalamus. Results In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102 in the doses of 0.1 or 0.5 μg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 μg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102 on food intake. After simultaneous administration of 0.1 μg/mouse CART(61-102 and of 4 μg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102 and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test. Conclusion The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.

  11. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

    2013-04-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity.

  12. Immunoreactivity to cocaine- and amphetamine-regulated transcript in the enteric nervous system of the pig and wild boar stomach.

    Science.gov (United States)

    Zacharko-Siembida, A; Arciszewski, M B

    2014-02-01

    Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered peptide inducing strong anxiogenic-like effect. CART distribution and its role(s) at periphery are not well understood. Immunohistochemisty was utilized to investigate the distribution patterns of CART in the stomach of the pig and wild boar. Double immunohistochemisty was applied to elucidate whether CART-immunoreactive (IR) neuronal elements coexpress galanin, substance P (SP) and neuropeptide Y (NPY). In the pig stomach, different proportions of CART-IR myenteric neurons were found in the antrum (42.3 ± 3.5%), corpus (18.0 ± 1.9%) and pylorus (33.2 ± 3.0%). CART-IR myeneric neurons were also found in the antrum, corpus and pylorus of the wild boar stomach (41.7 ± 3.2, 36.0 ± 2.2 and 35.8 ± 3.5%; respectively). In both species, none of gastric submucous neurons were CART-IR; however, CART-IR nerve fibres encircled submucous perikarya. In all portions of the pig and wild boar stomach, CART-IR nerve fibres were frequently found in the smooth muscle layer as well as in the lamina muscularis mucosae. In all regions of the pig and wild boar stomach, the expression of galanin and SP was found in CART-IR myenteric neurons and smooth muscle-supplying nerve fibres. CART/NPY coexpression was not found in the porcine stomach; however, in different regions of the wild boar stomach, subpopulations of CART-IR/NPY-IR myenteric neurons were noted. In conclusion, in this study, the existence and distribution patterns of CART in discrete regions of the pig and wild boar stomach were described in details. Colocalization studies revealed that in both animal species, a functional cooperation of CART with several neuropeptides is likely.

  13. Cocaine- and amphetamine-regulated transcript (CART signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.

    Directory of Open Access Journals (Sweden)

    Morgan H James

    Full Text Available BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s of action remains unclear. We investigated the paraventricular thalamus (PVT as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC, medial prefrontal cortex (mPFC and basolateral amygdala (BLA. METHODOLOGY/PRINCIPAL FINDINGS: Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng, CART (0.625 µg or 2.5 µg or no injection, followed by a cocaine prime (10 mg/kg, i.p.. Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. CONCLUSIONS/SIGNIFICANCE: We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.

  14. Depression and dysphoria effects on the interpersonal perception of negative and positive moods and caring relationships: effects of antidepressants, amphetamine, and methylphenidate.

    Science.gov (United States)

    Janowsky, David S

    2003-12-01

    An inverse relationship exists between an individual's degree of negative affect and the interpersonal perception of friendliness, sympathy and empathy, acceptance, warmth, regard, and genuineness, and the converse relationship persists for the perception of sadness and anger. Thus, a "negative interpersonal bias" exists in those with diagnoses of depression or dysphoria. There is evidence that psychostimulants (ie, amphetamine or methylphenidate) and antidepressants can reverse or improve these negative interpersonal perceptions in a positive way, especially in individuals with dysphoria, depression, and anxiety. The theoretic and therapeutic implications of these relationships are discussed herewith.

  15. Relative Bioavailabilities of Lisdexamfetamine Dimesylate and d-Amphetamine in Healthy Adults in an Open-Label, Randomized, Crossover Study After Mixing Lisdexamfetamine Dimesylate With Food or Drink

    Science.gov (United States)

    Ermer, James; Corcoran, Mary; Lasseter, Kenneth

    2016-01-01

    Background: This open-label, crossover study examined lisdexamfetamine dimesylate (LDX) and d-amphetamine pharmacokinetics in healthy adults after administration of an intact LDX capsule or after the capsule was emptied into orange juice or yogurt and the contents consumed. Methods: Healthy adult volunteers (N = 30) were administered a 70-mg LDX capsule or the contents of a 70-mg capsule mixed with yogurt or orange juice using a 3-way crossover design. Blood samples were collected serially for up to 96 hours after dose. Pharmacokinetic endpoints included maximum plasma concentration (Cmax) and area under the plasma concentration versus time curve from zero to infinity (AUC0–∞) or to last assessment (AUClast). Relative LDX and d-amphetamine bioavailabilities from the contents of a 70-mg LDX capsule mixed with orange juice or yogurt were compared with those from the intact LDX capsule using bioequivalence-testing procedures. Results: Geometric least squares mean ratios (90% confidence intervals [CIs]) for d-amphetamine (active moiety) were within the prespecified bioequivalence range (0.80–1.25) when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.971 (0.945, 0.998); AUC0–∞: 0.986 (0.955, 1.019); AUClast: 0.970 (0.937, 1.004)] or yogurt [Cmax: 0.970 (0.944, 0.997); AUC0–∞: 0.945 (0.915, 0.976); AUClast: 0.944 (0.912, 0.977)]. Geometric least squares mean ratios (90% CIs) for LDX (inactive prodrug) were below the accepted range when the contents of a 70-mg LDX capsule were mixed with orange juice [Cmax: 0.641 (0.582, 0.707); AUC0–∞: 0.716 (0.647, 0.792); AUClast: 0.708 (0.655, 0.766)]; the lower 90% CI for Cmax [0.828 (0.752, 0.912)] was below the accepted range when the contents of a 70-mg LDX capsule were mixed with yogurt. Conclusions: Relative bioavailability of d-amphetamine (the active moiety) did not differ across administrations, which suggests that emptying an LDX capsule into orange juice or yogurt and consuming it

  16. Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration.

    Science.gov (United States)

    Newmeyer, Matthew N; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A; Huestis, Marilyn A

    2015-10-01

    Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 μg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results.

  17. 可卡因-苯丙胺调节转录肽与脑缺血研究进展%Research progress on cocaine -amphetamine-regulation transcript and cerebral ischemia

    Institute of Scientific and Technical Information of China (English)

    周肖英; 孙达; 林莉莉

    2015-01-01

    Cocaine -amphetamine-regulated transcript ( CART ) is an endogenous neuropeptide which participates in various physiological functions.In this paper, the function of cocaine-amphetamine-regula-ted transcript and the relationship between CART and cerebral ischemia are reviewed.%可卡因-苯丙胺调节转录肽( CART)是一种内源性神经肽,参与多方面的生理功能。本文就可卡因-苯丙胺调节转录肽的功能及其与脑缺血的研究进展作一综述。

  18. Christmas gingerbread (Lebkuchen) and Christmas cheer--review of the potential role of mood elevating amphetamine-like compounds formed in vivo and in furno.

    Science.gov (United States)

    Idle, J R

    2005-01-01

    The typical spices used in winter include nutmeg, cinnamon, clove and anise. These spices contain two groups of chemicals, the allylbenzenes and their isomers, the propenylbenzenes. It was suggested 40 years ago by Alexander Shulgin that these substances act as metabolic precursors of amphetamines. The biotransformation of these precursors to nitrogen-containing metabolites is reviewed. These reactions have not been reported in humans. Whether or not the pharmacology and toxicology of spices such as nutmeg can be explained on the basis of their allylbenzene or propenylbenzene content is speculative. Humans may be exposed to amphetamines derived from these precursors in forno, the formation during baking and cooking, for example in the preparation of Lebkuchen, or Christmas gingerbread. It is possible that this may be responsible, in part, for uplifting our mood in winter. However, the role of these aromatic substances, acting simply as odours, evoking old memories of winters past, cannot be ignored. Whether spices have a true pharmacological effect or they act as aromatherapy remains to be elucidated through clinical and laboratory studies.

  19. In vivo evidence for greater amphetamine-induced dopamine release in pathological gambling: a positron emission tomography study with [(11)C]-(+)-PHNO.

    Science.gov (United States)

    Boileau, I; Payer, D; Chugani, B; Lobo, D S S; Houle, S; Wilson, A A; Warsh, J; Kish, S J; Zack, M

    2014-12-01

    Drug addiction has been associated with deficits in mesostriatal dopamine (DA) function, but whether this state extends to behavioral addictions such as pathological gambling (PG) is unclear. Here we used positron emission tomography and the D3 receptor-preferring radioligand [(11)C]-(+)-PHNO during a dual-scan protocol to investigate DA release in response to oral amphetamine in pathological gamblers (n=12) and healthy controls (n=11). In contrast with human neuroimaging findings in drug addiction, we report the first evidence that PG is associated with greater DA release in dorsal striatum (54-63% greater [(11)C]-(+)-PHNO displacement) than controls. Importantly, dopaminergic response to amphetamine in gamblers was positively predicted by D3 receptor levels (measured in substantia nigra), and related to gambling severity, allowing for construction of a mechanistic model that could help explain DA contributions to PG. Our results are consistent with a hyperdopaminergic state in PG, and support the hypothesis that dopaminergic sensitization involving D3-related mechanisms might contribute to the pathophysiology of behavioral addictions.

  20. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection.

    Science.gov (United States)

    Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Murakami, Katsunori; Nagao, Masataka; Namura, Akira

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d(5) was used as an internal standard. The linear ranges were 0.01-5.0 microg mL(-1) for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 microg mL(-1) for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation > or = 0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 microg mL(-1) of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio > or = 3) in urine was 5 ng mL(-1) for MA and MDMA and 10 ng mL(-1) for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  1. A new mixed mode solid phase extraction strategy for opioids, cocaines, amphetamines and adulterants in human blood with hybrid liquid chromatography tandem mass spectrometry detection.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam

    2011-04-05

    A rapid method has been developed to analyse morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgonine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, methadone, phenethylamine and levamisole in human blood. Blood samples were cleaned up using mixed mode solid phase extraction using Evolute™ CX solid phase extraction cartridges and the sample aliquots were analysed by hybrid triple quadrupole linear ion trap (QTRAP) mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35 ± 15 in positive mode and MRM ratios. The method was validated in blood, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra. Deuterated analogues of analytes were used as internal standards for quantitation where possible. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines, amphetamines and adulterants in forensic cases of crime offenders, abusers or victims in the Republic of Ireland.

  2. Analysis of amphetamine-type stimulants and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Inoue, Hiroyuki; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Miyauchi, Seiji; Kamo, Naoki

    2008-05-01

    The aim of this work was to develop and validate a method for analysing amphetamine-type stimulants (ATSs) and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry, and to apply it to the pharmacokinetic study of ATSs. 3,4-Methylenedioxymethamphetamine, methamphetamine, ketamine and their main metabolites, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, p-hydroxymethamphetamine, amphetamine and norketamine, were simultaneously quantified by the new method (50-5000 ng/ml). The coefficients of variation and the percent deviations for the eight compounds were in the range of 0.2 to 5.3% and -9.4 to +12.8%, respectively. The recoveries were over 90% in all biological samples tested. This method was effective for the separation and the identification of ATSs and their main metabolites having amine moieties in plasma, urine and bile, and was applicable to pharmacokinetic analysis of methamphetamine, ketamine and their main metabolites in biological samples. This analytical method should be useful for the pharmacokinetic analysis of ATSs.

  3. Confirmation of amphetamine, methamphetamine, MDA and MDMA in urine samples using disk solid-phase extraction and gas chromatography-mass spectrometry after immunoassay screening.

    Science.gov (United States)

    Huang, Zengping; Zhang, Shaoyu

    2003-07-25

    A method using mixed phase disk solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) was developed for confirmation of amphetamine (AMP), methamphetamine (MET), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples after immunoassay screening. Disk SPE provided hydrophobic (C(18)) and strong cation-exchange (SCX) interactions. The analytes were retained on SCX functional groups in the disk and eluted with ammoniated ethyl acetate after washed with methanol. Confirmation and quantitation was exercised by selected ion monitoring using nikethamide as chromatographic standard. Recoveries of the amphetamines were between 73.0 and 104.6% with RSDs in range of 2.1-6.4% (n=3). The limits of detection were 2 ng/ml for AMP, MET and MDMA, and 4 ng/ml for MDA. Five real urine samples were tested with the method after immunoassay screening, and the results were comparable to those of traditional liquid-liquid extraction (LLE). The method was solvent-saved, simple, rapid and reliable, and the extract was cleaner than that of LLE.

  4. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic mefenorex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    Science.gov (United States)

    Kraemer, T; Vernaleken, I; Maurer, H H

    1997-11-21

    Studies on the metabolism and on the toxicological analysis of mefenorex [R,S-N-(3-chloropropyl)-alpha-methylphenethylamine, MF] using gas chromatography-mass spectrometry (GC-MS) and fluorescence polarization immunoassay (FPIA) are described. The metabolites were identified in urine samples of volunteers by GC-MS. Besides MF, thirteen metabolites including amphetamine (AM) could be identified and three partially overlapping metabolic pathways could be postulated. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for MF and 100 ng/ml for AM). Excretion studies showed, that only AM but neither MF nor its specific metabolites were detectable between 32 and 68 h after ingestion of 80 mg of MF. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 68 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  5. Conditioned place preference and locomotor activity in response to methylphenidate, amphetamine and cocaine in mice lacking dopamine D4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Thanos, P.K.; Thanos, P.K.; Bermeo, C.; Rubinstein, M.; Suchland, K.L.; Wang, G.-J.; Grandy, D.K.; Volkow, N.D.

    2010-05-01

    Methylphenidate (MP) and amphetamine (AMPH) are the most frequently prescribed medications for the treatment of attention-deficit/hyperactivity disorder (ADHD). Both drugs are believed to derive their therapeutic benefit by virtue of their dopamine (DA)-enhancing effects, yet an explanation for the observation that some patients with ADHD respond well to one medication but not to the other remains elusive. The dopaminergic effects of MP and AMPH are also thought to underlie their reinforcing properties and ultimately their abuse. Polymorphisms in the human gene that codes for the DA D4 receptor (D4R) have been repeatedly associated with ADHD and may correlate with the therapeutic as well as the reinforcing effects of responses to these psychostimulant medications. Conditioned place preference (CPP) for MP, AMPH and cocaine were evaluated in wild-type (WT) mice and their genetically engineered littermates, congenic on the C57Bl/6J background, that completely lack D4Rs (knockout or KO). In addition, the locomotor activity in these mice during the conditioning phase of CPP was tested in the CPP chambers. D4 receptor KO and WT mice showed CPP and increased locomotor activity in response to each of the three psychostimulants tested. D4R differentially modulates the CPP responses to MP, AMPH and cocaine. While the D4R genotype affected CPP responses to MP (high dose only) and AMPH (low dose only) it had no effects on cocaine. Inasmuch as CPP is considered an indicator of sensitivity to reinforcing responses to drugs these data suggest a significant but limited role of D4Rs in modulating conditioning responses to MP and AMPH. In the locomotor test, D4 receptor KO mice displayed attenuated increases in AMPH-induced locomotor activity whereas responses to cocaine and MP did not differ. These results suggest distinct mechanisms for D4 receptor modulation of the reinforcing (perhaps via attenuating dopaminergic signalling) and locomotor properties of these stimulant drugs

  6. Distribution of cocaine- and amphetamine-regulated transcript in the hippocampal formation of the guinea pig and domestic pig.

    Science.gov (United States)

    Kolenkiewicz, M; Robak, A; Równiak, M; Bogus-Nowakowska, K; Całka, J; Majewski, M

    2009-02-01

    This study provides a detailed description concerning the distribution of cocaineand amphetamine-regulated transcript (CART) subunits - CART(61-102) and rhCART(28-116) - in the hippocampal formation (HF) of the guinea pig and domestic pig, focussing on the dentate gyrus (DG) and hippocampus proper (HP). Although in both studied species CART-immunoreactive (CART-IR) neuronal somata and processes were present generally in the same layers, some species-specific differences were still found. In the granular layer (GL) of both species, the ovalshaped neurons and some thick varicose fibres were encountered. In the guinea pig there was an immunoreactive "band of dots", probably representing crosssectioned terminals within the DG molecular layer (MOL), whereas in the domestic pig, some varicose fibres were detected, thus suggesting a different orientation of, at least, some nerve terminals. Furthermore, some CART-positive cells and fibres were observed in the hilus (HL) of the guinea pig, whereas in the analogical part of the domestic pig only nerve terminals were labelled. In both species, in the pyramidal layer (PL) of the hippocampus proper, CART-IR triangular somata were observed in the CA3 sector, as well as some positive processes in MOL; however, a few immunoreactive perikarya were found only in the CA1 sector of the guinea pig. As regards the localization patterns of two isoforms of CART in the guinea pig, both peptide fragments were present simultaneously in each of the labelled neurons or fibres, whereas in the domestic pig three types of fibres may be distinguished within the area of the DG. In the hilus and MOL of the dentate gyrus, there were fibres expressing both isoforms of CART in their whole length (fibres of the first type). Fibres of the second type (in GL) coexpressed both peptides only on their short segments, and the last ones (in MOL) expressed solely rhCART(28-116). These results indicate that the distribution of the two CART isoforms are

  7. Electrophysiological characteristics of paraventricular thalamic (PVT) neurons in response to cocaine and cocaine- and amphetamine-regulated transcript (CART).

    Science.gov (United States)

    Yeoh, Jiann Wei; James, Morgan H; Graham, Brett A; Dayas, Christopher V

    2014-01-01

    Recent work has established that the paraventricular thalamus (PVT) is a central node in the brain reward-seeking pathway. This role is mediated in part through projections from hypothalamic peptide transmitter systems such as cocaine- and amphetamine-regulated transcript (CART). Consistent with this proposition, we previously found that inactivation of the PVT or infusions of CART into the PVT suppressed drug-seeking behavior in an animal model of contingent cocaine self-administration. Despite this work, few studies have assessed how the basic physiological properties of PVT neurons are influenced by exposure to drugs such as cocaine. Further, our previous work did not assess how infusions of CART, which we found to decrease cocaine-seeking, altered the activity of PVT neurons. In the current study we address these issues by recording from anterior PVT (aPVT) neurons in acutely prepared brain slices from cocaine-treated (15 mg/ml, n = 8) and saline-treated (control) animals (n = 8). The excitability of aPVT neurons was assessed by injecting a series of depolarizing and hyperpolarizing current steps and characterizing the resulting action potential (AP) discharge properties. This analysis indicated that the majority of aPVT neurons exhibit tonic firing (TF), and initial bursting (IB) consistent with previous studies. However, we also identified PVT neurons that exhibited delayed firing (DF), single spiking (SS) and reluctant firing (RF) patterns. Interestingly, cocaine exposure significantly increased the proportion of aPVT neurons that exhibited TF. We then investigated the effects of CART on excitatory synaptic inputs to aPVT neurons. Application of CART significantly suppressed excitatory synaptic drive to PVT neurons in both cocaine-treated and control recordings. This finding is consistent with our previous behavioral data, which showed that CART signaling in the PVT negatively regulates drug-seeking behavior. Together, these studies suggest that cocaine

  8. Electrophysiological characteristics of paraventricular thalamic (PVT) neurons in response to cocaine and cocaine- and amphetamine-regulated transcript (CART)

    Science.gov (United States)

    Yeoh, Jiann Wei; James, Morgan H.; Graham, Brett A.; Dayas, Christopher V.

    2014-01-01

    Recent work has established that the paraventricular thalamus (PVT) is a central node in the brain reward-seeking pathway. This role is mediated in part through projections from hypothalamic peptide transmitter systems such as cocaine- and amphetamine-regulated transcript (CART). Consistent with this proposition, we previously found that inactivation of the PVT or infusions of CART into the PVT suppressed drug-seeking behavior in an animal model of contingent cocaine self-administration. Despite this work, few studies have assessed how the basic physiological properties of PVT neurons are influenced by exposure to drugs such as cocaine. Further, our previous work did not assess how infusions of CART, which we found to decrease cocaine-seeking, altered the activity of PVT neurons. In the current study we address these issues by recording from anterior PVT (aPVT) neurons in acutely prepared brain slices from cocaine-treated (15 mg/ml, n = 8) and saline-treated (control) animals (n = 8). The excitability of aPVT neurons was assessed by injecting a series of depolarizing and hyperpolarizing current steps and characterizing the resulting action potential (AP) discharge properties. This analysis indicated that the majority of aPVT neurons exhibit tonic firing (TF), and initial bursting (IB) consistent with previous studies. However, we also identified PVT neurons that exhibited delayed firing (DF), single spiking (SS) and reluctant firing (RF) patterns. Interestingly, cocaine exposure significantly increased the proportion of aPVT neurons that exhibited TF. We then investigated the effects of CART on excitatory synaptic inputs to aPVT neurons. Application of CART significantly suppressed excitatory synaptic drive to PVT neurons in both cocaine-treated and control recordings. This finding is consistent with our previous behavioral data, which showed that CART signaling in the PVT negatively regulates drug-seeking behavior. Together, these studies suggest that cocaine

  9. CA2+/CALMODULIN-DEPENDENT KINASE II- ASSOCIATES WITH THE C TERMINUS OF THE DOPAMINE TRANSPORTER AND INCREASES AMPHETAMINE-INDUCED DOPAMINE EFFLUX VIA PHOSPHORYLATION OF N-TERMINAL SERINES

    DEFF Research Database (Denmark)

    Fog, Jacob; Khoshbouei, H; Holy, M

    The dopamine transporter(DAT) plays a key role in clearing extracellular dopamine(DA) from the synapse. Moreover DAT is a target for the action of widely abused psychostimulants such as cocaine and amphetamine(AMPH). AMPH is a substrate for the DAT and promotes the reversal of transport and thus...

  10. The effects of d-amphetamine on extrastriatal dopamine D{sub 2}/D{sub 3} receptors: a randomized, double-blind, placebo-controlled PET study with [{sup 11}C]FLB 457 in healthy subjects

    Energy Technology Data Exchange (ETDEWEB)

    Aalto, Sargo [University of Turku, Turku PET Centre, Turku (Finland); Aabo Akademi University, Department of Psychology, Turku (Finland); Hirvonen, Jussi; Kajander, Jaana; Naagren, Kjell; Rinne, Juha O. [University of Turku, Turku PET Centre, Turku (Finland); Kaasinen, Valtteri [University of Turku, Department of Neurology, P.O. Box 52, Turku (Finland); Hagelberg, Nora [University of Turku, Turku PET Centre, Turku (Finland); Turku University Central Hospital, Department of Anaesthesiology, Intensive Care, Emergency Care and Pain Medicine, Turku (Finland); Seppaelae, Timo [Drug Research Unit, National Public Health Institute, Helsinki (Finland); Scheinin, Harry [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Pharmacology, Drug Development and Therapeutics, Turku (Finland); Hietala, Jarmo [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Department of Psychiatry, Turku (Finland)

    2009-03-15

    The dopamine D{sub 2}/D{sub 3} receptor ligand [{sup 11}C]FLB 457 and PET enable quantification of low-density extrastriatal D{sub 2}/D{sub 3} receptors, but it is uncertain whether [{sup 11}C]FLB 457 can be used for measuring extrastriatal dopamine release. We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [{sup 11}C]FLB 457 binding potential (BP{sub ND}) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. The effects of d-amphetamine on [{sup 11}C]FLB 457 BP{sub ND} and distribution volume (V{sub T}) in the frontal cortex were not different from those of placebo. Small decreases in [{sup 11}C]FLB 457 BP{sub ND} were observed only in the posterior cingulate and hippocampus. The regional changes in [{sup 11}C]FLB 457 BP{sub ND} did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D{sub 2}/D{sub 3} receptor binding. Our results indicate that [{sup 11}C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans. (orig.)

  11. Amphetamine induced behavioral alteration and fiber injury in the striatum of mice%苯丙胺致小鼠行为学的变化和纹状体纤维的损伤

    Institute of Scientific and Technical Information of China (English)

    任亚丽; 宿宝贵; 马丽华; 潘三强; 曹长姝; 周立兵

    2012-01-01

    Objective To explore amphetamine-induced behavioral alteration, and fiber injury in the mouse striatum. Methods Mice were randomly divided into the normal, saline and amphetamine groups. The amphetamine group was subdivided into ld,7d, 14 d and 28 d groups. Mice were treated with amphetamine 2 mg·g-1·d-1via intraperitoneal injection in the amphetamine group. Autonomous behavior activities were tested during establishing amphetamine model. Nauta method was used to study the injury of fibers in the mouse striatum induced by amphetamine. Remits Behaviour test showed that total moving distance, average speed, maximum speed, moving fast time/total time in the amphetamine groups at 7, 14 and 28 days were increased as compared with the normal group and saline group (P0.05). Nauta staining demonstrated black degenerated nerve fibers in mouse striatum of amphetamine groups at 14 and 28 days. Conclusions Amphetamine may increase many autonomous behavior activities and cause the degeneration of nerve fibers in the mouse striatum.%目的 探讨苯丙胺对小鼠行为学的变化和纹状体纤维的损伤.方法 雄性C57BL/6小鼠随机分为正常对照组、生理盐水组和苯丙胺组.苯丙胺组又分为1、7、14和28d四个组,腹腔注射苯丙胺2 mg·kg-1·d-1.建模期间对小鼠进行自主行为活动测试.用Nauta法观察纹状体纤维的变化.结果 自主行为学检测发现:用药后,苯丙胺7、14、28 d组的运动总路程、平均速度、最大运动速度、快速运动时间/总时间比正常对照组和生理盐水组增加(P<0.05),而慢速运动时间/总时间在各组间没有显著差异(P>0.05).Nauta法染色显示苯丙胺14d和28d组纹状体内可见变性神经纤维呈黑色,正常组和生理盐水组均未发现变性的神经纤维.结论 苯丙胺可引起小鼠多项活动性指标的增高,及纹状体神经纤维的变性.

  12. Integration of GC/EI-MS and GC/NCI-MS for simultaneous quantitative determination of opiates, amphetamines, MDMA, ketamine, and metabolites in human hair.

    Science.gov (United States)

    Wu, Ya-Hsueh; Lin, Keh-Liang; Chen, Su-Chin; Chang, Yan-Zin

    2008-07-15

    In this paper, the possibility of using a multiple ionization mode approach of GC/MS was developed for the simultaneous hair testing of common drugs of abuse in Asia, including amphetamines (amphetamine, AP; methamphetamine, MA; methylenedioxy amphetamine, MDA; methylenedioxy methamphetamine, MDMA; methylenedioxy ethylamphetamine, MDEA), ketamine (ketamine, K; norketamine, NK), and opiates (morphine, MOR; codeine, COD; 6-acetylmorphine, 6-AM). This strategy integrated the characteristics of gas chromatography-mass spectrometry (GC-MS) using electron impact ionization (EI) and negative chemical ionization (NCI). Hair samples (25 mg) were washed, cut, and incubated overnight at 25 degrees C in methanol-trifluoroacetic acid (methanol-TFA). The samples were extracted by solid phase extraction (SPE) procedure, derivatized using heptafluorobutyric acid anhydride (HFBA) at 70 degrees C for 30 min, and the derivatives analyzed by GC-MS with EI and NCI. The limit of detection (LOD) with GC/EI-MS analysis obtained were 0.03 ng/mg for AP, MA, MDA, MDMA, and MDEA; 0.05 ng/mg for K, NK, MOR, and COD; and 0.08 ng/mg for 6-AM. The LOD of GC/NCI-MS analysis was much lower than GC/EI-MS analysis. The LOD obtained were 30 pg/mg for AP and MDA in GC/EI-MS and 2 pg/mg in GC/NCI-MS. Therefore, the sensitivity of AP and MDA in GC/NCI-MS was improved from 15-fold compared with EI. The sensitivity of AP, MA, MDA, MDMA, MDEA, MOR, and COD was improved from 15- to 60-fold compared with EI. In addition, the sensitivity of 6-AM increased 8-fold through selection of m/z 197 for the quantitative ion. Moreover, K and NK could dramatically improve their sensitivity at 200- and 2000-fold. The integration of GC/EI-MS and GC/NCI-MS can obtain the high sensitivity and complementary results of drugs of abuse in hair. Six hair samples from known drug abusers were examined by this new strategy. These results show that integrating the characteristics of GC/EI-MS and GC/NCI-MS were not only enhancement of

  13. Rapid simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyethylamphetamine in urine by fast gas chromatography-mass spectrometry.

    Science.gov (United States)

    Klette, Kevin L; Jamerson, Matthew H; Morris-Kukoski, Cynthia L; Kettle, Aaron R; Snyder, J Jacob

    2005-10-01

    The use of fast gas chromatography-mass spectrometry (FGC-MS) was investigated to improve the efficiency of analysis of urine specimens that previously screened presumptively positive for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and/or 3,4 methylenedioxyethylamphetamine (MDEA) by immunoassay testing. Specimens were pretreated with basic sodium periodate, extracted using a positive-pressure manifold/cation-exchange solid-phase cartridge methodology, and derivatized using 4-carbethoxyhexafluorobutyryl chloride (4-CB). The analytical method was compared to traditional GC-MS analysis and evaluated with respect to assay chromatography, linearity, sensitivity, precision, accuracy, and reproducibility. The limits of detection were 62.5 ng/mL for MDA and 31.25 ng/mL for AMP, MAMP, MDMA, and MDEA. All of the target analytes were linear to 12,000 ng/mL with the exception of MAMP which was linear to 10,000 ng/mL. The intra-assay precision of a 500 ng/mL multiconstituent control (n=15) ranged from 522.6 to 575.9 ng/mL with a coefficient of variation of less than 3.8%. Authentic human urine specimens (n=187) previously determined to contain the target analytes were re-extracted and analyzed by both FGC-MS and the currently utilized GC-MS method. No significant differences in specimen concentration were observed between these analytical methods. No interferences were seen when the performance of the FGC-MS method was challenged with ephedrine, pseudoephedrine, phenylpropanolamine, and phentermine. When compared to traditional GC-MS analysis, FGC-MS analysis provided a dramatic reduction in retention time for amphetamine (1.8 min vs. 4.12 min). For example, the FGC-MS method reduced overall run time for a batch of 56 specimens from 12.0 h to 7.25 h. This reduction in analysis time makes FGC-MS an attractive alternative to traditional GC-MS by allowing a laboratory greater flexibility in the purchase

  14. Substance use -- amphetamines

    Science.gov (United States)

    ... this case, they are known as street, or recreational drugs, and using them can lead to addiction. This ... especially methamphetamine, have a high chance of getting HIV and hepatitis B and C . This can be ...

  15. Dextroamphetamine and Amphetamine

    Science.gov (United States)

    ... hormone in the body), or feelings of anxiety, tension, or agitation. Your doctor will probably tell you ... blood pressure, an irregular heartbeat, hardening of the arteries, heart or blood vessel disease, or other heart ...

  16. Effects of unilateral 6-OHDA lesions on [3H]-N-propylnorapomorphine binding in striatum ex vivo and vulnerability to amphetamine-evoked dopamine release in rat

    DEFF Research Database (Denmark)

    Palner, Mikael; Kjaerby, Celia; Knudsen, Gitte M

    2011-01-01

    ligands should likewise be fitter than antagonists for detecting responses to denervation in positron emission tomography studies of idiopathic Parkinson's disease. Agonist binding increases in vivo are likely to reflect the composite of a sensitization-like phenomenon, and relatively less competition...... to be more vulnerable to competition from endogenous dopamine than was the antagonist ligand [(11)C]raclopride, measured ex vivo in mouse striatum, and subsequently in multi-tracer PET studies of analogous design. Based on these results, we predicted that prolonged dopamine depletion would result...... in a preferential increase in agonist binding, and a lesser competition from residual dopamine to the agonist binding. To test this hypothesis we used autoradiography to measure [(3)H]NPA and [(3)H]raclopride binding sites in hemi-parkinsonian rats with unilateral 6-OHDA lesions, with and without amphetamine...

  17. Extraction of amphetamines and methylenedioxyamphetamines from urine using a monolithic silica disk-packed spin column and high-performance liquid chromatography-diode array detection.

    Science.gov (United States)

    Namera, Akira; Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Yahata, Midori; Yashiki, Mikio; Nagao, Masataka

    2008-10-24

    To overcome the limitations of solid-phase extraction, we developed a device comprising a spin column packed with octadecyl silane-bonded monolithic silica for extracting amphetamines and methylenedioxyamphetamines from urine. Urine (0.5mL), buffer (0.4mL), and methoxyphenamine (internal standard) were directly put into the preactivated column. The column was centrifuged (3000rpm, 5min) for sample loading and washed. The adsorbed analytes were eluted and analyzed by high-performance liquid chromatography, without evaporation. The results were as follows: linear curves (drug concentrations of 0.2-20microg/mL); correlation coefficients >0.99; detection limit, 0.1microg/mL. The proposed method is not only useful for drugs from biological materials but also highly reproducible for the analysis of these drugs in urine.

  18. Synthesis of polystyrene, poly(styrene/4-vinylpyridine), poly(p-nitrostyrene) and poly(p-aminostyrene)-coated silica and their extraction capabilities for amphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Sun Changmei; Zhang Shuanhong [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Qu Rongjun, E-mail: qurongjun@eyou.com [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China); Sun Tao; Zhang Ying; Zhang Xiang; Song Jingyang [School of Chemistry and Materials Science, Ludong University, Yantai, Shandong 264025 (China)

    2010-11-01

    Several novel organic-inorganic hybrid materials, including polystyrene-coated silica (SG-PS), poly(styrene/4-vinylpyridine)-coated silica (SG-PVP), poly(p-nitrostyrene)-coated silica (SG-PS-NO{sub 2}) and poly(p-aminostyrene)-coated silica (SG-PS-NH{sub 2}), were synthesized in order to improve the extraction methods of harmful stimulants via solid phase extraction. The materials were characterized using infrared spectra (IR), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET) surface area measurement and thermogravimetric analysis (TG). The application of the new materials in solid phase extraction columns to extract methamphetamine revealed that the extraction capability of poly(styrene/4-vinylpyridine)-coated silica is the best among the four materials, which provides novel supporter materials for extracting amphetamine-derived drugs.

  19. A Case of Disulfiram-Induced Psychosis in a Previously Asymptomatic Patient Maintained on Mixed Amphetamine Salts: A Review of the Literature and Possible Pathophysiological Explanations.

    Science.gov (United States)

    Spiegel, David R; McCroskey, Aidan; Puaa, Kapaakea; Meeker, Grant; Hartman, Lauren; Hudson, Joshua; Hung, Yu C

    2016-01-01

    Although perhaps better known as an irreversible aldehyde dehydrogenase inhibitor causing increased acetaldehyde levels after concomitant intake of ethanol, disulfiram or one of its metabolites (diethyldithiocarbamate) also inhibit dopamine β-hydroxylase, an enzyme that converts dopamine to norepinephrine. This mechanism has been advanced as a possible explanation for the development of psychosis, during disulfiram treatment, either in monotherapy or in combination therapy, when interaction-emergent psychosis could be causal. We present a young woman who was taking mixed amphetamine salts for treatment of attention-deficit/hyperactivity disorder and developed a short-lived psychosis after introduction of disulfiram. The psychotic symptoms resolved after discontinuation of both medications, without the use of antipsychotic drugs. We proceed with a review of the literature of disulfiram-induced psychosis and discuss pathophysiological theories that possibly were involved in our patient's phenomenology.

  20. A novel screening method for 64 new psychoactive substances and 5 amphetamines in blood by LC-MS/MS and application to real cases.

    Science.gov (United States)

    Vaiano, Fabio; Busardò, Francesco P; Palumbo, Diego; Kyriakou, Chrystalla; Fioravanti, Alessia; Catalani, Valeria; Mari, Francesco; Bertol, Elisabetta

    2016-09-10

    Identification and quantification of new psychoactive substances (NPS), both in biological and non-biological samples, represent a hard challenge for forensic toxicologists. NPS are increasingly emerging on illegal drug market. Many cases of co-consumption of NPS and other substances have also been reported. Hence, the development of analytical methods aiming at the detection of a broad-spectrum of compounds (NPS and "traditional" drugs) could be helpful. In this paper, a fully validated screening method in blood for the simultaneous detection of 69 substances, including 64 NPS (28 synthetic cannabinoids, 19 synthetic cathinones, 5 phenethylamines, 3 indanes, 2 piperazines, 2 tryptamines, 2 phencyclidine, methoxetamine, ketamine and its metabolite) and 5 amphetamines (amphetamine, methamphetamine, MDMA, MDA, 3,4-methylenedioxy-N-ethylamphetamine - MDEA-) by a dynamic multiple reaction monitoring analysis through liquid chromatography - tandem mass spectrometry (LC-MS/MS) is described. This method is very fast, easy to perform and cheap as it only requires the deproteinization of 200μL of blood sample with acetonitrile. The chromatographic separation is achieved with a C18 column. The analysis is very sensitive, with limits of quantification ranging from 0.1 to 0.5ng/mL. The method is linear from 1 to 100ng/mL and the coefficient of determination (R(2)) was always above 0.9900. Precision and accuracy were acceptable at any quality control level and recovery efficiency range was 72-110%. Matrix effects did not negatively affect the analytical sensitivity. This method was successfully applied to three real cases, allowing identification and quantification of: mephedrone and methamphetamine (post-mortem); ketamine, MDMA and MDA (post-mortem); AB-FUBINACA (ante-mortem).

  1. Inhibition of glycogen synthase kinase-3 by SB 216763 affects acquisition at lower doses than expression of amphetamine-conditioned place preference in rats.

    Science.gov (United States)

    Wickens, Rebekah H; Quartarone, Susan E; Beninger, Richard J

    2016-12-14

    Dopamine (DA) drives incentive learning, whereby neutral stimuli acquire the ability to elicit responses. DA influences the signaling molecule glycogen synthase kinase-3 (GSK3). Inhibition of GSK3 attenuates the development of behavioral sensitization to stimulant drugs and conditioned place preference (CPP), a measure of incentive learning. We examined the role of GSK3 in the nucleus accumbens (NAc) of rats in CPP produced by amphetamine (1.5 mg/kg, i.p. or 20.0 μg/0.5 μl/side intra-NAc) by administering the inhibitor SB 216763 (1.0, 2.0, and 2.5 mg/kg, i.p. or 0.03, 0.30, 3.00, and 5.00 μg/0.5 μl/side intra-NAc) during acquisition or expression. We hypothesized a dose-dependent effect of SB 216763 and that acquisition would be affected by smaller doses than expression. For the systemic groups, 1.0 mg/kg of SB 216763 did not block CPP; 2.0 mg/kg administered in acquisition but not expression blocked CPP; and 2.5 mg/kg administered in either phase blocked CPP. For the central groups, 0.03 μg/0.5 μl/side of SB 216763 prevented acquisition but not expression, whereas larger doses administered in either phase blocked CPP. Thus, systemic or NAc inhibition of GSK3 by SB 216763 during acquisition or expression blocks amphetamine-produced CPP and acquisition is sensitive to lower doses than expression.

  2. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, Akihiro [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nishida, Manami [Hiroshima University Technical Center, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Saito, Takeshi [Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1143 (Japan); Kishiyama, Izumi; Miyazaki, Shota [GL Sciences Inc., Sayamagahara 237-2, Iruma, Saitama 358-0032 (Japan); Murakami, Katsunori [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nagao, Masataka [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Namura, Akira, E-mail: namera@hiroshima-u.ac.jp [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d{sub 5} was used as an internal standard. The linear ranges were 0.01-5.0 {mu}g mL{sup -1} for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 {mu}g mL{sup -1} for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation {>=}0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 {mu}g mL{sup -1} of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio {>=} 3) in urine was 5 ng mL{sup -1} for MA and MDMA and 10 ng mL{sup -1} for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  3. 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis.

    Science.gov (United States)

    Matsumoto, T; Maeno, Y; Kato, H; Seko-Nakamura, Y; Monma-Ohtaki, J; Ishiba, A; Nagao, M; Aoki, Y

    2014-08-01

    Using in vivo microdialysis, a comparative study was conducted to examine the effects of amphetamine-related compounds (methamphetamine, MAP; 3,4-methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p-methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5-trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were assayed using HPLC equipped with electrochemical detector following i.p. administration with each drug at a dose of 5 mg/kg. MAP was found to drastically and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA, PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased 5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in levels of both monoamines. We observed that the potent DA-releasing action of MAP was remarkably decreased by introduction of methoxy or methylthio group at the para position (MAP vs. PMMA or 4-MTA), but introduction of two additional adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely affected the activity of both MAO enzymes as well as extracellular levels of 5-HT and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to PMMA, a typical empathogen; these findings therefore could be helpful in clarifying the psychopharmacological properties of amphetamine-related, empathogenic designer drugs.

  4. Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LC-ESI-MS/MS. Application to the determination of MDMA after low ecstasy intake.

    Science.gov (United States)

    Chèze, Marjorie; Deveaux, Marc; Martin, Claire; Lhermitte, Michel; Pépin, Gilbert

    2007-08-06

    A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C(18) 5 microm, 2.1 mm x 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 degrees C in NaOH 1M before liquid-liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was urine; in the range 5-500 pg/mg for MA, MDMA, MDEA and MBDB, and 20-500 pg/mg for AP and MDA. Inter-day precisions were urine at 1 and 50 ng/mL and urine was collected a few hours after (T+12h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D+8) and scalp hair at day 60 (D+60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.

  5. Stereoselective method development and validation for determination of concentrations of amphetamine-type stimulants and metabolites in human urine using a simultaneous extraction-chiral derivatization approach.

    Science.gov (United States)

    Wan Raihana, W A; Gan, S H; Tan, S C

    2011-01-01

    Amphetamine-type stimulants (ATS) are a group of chiral amine drugs which are commonly abused for their sympathomimetic and stimulant properties. ATS are extensively metabolised by hepatic cytochrome P450 enzymes. As metabolism of ATS has been shown to be highly stereospecific, stereoselective analytical methods are essential for the quantitative determination of ATS concentrations for both in vivo and in vitro studies of ATS metabolism. This paper describes a new stereoselective method for the simultaneous determination of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-hydroxymethamphetamine (HHMA) and 3,4-hydroxyamphetamine (HHA) in human urine samples validated according to the United States Food and Drug Administration guidelines. In this method, analytes are simultaneously extracted and derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-MTPCl) as the chiral derivatization reagent. Following this, the analytes were subjected to a second derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) which targets the hydroxyl groups present in HMMA, HMA, HHMA and HHA. The derivatized analytes were separated and quantified using gas chromatography-mass spectrometry (GC-MS). The method was evaluated according to the established guidelines for specificity, linearity, precision, accuracy, recovery and stability using a five-day protocol. Intra-day precision ranged from 0.89 to 11.23% RSD whereas inter-day precision was between 1.03 and 12.95% RSD. Accuracy values for the analytes ranged from -5.29% to 13.75%. Limits of quantitation were 10 μg/L for AM, MA, MDMA, HMA and HMMA and 2μg/L for MDA, HMA and HHA. Recoveries and stability values were also within accepted values. The method was applied to authentic ATS-positive samples.

  6. Cross-reactivities of various phenethylamine-type designer drugs to immunoassays for amphetamines, with special attention to the evaluation of the one-step urine drug test Instant-View™, and the Emit® assays for use in drug enforcement.

    Science.gov (United States)

    Nakanishi, Keiko; Miki, Akihiro; Zaitsu, Kei; Kamata, Hiroe; Shima, Noriaki; Kamata, Tooru; Katagi, Munehiro; Tatsuno, Michiaki; Tsuchihashi, Hitoshi; Suzuki, Koichi

    2012-04-10

    Cross-reactivities of 76 kinds of phenethylamine-type designer drugs and related compounds to the urine drug tests Instant-View ™ (IV) (the Methamphetamine (MA) test, the Amphetamine 300 test, and the MDMA test) have been investigated. An on-site urine test kit consisting of these three IV tests has been evaluated for the on-site screening of MA users, and the kit has been found to have satisfactory specificity for drug enforcement purposes by separately detecting both MA and its metabolite amphetamine. The cross-reactivity profiles of Emit(®) II Plus Amphetamines Assay, Emit(®) II Plus Ecstasy assay, and Emit(®) d.a.u.(®) Amphetamine Class assay have also been investigated and discussed.

  7. Effect of amphetamine on eukaryotic translation elongation factor 2 in the frontal cortex of mice%苯丙胺对小鼠额叶皮质真核翻译延伸因子2的影响

    Institute of Scientific and Technical Information of China (English)

    刘钦; 曾文钦; 程亚涛; 姚前尹

    2015-01-01

    Objective To explore the effect of amphetamine on eukaryotic translation elongation factor 2 (eEF2) in the frontal cortex of mice.Methods Male C57BL/6 mice were randomly divided into normal control group (n=10),saline group (n=10) and amphetamine treatment group (n=40);the amphetamine treatment group was divided into 1,7,14 and 28 d subgroups (n=10).Mice in the amphetamine treatment group were treated with amphetamine 2 mg/(kg· d) via intraperitoneal injection;those in the saline group received a same dose of saline,while those in the normal control group received no treatment.Autonomous behavior activities were tested during establishing amphetamine models.Immunohistochemistry and Westem blotting were used to identify the eEF2 expressions.Results Behaviour test showed that total moving distance,average speed,maximum speed,moving fast time/total time in the 7,14 and 28 d amphetamine treatment subgroups were significantly increased as compared with those in the normal control group and saline group (P<0.05).Immumohistochemical staining indicated that the grey values of eEF2-positive inummoreactive products in the amphetamine treatment group were significantly lower than those in the normal control group and saline group (P<0.05);those of eEF2-positive inummoreactive products in 14 and 28 d amphetamine treatment subgroups were significantly lower than those in 1 and 7 d amphetamine treatment subgroups (P<0.05).Western blotting showed that eEF2 protein expression in the frontal cortex was significantly elevated in the amphetamine treatment group as compared with that in the other two groups (P<0.05);the eEF2 expression in the amphetamine treatment group increased with time prolonging within 28 days after establishment of models.Conclusion Amphetamine can induce increased eEF2 expression in the frontal cortex of mice.%目的 观察苯丙胺干预后小鼠额叶皮质内真核翻译延伸因子2(eEF2)的表达情况.方法 雄性C57BL/6小鼠按随机数

  8. Phentermine interference and high L-methamphetamine concentration problems in GC-EI-MS SIM Analyses of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride-derivatized amphetamines and methamphetamines†.

    Science.gov (United States)

    Hamilton, Theron J; Qui, Harry Z; Dozier, Katherine V R; Fuller, Zachary J

    2014-09-01

    In order to achieve chromatographic separation, urine samples shown to be initially positive for amphetamines and methamphetamines in US Department of Defense immunoassays are derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-(-)-MTPA) prior to gas chromatography-electron impact-mass spectrometry (GC-EI-MS) analysis. Phentermine, a member of the phenethylamine class of drugs and a common appetite suppressant, interferes with GC-EI-MS assays of R-(-)-MTPA-derivatized d-amphetamine, degrading the chromatography of the internal standard and analyte ions and skewing concentration calculations. Additionally, when specimens with high concentrations of l-methamphetamine are derivatized with R-(-)-MTPA, signal peaks have the potential to be misidentified by integration software as d-methamphetamine. We have found that replacing R-(-) MTPA with (S)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride reduces phentermine interference problems related to internal standard chromatography, reduces the possibility of concentrated l-methamphetamine peaks being misidentified by integration software, improves resolution of d-methamphetamine in the presence of high l-methamphetamine concentrations, and is a cost-neutral change that can be applied to current amphetamines GC-EI-MS methods without the need for method modification.

  9. Effects of intra-amygdala R(+) 7-OH-DPAT on intra-accumbens d-amphetamine-associated learning. I. Pavlovian conditioning.

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    Hitchcott, P K; Phillips, G D

    1998-12-01

    We have previously obtained evidence that the mesoamygdaloid dopamine projection modulates the acquisition of a conditioned response (CR) elicited by presentation of a conditioned stimulus (CS) predicting the availability of a natural (sucrose) reward. This property was found to be dependent upon D3, but not D1 or D2, dopamine receptor activation. The aim of the present study was to determine whether the mesoamygdaloid dopamine projection is similarly involved in the acquisition of a drug-associated CR. Thus, two groups of rats with guide cannulae aimed at the nucleus accumbens and amygdala were trained using a Pavlovian conditioning procedure in which an initially neutral CS was paired with a computer-controlled, bilateral intraaccumbens infusion of d-amphetamine (the unconditioned stimulus: US). Conditioning sessions were conducted in standard operant chambers, with each session consisting of a single CS-US trial. For one group of rats, CS presentation was positively correlated with the drug US (Paired group), while for the second group CS and US presentations were negatively correlated (Unpaired group). During training, locomotor activity was recorded and was utilised as the measure both of the unconditioned (UR) and conditioned response (CR). A within-subjects design was utilised to investigate the effect of post-session bilateral intraamygdala administration of R(+) 7-OH-DPAT on the development of the drug-associated CR. Hence, both Paired and Unpaired groups were exposed to two different CSs which were presented on alternate sessions. Post-session bilateral intra-amygdala administration of R(+) 7-OH-DPAT (10 nmol) followed sessions in which one CS was presented, while intra-amygdala vehicle followed sessions in which the alternate CS was presented. The development of a CR occurred only in the presence of a CS that had been positively correlated with presentation of the drug US. Post-session, intra-amygdala administration of R(+) 7-OH-DPAT enhanced the

  10. High-throughput analysis of amphetamines in blood and urine with online solid-phase extraction-liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fernández, María del Mar Ramírez; Wille, Sarah M R; Samyn, Nele; Wood, Michelle; López-Rivadulla, Manuel; De Boeck, Gert

    2009-01-01

    An automated online solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS-MS) method for the analysis of amphetamines in blood and urine was developed and validated. Chromatographic separation was achieved on a Nucleodur Sphinx RP column with an LC gradient (a mixture of 10 mM ammonium formate buffer and acetonitrile), ensuring the elution of amphetamine, methamphetamine, MDMA, MDA, MDEA, PMA, and ephedrine within 11 min. The method was fully validated, according to international guidelines, using only 100 and 50 microL of blood and urine, respectively. The method showed an excellent intra- and interassay precision (relative standard deviation 0.99, 2.5-400 microg/L for blood and 25-1000 microg/L for urine). Limits of quantification were determined to be 2.5 and 25 microg/L for blood and urine, respectively. Limits of detection ranged from 0.05 to 0.5 microg/L for blood and 0.25 to 2.5 microg/L for urine, depending on the compound. Furthermore, the analytes and the processed samples were demonstrated to be stable (in the autosampler for at least 72 h and after three freeze/thaw cycles), and no disturbing matrix effects were observed for all compounds. Moreover, no carryover was observed after the analysis of high concentration samples (15,000 microg/L). The method was subsequently applied to authentic blood and urine samples obtained from forensic cases, which covered a broad range of concentrations. The validation results and actual sample analyses demonstrated that this method is rugged, precise, accurate, and well-suited for routine analysis as more than 72 samples are analyzed non-stop in 24 h with minimum sample handling. The combination of the high-throughput online SPE and the well-known sensitivity and selectivity assured by MS-MS resulted in the elimination of the bottleneck associated with the sample preparation requirements and provided increased sensitivity, accuracy, and precision.

  11. Uso de álcool e anfetaminas entre caminhoneiros de estrada Alcohol and amphetamines use among long-distance truck drivers

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    Eurípedes Costa do Nascimento

    2007-04-01

    Full Text Available O objetivo do estudo foi analisar a incidência do uso de álcool e anfetaminas entre caminhoneiros de estrada. Foram estudados 91 sujeitos, abordados em um posto de combustíveis em Passos, MG, em novembro de 2005. Os dados dos participantes foram obtidos por meio de um questionário contendo 19 questões de múltipla escolha. Utilizou-se para a análise dos dados estatística descritiva, teste do qui-quadrado e o coeficiente de correlação de Cramér. Os resultados indicaram que 66% dos caminhoneiros usavam anfetaminas durante os percursos de viagens, principalmente em postos de combustíveis (54% à beira das rodovias. O álcool era utilizado por 91% deles, dos quais 43% consumiam a bebida nos postos de combustíveis. Concluiu-se que há a necessidade de campanhas preventivas e informativas voltadas para esta categoria profissional nos postos de combustíveis e empresas de transportes, alertando sobre os riscos de ingestão dessas substâncias no período de trabalho.The purpose of the study was to assess the incidence of alcohol and amphetamine use among long-distance truck drivers. There were studied 91 truck drivers at the gas station in Passos, Southeastern Brazil, in November 2005. Data was collected using a questionnaire comprising 19 multiple choice questions. Descriptive statistics, Chi-square test and Cramér's correlation coefficient were used for data analysis. The results indicated that 66% of the long-distance truck drivers used amphetamines during their travels, mainly at gas stations along the highways (54%. Alcohol was consumed by 91% of them and 43% of them consumed it at gas stations. It is concluded that there is a need of preventive and education campaigns targeting this occupation category at gas stations and transportation companies, focusing on the risks of these substances use during working hours.

  12. Participation of ghrelin signalling in the reciprocal regulation of hypothalamic NPY/POMC-mediated appetite control in amphetamine-treated rats.

    Science.gov (United States)

    Yu, Ching-Han; Chu, Shu-Chen; Chen, Pei-Ni; Hsieh, Yih-Shou; Kuo, Dong-Yih

    2017-02-14

    Hypothalamic neuropeptide Y (NPY) and proopiomelanocortin (POMC) have been documented to participate in amphetamine (AMPH)-induced appetite suppression. This study investigated whether ghrelin signalling is associated with changes in NPY/POMC-mediated appetite control. Rats were given AMPH daily for four days, and changes in food intake, body weight, plasma ghrelin, hypothalamic NPY, melanocortin 3 receptor (MC3R), ghrelin O-acyltransferase (GOAT), acyl ghrelin (AG) and ghrelin receptor (GHSR1a) were examined and compared. Food intake, body weight and NPY expression decreased, while MC3R expression increased and expressed reciprocally to NPY expression during AMPH treatment. Plasma ghrelin and hypothalamic AG/GOAT/GHSR1a expression decreased on Day 1 and Day 2, which was associated with the positive energy metabolism, and returned to normal levels on Day 3 and Day 4, which was associated with the negative energy metabolism; this expression pattern was similar to that of NPY. Infusion with a GHSR1a antagonist or an NPY antisense into the brain enhanced the decrease in NPY and AG/GOAT/GHSR1a expression and the increase in MC3R expression compared to the AMPH-treated group. Peripheral ghrelin and the central ghrelin system participated in the regulation in AMPH-induced appetite control. These results shed light on the involvement of ghrelin signalling in reciprocal regulation of NPY/POMC-mediated appetite control and may prove useful for the development of anti-obesity drugs.

  13. Amphetamine-induced sensitization has little effect on multiple learning paradigms and fails to rescue mice with a striatal learning defect.

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    Kiara C Eldred

    Full Text Available Behavioral sensitization to psychostimulants such as amphetamine (AMPH is associated with synaptic modifications that are thought to underlie learning and memory. Because AMPH enhances extracellular dopamine in the striatum where dopamine and glutamate signaling are essential for learning, one might expect that the molecular and morphological changes that occur in the striatum in response to AMPH, including changes in synaptic plasticity, would affect learning. To ascertain whether AMPH sensitization affects learning, we tested wild-type mice and mice lacking NMDA receptor signaling in striatal medium spiny neurons in several different learning tests (motor learning, Pavlovian association, U-maze escape test with strategy shifting with or without prior sensitization to AMPH. Prior sensitization had minimal effect on learning in any of these paradigms in wild-type mice and failed to restore learning in mutant mice, despite the fact that the mutant mice became sensitized by the AMPH treatment. We conclude that the changes in synaptic plasticity and many other signaling events that occur in response to AMPH sensitization are dissociable from those involved in learning the tasks used in our experiments.

  14. Cortical Dopamine Transmission as Measured with the [11C]FLB 457 - Amphetamine PET Imaging Paradigm Is Not Influenced by COMT Genotype.

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    Rajesh Narendran

    Full Text Available Basic investigations link a Val158Met polymorphism (rs4680 in the catechol-O-methyltransferase (COMT gene to not only its enzymatic activity, but also to its dopaminergic tone in the prefrontal cortex. Previous PET studies have documented the relationship between COMT Val158Met polymorphism and D1 and D2/3 receptor binding potential (BP, and interpreted them in terms of dopaminergic tone. The use of baseline dopamine D1 and D2/3 receptor binding potential (BPND as a proxy for dopaminergic tone is problematic because they reflect both endogenous dopamine levels (a change in radiotracer's apparent affinity and receptor density. In this analysis of 31 healthy controls genotyped for the Val158Met polymorphism (Val/Val, Val/Met, and Met/Met, we used amphetamine-induced displacement of [11C]FLB 457 as a direct measure of dopamine release. Our analysis failed to show a relationship between COMT genotype status and prefrontal cortical dopamine release. COMT genotype was also not predictive of baseline dopamine D2/3 receptor BPND.

  15. Separation mechanism of chiral impurities, ephedrine and pseudoephedrine, found in amphetamine-type substances using achiral modifiers in the gas phase.

    Science.gov (United States)

    Holness, Howard K; Jamal, Adeel; Mebel, Alexander; Almirall, José R

    2012-11-01

    A new mechanism is proposed that describes the gas-phase separation of chiral molecules found in amphetamine-type substances (ATS) by the use of high-resolution ion mobility spectrometry (IMS). Straight-chain achiral alcohols of increasing carbon chain length, from methanol to n-octanol, are used as drift gas modifiers in IMS to highlight the mechanism proposed for gas-phase separations of these chiral molecules. The results suggest the possibility of using these achiral modifiers to separate the chiral molecules (R,S) and (S,R)-ephedrine and (S,S) and (R,R)-pseudoephedrine which contain an internal hydroxyl group at the first chiral center and an amino group at the other chiral center. Ionization was achieved with an electrospray source, the ions were introduced into an IMS with a resolving power of 80, and the resulting ion clusters were characterized with a coupled quadrupole mass spectrometer detector. A complementary computational study conducted at the density functional B3LYP/6-31g level of theory for the electronic structure of the analyte-modifier clusters was also performed, and showed either "bridged" or "independent" binding. The combined experimental and simulation data support the proposed mechanism for gas-phase chiral separations using achiral modifiers in the gas phase, thus enhancing the potential to conduct fast chiral separations with relative ease and efficiency.

  16. Female sex workers who use amphetamine-type stimulants (ATS) in three cities of Vietnam: use and sexual risks related to HIV/AIDS.

    Science.gov (United States)

    Ho, Hien Thi; Le, Giang Minh; Dinh, Thuy Thanh

    2013-01-01

    Early evidence shows that amphetamine-type stimulant (ATS) use has been rapidly increasing in Vietnam. Female sex workers (FSWs) who use ATSs have increased sexual risks for HIV infection. This paper presents qualitative data from a mixed-method study conducted from 2010 to 2011 that aimed to explore the use of ATS among FSWs in three major cities and to identify HIV-related sexual risks among this group. A total of 37 in-depth interviews were conducted, and thematic analysis was performed using NVIVO 8.0 software. Study participants reported that they perceive ATS to be more 'stylish', 'higher class' and much less 'addictive' than heroin. The study highlights multiple sexual risks among this group, including having prolonged sex; sex with multiple simultaneous partners or clients; lack of negotiation for safe sex; increased likelihood of group sex in the context of drug pooling and extended drug and sexual network; as well as unprotected sex. There is an urgent need to promote contextually appropriate interventions to reduce the HIV-related sexual risks among this group.

  17. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  18. Online extraction LC-MS/MS method for the simultaneous quantitative confirmation of urine drugs of abuse and metabolites: amphetamines, opiates, cocaine, cannabis, benzodiazepines and methadone.

    Science.gov (United States)

    de Jager, Andrew D; Bailey, Neville L

    2011-09-01

    A rapid LC-MS/MS method for confirmatory testing of five major categories of drugs of abuse (amphetamine-type substances, opiates, cocaine, cannabis metabolites and benzodiazepines) in urine has been developed. All drugs of abuse mandated by the Australian/New Zealand Standard AS/NZS 4308:2008 are quantified in a single chromatographic run. Urine samples are diluted with a mixture of isotope labelled internal standards. An on-line trap-and-flush approach, followed by LC-ESI-MS/MS has been successfully used to process samples in a functioning drugs of abuse laboratory. Following injection of diluted urine samples, compounds retained on the trap cartridge are flushed onto a reverse-phase C18 HPLC column (5-μm particle size) with embedded hydrophylic functionality. A total chromatographic run-time of 15 min is required for adequate resolution. Automated quantitation software algorithms have been developed in-house using XML scripting to partially automate the identification of positive samples, taking into account ion ratio (IR) and retention times (Rt). The sensitivity of the assay was found to be adequate for the quantitation of drugs in urine at and below the confirmation cut-off concentrations prescribed by AS/NZS 4308:2008.

  19. Expression of Cocaine and Amphetamine Regulated Transcript (CART) in the Porcine Intramural Neurons of Stomach in the Course of Experimentally Induced Diabetes Mellitus.

    Science.gov (United States)

    Bulc, Michał; Gonkowski, Sławomir; Całka, Jarosław

    2015-11-01

    In the present study, the effect of streptozotocin-induced diabetes on the cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) enteric nervous structures was investigated within the porcine stomach. To induce diabetes, the pigs were administered intravenously streptozotocin at a dose of 150 mg/kg of body weight. A significant decrease of the number of CART-LI perikarya was observed in the myenteric plexus of the gastric antrum, corpus, and pylorus in the experimental group. In contrast, submucous plexus was devoid of CART-positive neuronal cells both in control and experimental animals. In the control group, the highest densities of CART-LI nerve fibers were observed in the circular muscle layer of antrum and slightly less nerve fibers were present in the muscle layer of corpus and pylorus. In turn, submucous layer of all studied stomach regions revealed relatively smaller number of CART-positive nerve fibers. Diabetes caused statistically significant decrease in the expression of CART-LI nerve fibers only in the antrum circular muscle layer. Also, no changes in the CART-like immunoreactivity in the intraganglionic nerve fibers were observed. The obtained results suggest that acute hyperglycemia produced significant reduction of the CART expression in enteric perikarya throughout entire stomach as well as decrease of density the CART-LI fibers in circular muscle layer of the antrum. Additionally, we suggest that CART might be involved in the regulation of stomach function especially in the gastric motility.

  20. Leptin-Induced CART (Cocaine- and Amphetamine-Regulated Transcript) Is a Novel Intraovarian Mediator of Obesity-Related Infertility in Females.

    Science.gov (United States)

    Ma, Xiaoting; Hayes, Emily; Prizant, Hen; Srivastava, Rajesh K; Hammes, Stephen R; Sen, Aritro

    2016-03-01

    Obesity is considered detrimental to women's reproductive health. Although most of the attention has been focused on the effects of obesity on hypothalamic function, studies suggest a multifactorial impact. In fact, obesity is associated with reduced fecundity even in women with regular cycles, indicating that there may be local ovarian effects modulating fertility. Here we describe a novel mechanism for leptin actions directly in the ovary that may account for some of the negative effects of obesity on ovarian function. We find that normal cycling, obese, hyperleptinemic mice fed with a high-fat diet are subfertile and ovulate fewer oocytes compared with animals fed with a normal diet. Importantly, we show that leptin induces expression of the neuropeptide cocaine- and amphetamine-regulated transcript (CART) in the granulosa cells (GCs) of ovarian follicles both in vitro and in vivo. CART then negatively affects intracellular cAMP levels, MAPK signaling, and aromatase mRNA expression, which leads to lower estradiol synthesis in GCs and altered ovarian folliculogenesis. Finally, in human samples from patients undergoing in vitro fertilization, we show a significant positive correlation between patient body mass index, CART mRNA expression in GCs, and CART peptide levels in follicular fluid. These observations suggest that, under obese conditions, CART acts as a local mediator of leptin in the ovary to cause ovarian dysfunction and reduced fertility.

  1. A first-principles study on the adsorption behavior of amphetamine on pristine, P- and Al-doped B12N12 nano-cages

    Science.gov (United States)

    Bahrami, Aidin; Seidi, Shahram; Baheri, Tahmineh; Aghamohammadi, Mohammad

    2013-12-01

    The first-principles computations using density functional theory (DFT) calculations at the M062X/6-311++G** level have been applied to scrutinize the adsorption behavior of amphetamine (AMP) molecule on the external surface of pristine, P- and Al-doped B12N12 nano-cages. In order to gain insight into the binding features of pristine and doped B12N12 complexes as adsorbent with AMP, the structural and electronic parameters as well as the Atoms in Molecules (AIM) properties were examined. The results showed that AMP prefers to adsorb via its nitrogen atom on the Lewis acid sites of B and Al atoms of the nano-cages. On the basis of calculated density of states, the interaction of AMP with the external wall of B12N12 leads to the remarkable differences in their conductivities. Presence of polar solvent increases the AMP adsorption on the nano-cage. In addition, AIM based analyses indicated an electrostatic nature for N-B interaction in Amph-B12N12 and partial covalent for N-Al in AMP-B11AlN12. Based on calculated results, the B12N12 and B11AlN12 nano-cages are expected to be a potential efficient adsorbent as well as sensors for adsorption of AMP in environmental systems.

  2. Comparative distribution of cocaine- and amphetamine-regulated transcript (CART) in the hypothalamus of the capuchin monkey (Cebus apella) and the common marmoset (Callithrix jacchus).

    Science.gov (United States)

    Cavalcante, Judney Cley; Cândido, Paulo Laino; Sita, Luciane Valéria; do Nascimento, Expedito Silva; Cavalcante, Jeferson de Souza; de Oliveira Costa, Miriam Stela Maris; Bittencourt, Jackson Cioni; Elias, Carol Fuzeti

    2011-11-24

    Cocaine- and amphetamine-regulated transcript (CART) is widely distributed in the brain of many species. In the hypothalamus, CART neurotransmission has been implicated in diverse functions including energy balance, stress response, and temperature and endocrine regulation. Although some studies have been performed in primates, very little is known about the distribution of CART neurons in New World monkeys. New World monkeys are good models for systems neuroscience, as some species have evolved several behavioral and anatomical characteristics shared with humans, including diurnal and social habits, intense maternal care, complex manipulative abilities and well-developed frontal cortices. In the present study, we assessed the distribution of CART mRNA and peptide in the hypothalamus of the capuchin monkey (Cebus apella) and the common marmoset (Callithrix jacchus). We found that the distribution of hypothalamic CART neurons in these monkeys is similar to what has been described for rodents and humans, but some relevant differences were noticed. Only in capuchin monkeys CART neurons were observed in the suprachiasmatic and the intercalatus nuclei, whereas only in marmoset CART neurons were observed in the dorsal anterior nucleus. We also found that the only in marmoset displayed CART neurons in the periventricular preoptic nucleus and in an area seemingly comprising the premammillary nucleus. These hypothalamic sites are both well defined in rodents but poorly defined in humans. Our findings indicate that CART expression in hypothalamic neurons is conserved across species but the identified differences suggest that CART is also involved in the control of species-specific related functions.

  3. PREVALENCIA Y FACTORES ASOCIADOS AL CONSUMO DE ANFETAMINAS, EN ESTUDIANTES DEL PROGRAMA DE MEDICINA DE LA UNIVERSIDAD DE MANIZALES (COLOMBIA, 2010 The prevalence and factors associated with amphetamines use by medical students from the Universidad de Manizales (Colombia, 2010

    Directory of Open Access Journals (Sweden)

    Laura Barón

    2011-09-01

    Full Text Available Antecedentes. Un estudio previo realizado en la Universidad de Manizales midió el consumo de anfetaminas para mejorar rendimiento académico y demostró que el 42,3% de los estudiantes de Medicina consumían anfetaminas con este propósito. Objetivo. Confirmar este resultado e indagar por los factores asociados al consumo de anfetaminas, en estos estudiantes. Materiales y métodos. Se realizó un estudio de corte transversal en el que participaron estudiantes del Programa de Medicina de la Universidad de Manizales. La población fue de 615 mediante un muestreo probabilístico se seleccionaron 234 estudiantes. El instrumento utilizado fue una encuesta anónima que permitió identificar el consumo de estimulantes y factores de riesgo asociados. Resultados. El 51,9% (lc95%:44,9%-58,95 de la muestra aseveró haber consumido anfetaminas para mejorar rendimiento académico; de estos el 70,9% refirieron haber logrado el objetivo. No se encontró relación con factores de riesgo clásicos como ansiedad, depresión o funcionalidad familiar. El 87,9% no consumía estimulantes previo al ingreso al programa. Los semestres VI, VII, VIII y IX mostraron un mayor índice de consumo de: 73,3%, 60%, 68,8% y 57,7% respectivamente. Entre las razones de consumo se resaltan motivos académicos 32,5% y preservar estado de vigilia 18,7%. El 65,8% consumen bebidas alcohólicas. Conclusiones. El consumo de anfetaminas para mejorar rendimiento académico en los estudiantes del Programa de Medicina de la Universidad de Manizales es realmente alarmante. Se hace necesario intervenir en la causa y plantear soluciones para de esta manera, impactar los índices de consumo.Background. A prior study carried out in the Universidad de Manizales measured amphetamine consumption aimed at improving academic performance and revealed that 42.3% of medical students consumed amphetamines for such purpose. Objective. Confirming the aforementioned result and investigating the factors

  4. Wipe sampling of amphetamine-type stimulants and recreational drugs on selected household surfaces with analysis by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J.M.; Boles, Jeffrey O., E-mail: jboles@tntech.edu

    2013-06-15

    Highlights: • Degree of sorption of eight drugs on eleven countertop surfaces was investigated. • Surface composition, volatility and solvent composition played a role in sorption. • Solvent-dependent migration was a key factor of consideration during remediation. • SPME-assisted volatility studies provided evidence for varying degrees of recovery. • Rapid three minute UPLC-QTOF method was developed to quantify the eight compounds. -- Abstract: Sorption characteristics of eight drugs related to recreational and clandestine activity—amphetamine, cocaine, heroin, N-formyl amphetamine, N-formyl methamphetamine, methamphetamine, 3, 4-methylenedioxymethamphetamine (MDMA), and pseudoephedrine—were evaluated on selected kitchen countertop surfaces. Methanol-dampened Whatman™ 40 filter paper wipes were used to collect samples from eleven surfaces including alkyd resin, ceramic tiles, glass, granite, laminate, limestone, marble, quartz compac, quartz real, soap stone, and stainless steel. The filter paper wipes were analyzed by a rapid three-minute UPLC-QTOF method, following ammonium acetate buffer (pH 5.8–6.2) extraction. The average percentage recoveries after 15 h of exposure to the surface materials tested, was found to be highest for cocaine and MDMA and lowest for amphetamine and methamphetamine. Among the eleven countertop surfaces, overall recoveries for marble were observed to be the least, whereas soapstone, quartz compac and stainless steel were among the highest. Scanning electron microscopic images of the surfaces provided a unique view of surface irregularities that potentially influenced drug recovery. Aging, migration, solvent composition, and volatility were examined. The variation in recovery of drugs was attributed to four key factors: compound volatility, surface composition, surface—compound interaction, and solvent composition.

  5. A hybrid liquid chromatography-mass spectrometry strategy in a forensic laboratory for opioid, cocaine and amphetamine classes in human urine using a hybrid linear ion trap-triple quadrupole mass spectrometer.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam; Tierney, Julie; Nangle, Michael

    2010-10-29

    A rapid method has been developed to analyse morphine, codeine, morphine-3-glucuronide, 6-monoacetylmorphine, cocaine, benzoylegonine, buprenorphine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and methadone in human urine. Urine samples were diluted with methanol:water (1:1, v/v) and sample aliquots were analysed by hybrid linear ion trap-triple quadrupole mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35±15 in positive mode and MRM ratios. The method was validated in urine, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra and deuterated analytes were used as internal standards for quantitation. The reporting level was 0.05 μg mL(-1) for the range of analytes tested. The regression coefficients (r(2)) for the calibration curves (0-4 μg mL(-1)) in the study were ≥0.98. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines and amphetamines in criminal samples from crime offenders, abusers or victims in the Republic of Ireland. To the best of our knowledge there are no hybrid LC-MS applications using MRM mode and product ion spectra in the linear ion trap mode for opioids, cocaines or amphetamines with validation data in urine.

  6. ELECTROPHYSIOLOGICAL CHARACTERISTICS OF PARAVENTRICULAR THALAMIC (PVT NEURONS IN RESPONSE TO CHRONIC COCAINE EXPOSURE: EFFECTS OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT (CART

    Directory of Open Access Journals (Sweden)

    Jiann Wei eYeoh

    2014-08-01

    Full Text Available Recent work has established that the paraventricular thalamus (PVT is a central node in the brain reward-seeking pathway. This role is likely mediated in part through the dense projections to the PVT from hypothalamic peptide transmitter systems such as orexin, and cocaine- and amphetamine-regulated transcript (CART, both of which play key roles in drug-seeking behaviour. Consistent with this proposition, we previously found that inactivation of the PVT or infusions of CART into the PVT suppressed drug-seeking behaviour in an animal model of contingent cocaine self-administration. Despite this work, very few studies have assessed the basic physiological properties of PVT neurons and how these parameters are altered by exposure to drugs such as cocaine. We set out to address these questions by employing an electrophysiological approach to record from anterior PVT (aPVT neurons from cocaine-treated and control animals. First, we determined the excitability of aPVT neurons by injecting a series of depolarizing current steps and characterizing the resulting action potential (AP discharge properties. Second, we investigated the effects of CART on excitatory synaptic inputs to aPVT neurons. We found that the majority of aPVT neurons exhibited tonic firing (TF, and initial bursting (IB consistent with previous studies. However, we also identified PVT neurons that exhibited delayed firing (DF, single spiking (SS and reluctant firing (RF. Interestingly, cocaine exposure shifted the proportion of aPVT neurons that exhibited TF. Further, application of CART suppressed excitatory synaptic drive to PVT. This finding is consistent with our previous behavioural data, which showed that CART signaling in the PVT negatively regulates drug-seeking behaviour. Together, these studies support previous anatomical evidence that the PVT can integrate reward-relevant information and provides a putative mechanism through which drugs of abuse can dysregulate this system in

  7. An amphipathic alpha-helix in the prodomain of cocaine and amphetamine regulated transcript peptide precursor serves as its sorting signal to the regulated secretory pathway.

    Directory of Open Access Journals (Sweden)

    Elías H Blanco

    Full Text Available Cocaine and Amphetamine Regulated Transcript (CART peptides are anorexigenic neuropeptides. The L34F mutation in human CART peptide precursor (proCART has been linked to obesity (Yanik et al. Endocrinology 147: 39, 2006. Decrease in CART peptide levels in individuals carrying the L34F mutation was attributed to proCART subcellular missorting. We studied proCART features required to enter the regulated secretory pathway. The subcellular localization and the secretion mode of monomeric EGFP fused to the full-length or truncated forms of human proCART transiently transfected in PC12 cells were analyzed. Our results showed that the N-terminal 1-41 fragment of proCART was necessary and sufficient to sort proCART to the regulated secretory pathway. In silico modeling predicted an alpha-helix structure located between residues 24-37 of proCART. Helical wheel projection of proCART alpha-helix showed an amphipathic configuration. The L34F mutation does not modify the amphipathicity of proCART alpha-helix and consistently proCARTL34F was efficiently sorted to the regulated secretory pathway. However, four additional mutations to proCARTL34F that reduced its alpha-helix amphipathicity resulted in the missorting of the mutated proCART toward the constitutive secretory pathway. These findings show that an amphipathic alpha-helix is a key cis-structure for the proCART sorting mechanism. In addition, our results indicate that the association between L34F mutation and obesity is not explained by proCART missorting.

  8. Corticotropin-releasing hormone (CRH) stimulates cocaine- and amphetamine-regulated transcript gene (CART1) expression through CRH type 1 receptor (CRHR1) in chicken anterior pituitary.

    Science.gov (United States)

    Mo, Chunheng; Cai, Guoqing; Huang, Long; Deng, Qiuyang; Lin, Dongliang; Cui, Lin; Wang, Yajun; Li, Juan

    2015-12-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide(s) is generally viewed as neuropeptide(s) and can control food intake in vertebrates, however, our recent study revealed that CART1 peptide is predominantly expressed in chicken anterior pituitary, suggesting that cCART1 peptide is a novel pituitary hormone in chickens and its expression is likely controlled by hypothalamic factor(s). To test this hypothesis, in this study, we examined the spatial expression of CART1 in chicken anterior pituitary and investigated the effect of hypothalamic corticotropin-releasing hormone (CRH) on pituitary cCART1 expression. The results showed that: 1) CART1 is expressed in both caudal and cephalic lobes of chicken anterior pituitary, revealed by quantitative real-time PCR (qPCR), western blot and immuno-histochemical staining; 2) CRH potently stimulates cCART1 mRNA expression in cultured chick pituitary cells, as examined by qPCR, and this effect is blocked by CP154526 (and not K41498), an antagonist specific for chicken CRH type I receptor (cCRHR1), suggesting that cCRHR1 expressed on corticotrophs mediates this action; 3) the stimulatory effect of CRH on pituitary cCART1 expression is inhibited by pharmacological drugs targeting the intracellular AC/cAMP/PKA, PLC/IP3/Ca(2+), and MEK/ERK signaling pathways. This finding, together with the functional coupling of these signaling pathways to cCRHR1 expressed in CHO cells demonstrated by luciferase reporter assay systems, indicates that these intracellular signaling pathways coupled to cCRHR1 can mediate CRH action. Collectively, our present study offers the first substantial evidence that hypothalamic CRH can stimulate pituitary CART1 expression via activation of CRHR1 in a vertebrate species.

  9. Simultaneous quantification of amphetamines, caffeine and ketamine in urine by hollow fiber liquid phase microextraction combined with gas chromatography-flame ionization detector.

    Science.gov (United States)

    Xiong, Jun; Chen, Jie; He, Man; Hu, Bin

    2010-08-15

    A method of hollow fiber (HF) liquid phase microextraction (LPME) combined with gas chromatography (GC)-flame ionization detection (FID) was developed for the simultaneous quantification of trace amphetamine (AP), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), caffeine and ketamine (KT) in drug abuser urine samples. The factors affecting on the extraction of six target analytes by HF-LPME were investigated and optimized, and the subsequent analytical performance evaluation and real sample analysis were performed by the extraction of six target analytes in sample solution containing 30% NaCl (pH 12.5) for 20 min with extraction temperature of 30 degrees C and stirring rate of 1000 rpm. Under such optimal conditions, the limits of detection (LODs, S/N=3) for the six target analytes were ranged from 8 microg/L (AP, KT) to 82 microg/L (MDA), with the enrichment factors (EFs) of 5-227 folds, and the relative standard deviations (RSDs, n=7) were in the range of 6.9-14.1%. The correlation coefficients of the calibration for the six target analytes over the dynamic linear range were higher than 0.9958. The application feasibility of HF-LPME-GC-FID in illegal drug monitoring was demonstrated by analyzing drug abuser urine samples, and the recoveries of target drugs for the spiked sample ranging from 75.2% to 119.3% indicated an excellent anti-interference capability of the developed method. The proposed method is simple, effective, sensitive and low-cost, and provides a much more accurate and sensitive detection platform over the conventional analytical techniques (such as immunological assay) for drug abuse analysis.

  10. Experience of clinical treatment to amphetamine-stimulants reliers%苯丙胺类兴奋剂依赖者临床治疗体会

    Institute of Scientific and Technical Information of China (English)

    卢金山; 吴峰; 张咏

    2011-01-01

    目的 总结苯丙胺类兴奋剂(amphetamin-type stimulants,ATS)依赖者的临床表现及治疗.方法 对104例符合DSM-Ⅳ诊断标准的ATS依赖者进行临床观察、治疗,并作出讨论.结果 ATS依赖者主要临床表现为:①中枢神经系统的作用.如精神兴奋、情感迸发、激动、感知觉障碍、定向障碍、精神病样反应、帕金森氏病样症状等.②系统作用.发热、心率快、血压高、食欲差、消瘦等.③戒断综合征.忧郁、焦虑、疲惫、全身肌肉疲软无力、头痛、固定型强迫行为等.治疗时,应建立一个安全、温馨的环境,给予患者充分的安慰,精神病样反应的患者给予其酚噻嗪类药物.结论 ATS是一种对中枢神经系统、心血管系统、人体行为有多种伤害作用的欢乐性兴奋剂.目前治疗只限于对症处理和进行长期严格监控、心理认知和行为干预.

  11. HPLC法测定甲基苯丙胺与苯丙胺%Detecting Methamphetamine and Amphetamine with High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    傅强; 廖林川; 陈礼莉; 颜有仪; 杨林; 侯俊红; 陈渝

    2007-01-01

    目的 建立甲基苯丙胺(methamphetamine,MA)和苯丙胺(amphetamine,AMP)的反相高效液相色谱测定方法.方法 采用C18柱,以甲醇-磷酸盐缓冲液为流动相,流速1.0 mL/min,检测波长为215 nm,同时收集190~360 nm的紫外光谱图,并以此与保留时间作为定性依据.在定性的基础上,建立定量检测方法,并对方法进行评价研究.结果 所建方法能良好分离MA和AMP,结合判断依据能准确定性;MA在1.4~270 μg/mL浓度范围内线性关系良好,R2=1,日内标准偏差(RSD)与日间RSD均<2.4%,检出限为0.73 μg/mL,平均加样回收率为102.5%;AMP在0.9~580 μg/mL浓度范围内线性关系良好,R2=0.9999,日内RSD与日间RSD均<2.3%,检出限为0.52 μg/mL,平均加样回收率为101.7%.结论 此方法简便、快速、准确,适用于MA与AMP的检测.

  12. Projection patterns of lateral hypothalamic, cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe and/or the locus coeruleus in the rat.

    Science.gov (United States)

    Yoon, Ye S; Lee, Hyun S

    2013-02-04

    The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

  13. Effect of desipramine and citalopram treatment on forced swimming test-induced changes in cocaine- and amphetamine-regulated transcript (CART) immunoreactivity in mice.

    Science.gov (United States)

    Chung, Sung; Kim, Hee Jeong; Kim, Hyun Ju; Choi, Sun Hye; Kim, Jin Wook; Kim, Jeong Min; Shin, Kyung Ho

    2014-05-01

    Recent study demonstrates antidepressant-like effect of cocaine- and amphetamine-regulated transcript (CART) in the forced swimming test (FST), but less is known about whether antidepressant treatments alter levels of CART immunoreactivity (CART-IR) in the FST. To explore this possibility, we assessed the treatment effects of desipramine and citalopram, which inhibit the reuptake of norepinephrine and serotonin into the presynaptic terminals, respectively, on changes in levels of CART-IR before and after the test swim in mouse brain. Levels of CART-IR in the nucleus accumbens shell (AcbSh), dorsal bed nucleus of the stria terminalis (dBNST), and hypothalamic paraventricular nucleus (PVN) were significantly increased before the test swim by desipramine and citalopram treatments. This increase in CART-IR in the AcbSh, dBNST, and PVN before the test swim remained elevated by desipramine treatment after the test swim, but this increase in these brain areas returned to near control levels after test swim by citalopram treatment. Citalopram, but not desipramine, treatment increased levels of CART-IR in the central nucleus of the amygdala (CeA) and the locus ceruleus (LC) before the test swim, and this increase was returned to control levels after the test swim in the CeA, but not in the LC. These results suggest common and distinct regulation of CART by desipramine and citalopram treatments in the FST and raise the possibility that CART in the AcbSh, dBNST, and CeA may be involved in antidepressant-like effect in the FST.

  14. Cocaine- and amphetamine-regulated transcript peptide (CART) in the brain of zebra finch, Taeniopygia guttata: Organization, interaction with neuropeptide Y, and response to changes in energy status.

    Science.gov (United States)

    Singh, Omprakash; Kumar, Santosh; Singh, Uday; Kumar, Vinod; Lechan, Ronald M; Singru, Praful S

    2016-10-15

    Cocaine- and amphetamine-regulated transcript (CART) has emerged as a potent anorectic agent. CART is widely distributed in the brain of mammals, amphibians, and teleosts, but the relevant information in avian brain is not available. In birds, CART inhibits food intake, whereas neuropeptide Y (NPY), a well-known orexigenic peptide, stimulates it. How these neuropeptides interact in the brain to regulate energy balance is not known. We studied the distribution of CART-immunoreactivity in the brain of zebra finch, Taeniopygia guttata, its interaction with NPY, and their response to dynamic energy states. CART-immunoreactive fibers were found in the subpallium, hypothalamus, midbrain, and brainstem. Conspicuous CART-immunoreactive cells were observed in the bed nucleus of the stria terminalis, hypothalamic paraventricular, supraoptic, dorsomedial, infundibular (IN), lateral hypothalamic, Edinger-Westphal, and parabrachial nuclei. Hypothalamic sections of fed, fasted, and refed animals were immunostained with cFos, NPY, and CART antisera. Fasting dramatically increased cFos- and NPY-immunoreactivity in the IN, followed by rapid reduction by 2 hours and restoration to normal fed levels 6-10 hours after refeeding. CART-immunoreactive fibers in IN showed a significant reduction during fasting and upregulation with refeeding. Within the IN, double immunofluorescence revealed that 94 ± 2.1% of NPY-immunoreactive neurons were contacted by CART-immunoreactive fibers and 96 ± 2.8% NPY-immunoreactive neurons expressed cFos during fasting. Compared to controls, superfused hypothalamic slices of fasted birds treated with CART-peptide showed a significant reduction (P CART in the brain of T. guttata may perform several functions, and has a particularly important role in the hypothalamic regulation of energy homeostasis. J. Comp. Neurol. 524:3014-3041, 2016. © 2016 Wiley Periodicals, Inc.

  15. Regulation of granulosa cell cocaine and amphetamine regulated transcript (CART) binding and effect of CART signaling inhibitor on granulosa cell estradiol production during dominant follicle selection in cattle.

    Science.gov (United States)

    Folger, Joseph K; Jimenez-Krassel, Fermin; Ireland, James J; Lv, Lihua; Smith, George W

    2013-12-01

    We previously established a potential role for cocaine and amphetamine regulated transcript (CARTPT) in dominant follicle selection in cattle. CARTPT expression is elevated in subordinate versus dominant follicles, and treatment with the mature form of the CARTPT peptide (CART) decreases follicle-stimulating hormone (FSH)-stimulated granulosa cell estradiol production in vitro and follicular fluid estradiol and granulosa cell CYP19A1 mRNA in vivo. However, mechanisms that regulate granulosa cell CART responsiveness are not understood. In this study, we investigated hormonal regulation of granulosa cell CART-binding sites in vitro and temporal regulation of granulosa cell CART-binding sites in bovine follicles collected at specific stages of a follicular wave. We also determined the effect of inhibition of CART receptor signaling in vivo on estradiol production in future subordinate follicles. Granulosa cell CART binding in vitro was increased by FSH, and this induction was blocked by estrogen receptor antagonist treatment. In follicles collected in vivo at specific stages of a follicular wave, granulosa cell CART binding in the F2 (second largest), future subordinate follicle increased during dominant follicle selection. Injection into the F2 follicle (at onset of diameter deviation) of an inhibitor of the o/i subclass of G proteins (previously shown to block CART actions in vitro) resulted in increased follicular fluid estradiol concentrations in vivo. Collectively, results demonstrate hormonal regulation of granulosa cell CART binding in vitro and temporal regulation of CART binding in subordinate follicles during dominant follicle selection. Results also suggest that CART signaling may help suppress estradiol-producing capacity of the F2 (subordinate) follicle during this time period.

  16. CART (cocaine- and amphetamine-regulated transcript) peptide specific binding sites in PC12 cells have characteristics of CART peptide receptors.

    Science.gov (United States)

    Nagelová, Veronika; Pirník, Zdeno; Železná, Blanka; Maletínská, Lenka

    2014-02-14

    CART (cocaine- and amphetamine-regulated transcript) peptide is a neuropeptide with a powerful central anorexigenic effect. Specific CART peptide binding sites, most likely CART peptide receptors, have been found in PC12 cells. This study further characterizes the CART peptide binding sites in PC12 cells. After differentiation to a neuronal phenotype with nerve growth factor, the number of CART peptide binding sites in PC12 cells tripled. Following dexamethasone treatment, which transforms PC12 cells into chromaffin-like cells, the number of CART peptide binding sites substantially decreased. CART peptide did not affect the differentiation or acetylcholinesterase activity of PC12 cells, indicating that CART peptide does not participate in differentiation or neuronal activity. CART peptide increased the phosphorylation of SAPK/JNK (stress-activated protein kinase/c-Jun-amino-terminal kinase) and subsequent c-Jun protein expression. These effects were reversed by SP600125, a specific JNK-kinase inhibitor. CART peptide did not significantly affect ERK (extracellular signal-regulated kinase), CREB (cAMP responsive element binding protein), or p38 phosphorylation and c-Fos protein expression. Central administration of CART peptide into mice also resulted in increased c-Jun positive cells in dorsomedial hypothalamic nucleus and nucleus of the solitary tract, areas involved in food intake regulation. Activation of c-Jun by CART peptide might indicate a possible role of CART peptide in managing stress conditions rather than a role in cell proliferation or differentiation as well as the more complex and/or specific regulation ways by transcription factors in some nuclei involved in food intake regulation. The characteristics of stress that CART peptide potentially mediates should be further studied.

  17. Microinjection of CART (cocaine- and amphetamine-regulated transcript) peptide into the nucleus accumbens inhibits the cocaine-induced upregulation of dopamine receptors and locomotor sensitization.

    Science.gov (United States)

    Peng, Qinghua; Sun, Xi; Liu, Ziyong; Yang, Jianghua; Oh, Ki-Wan; Hu, Zhenzhen

    2014-09-01

    Repeated exposure to addictive drugs enhances dopamine receptor (DR) signaling and the ultimate phosphorylation of the cyclic adenosine 5'-monophosphate (cAMP)-response element-binding protein (CREB)-regulated cocaine- and amphetamine-regulated transcript (CART) expression in the nucleus accumbens (NAcc). These effects are known to contribute to the expression of behavioral sensitization. CART peptides are neuropeptides that modulate drug reward and reinforcement. The present experiments investigated the effects of CART 55-102 microinjection into the NAcc on (1) the phosphorylation of CREB, (2) cAMP/protein kinase A (PKA) signaling and (3) extracellular signal-regulated kinase (ERK) phosphorylated kinase signaling. Here, we show that repeated microinjections into the NAcc of CART 55-102 peptides (1.0 or 2.5μg, 0.5μl/side) attenuates cocaine-induced enhancements of D1R, D2R and D3R phosphorylation in this sites. Furthermore, the microinjection of CART 55-102 followed by repeated injections of cocaine (15mg/kg) dose-dependently blocked the enhancement of cAMP levels, PKA activity and pERK and pCREB levels on the fifth day of cocaine administration. The cocaine-induced locomotor activity and behavioral sensitization in rats were also inhibited by the 5-day-microinjection of CART peptides. These results suggest that the phosphorylation of CREB by cocaine in the NAcc was blocked by the CART 55-102 peptide via the inhibition of D1R and D2R stimulation, D3R phosphorylation, cAMP/PKA signaling and ERK phosphorylated kinase signaling. These effects may have played a compensatory inhibitory role in the behavioral sensitization of rats that received microinjections of CART 55-102.

  18. The role of the polymorphic efflux transporter P-glycoprotein on the brain accumulation of d-methylphenidate and d-amphetamine.

    Science.gov (United States)

    Zhu, Hao-Jie; Wang, Jun-Sheng; DeVane, C Lindsay; Williard, Robin L; Donovan, Jennifer L; Middaugh, Lawrence D; Gibson, Brian B; Patrick, Kennerly S; Markowitz, John S

    2006-07-01

    The psychostimulant medications methylphenidate (MPH) and amphetamine (AMP), available in various ratios or enantiopure formulations of their respective active dextrorotary isomers, constitute the majority of agents used in the treatment of attention-deficit/hyperactivity disorder (ADHD). Substantial interindividual variability occurs in their pharmacokinetics and tolerability. Little is known regarding the potential role of drug transporters such as P-glycoprotein (P-gp) in psychostimulant pharmacokinetics and response. Therefore, experiments were carried out in P-gp knockout (KO) mice versus wild-type (WT) mice after intraperitoneal dosing (2.5 mg/kg) of d-MPH or (3.0 mg/kg) of d-AMP. After the administration of each psychostimulant, locomotor activity was assessed at 30-min intervals for 2 h. Total brain-to-plasma drug concentration ratios were determined at 10-, 30-, and 80-min postdosing time-points. The results showed no statistically supported genotypic difference in d-AMP-induced locomotor activity stimulation or in brain-to-plasma ratio of d-AMP. As for d-MPH, the P-gp KO mice had 33% higher brain concentrations (p gp compared with that for WT mice. These data indicate that P-gp has no apparent effect on the pharmacokinetics and pharmacodynamics of d-AMP. In addition, d-MPH is a relatively weak P-gp substrate, and its entry into the brain may be limited by P-gp. Furthermore, the mechanism by which d-MPH-induced locomotor activity was attenuated in P-gp KO mice remains to be elucidated.

  19. Effect of amphetamine on extracellular concentrations of amino acids in striatum in neurotensin subtype 1 and 2 receptor null mice: a possible interaction between neurotensin receptors and amino acid systems for study of schizophrenia

    OpenAIRE

    Li, Zhimin; Liang, Yanqi; Boules, Mona; Gordillo, Andres; Richelson, Elliott

    2010-01-01

    Neurotensin (NT) is a tridecapeptide that acts as a neuromodulator in the central nervous system mainly through two NT receptors: NTS1 and NTS2. The present study was done to determine the roles of NTS1 and NTS2 on amino acid release in striatum with the use of NTS1 or NTS2 knock-out (-/-) mice given d-amphetamine. Both NTS1-/- and NTS2-/- mice had lower extracellular concentrations of D-serine in striatum than did wild type (WT) mice. NTS2-/- but not NTS1-/- mice also had significantly lower...

  20. 苯丙胺类滥用致锥体外系综合征七例临床分析%Clinical analysis on 7 cases of extrapyramidal syndrome caused by abuse of amphetamine-type

    Institute of Scientific and Technical Information of China (English)

    卢金山; 吴峰; 张咏

    2011-01-01

    @@ 本文回顾性总结了拟交感性苯丙胺类兴奋剂(amphetamine type stmulants,ATS)依赖住院治疗病人104例,结果有7例出现帕金森氏(Parkinson)病样症状,现将其临床表现、治疗经过、ATS滥用致帕金森氏病样症状的发病机制进行总结分析,报告如下.

  1. 可卡因-苯丙胺调节转录肽在脑缺血中的神经保护机制%Neuroprotective mechanisms of cocaine-and amphetamine-regulated transcript peptides in brain ischemia

    Institute of Scientific and Technical Information of China (English)

    王路娜; 沙杜鹃; 张均

    2013-01-01

    可卡因-苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript peptides,CART)是一种存在于人和动物的内源性神经肽,参与调节体内多种生理和病理学过程.多项研究提示,CART在中枢神经系统中广泛分布,具有一定的中枢神经保护作用.文章对CART在脑缺血中的神经保护机制进行了综述.%Cocaine-and amphetamine-regulated transcript(CART) peptides are endogenous neurotransmitters with important roles in a number of physiological and pathological processes in vivo.Many studies suggested that CART is widely distributed in the central nervous system,and it has some central protective effects.This article reviews the recent progress in research on the protective effect of CART on cerebral ischemia and its mechanisms.

  2. Research progress about cocaine and amphetamine regulated transcript in diabetes%可卡因-苯丙胺转录调节肽与糖尿病关系研究进展

    Institute of Scientific and Technical Information of China (English)

    隆敏; 周世文

    2012-01-01

    可卡因-苯丙胺转录调节肽(cocaine and amphetamine regulated transcript,CART)是一种丰富表达下丘脑及胰腺组织的神经肽.该文就CART基因表达与糖尿病易感性、CART对进食和胰岛素分泌的调节及其自身表达调控、CART受体及可能的受体后信号通路进行阐述,并提出CART与糖尿病关系,研究亟待解决的问题.%Cocaine and amphetamine regulated transcript (CART) is a recently described neuropeptide widely expressed in the hypothalamus and pancreas. This review describes the re -lationship between CART gene expression and the susceptibility to diabetes, the evidences of CART in food intake and insulinsecretion, and CART expression modulation. Finally, CART receptors and potential post receptor signaling pathways are also described, problems to be solved are put forward as well.

  3. Simultaneous qualitative and quantitative method using liquid chromatography selected reaction monitoring-triggered quantitation-enhanced data-dependent tandem mass spectrometry for the identification and classification of amphetamine-type stimulant abusers in human urine.

    Science.gov (United States)

    Lee, Sang Kyu; Kim, So-Hee; Kim, Ho Jun; Yoo, Hye Hyun; Kwon, Oh Seung; In, Moon Kyo; Jin, Changbae; Kim, Dong Hyun; Lee, Jaeick

    2010-11-15

    Amphetamine (AP) and amphetamine-type stimulants, methamphetamine (MA) and N,N-dimethylamphetamine (DMA), are known as central nervous system stimulants, and their abuse throughout the world has recently increased. Since it is difficult to physically distinguish among AP, MA and DMA, analysts may not be aware of what abusers have administered. In this study, following the detection of specific metabolites of AP, MA and DMA as biomarkers in abuser urines, a rapid and sensitive method was developed for the identification and classification of AP-type stimulants abusers. After the simple filtration of the urine samples, the samples were directly analyzed using a liquid chromatography/tandem mass spectrometry system with selected reaction monitoring (SRM)-triggered quantitation-enhanced data-dependent MS/MS (QED-MS/MS) for the simultaneous qualitative and quantitative analysis of p-hydroxy AP, p-hydroxy MA, p-hydroxy DMA, AP, MA, DMA and DMA N-oxide. The determination of p-hydroxy AP, p-hydroxy MA, AP, MA, DMA and DMA N-oxide was accurate and reproducible, with the limits of quantitation of 5 ng/mL in urine. When applied to the urine samples of suspected AP-type stimulants abusers, the abused drugs were precisely identified between MA and DMA abusers.

  4. Amphetamine and environmentally induced hyperthermia differentially alter the expression of genes regulating vascular tone and angiogenesis in the meninges and associated vasculature.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Patterson, Tucker A; Bowyer, John F

    2009-10-01

    An amphetamine (AMPH) regimen that does not produce a prominent blood-brain barrier breakdown was shown to significantly alter the expression of genes regulating vascular tone, immune function, and angiogenesis in vasculature associated with arachnoid and pia membranes of the forebrain. Adult-male Sprague-Dawley rats were given either saline injections during environmentally-induced hyperthermia (EIH) or four doses of AMPH with 2 h between each dose (5, 7.5, 10, and 10 mg/kg d-AMPH, s.c.) that produced hyperthermia. Rats were sacrificed either 3 h or 1 day after dosing, and total RNA and protein was isolated from the meninges, arachnoid and pia membranes, and associated vasculature (MAV) that surround the forebrain. Vip, eNos, Drd1a, and Edn1 (genes regulating vascular tone) were increased by either EIH or AMPH to varying degrees in MAV, indicating that EIH and AMPH produce differential responses to enhance vasodilatation. AMPH, and EIH to a lesser extent, elicited a significant inflammatory response at 3 h as indicated by an increased MAV expression of cytokines Il1b, Il6, Ccl-2, Cxcl1, and Cxcl2. Also, genes related to heat shock/stress and disruption of vascular homeostasis such as Icam1 and Hsp72 were also observed. The increased expression of Ctgf and Timp1 and the decreased expression of Akt1, Anpep, and Mmp2 and Tek (genes involved in stimulating angiogenesis) from AMPH exposure suggest that angiogenesis was arrested or disrupted in MAV to a greater extent by AMPH compared to EIH. Alterations in vascular-related gene expression in the parietal cortex and striatum after AMPH were less in magnitude than in MAV, indicating less of a disruption of vascular homeostasis in these two regions. Changes in the levels of insulin-like growth factor binding proteins Igfbp1, 2, and 5 in MAV, compared to those in striatum and parietal cortex, imply an interaction between these regions to regulate the levels of insulin-like growth factor after AMPH damage. Thus, the

  5. MCG101-induced cancer anorexia-cachexia features altered expression of hypothalamic Nucb2 and Cartpt and increased plasma levels of cocaine- and amphetamine-regulated transcript peptides.

    Science.gov (United States)

    Burgos, Jonathan R; Iresjö, Britt-Marie; Smedh, Ulrika

    2016-04-01

    The aim of the present study was to explore central and peripheral host responses to an anorexia-cachexia producing tumor. We focused on neuroendocrine anorexigenic signals in the hypothalamus, brainstem, pituitary and from the tumor per se. Expression of mRNA for corticotropin-releasing hormone (CRH), cocaine- and amphetamine-regulated transcript (CART), nesfatin-1, thyrotropin (TSH) and the TSH receptor were explored. In addition, we examined changes in plasma TSH, CART peptides (CARTp) and serum amyloid P component (SAP). C57BL/6 mice were implanted with MCG101 tumors or sham-treated. A sham-implanted, pair‑fed (PF) group was included to delineate between primary tumor and secondary effects from reduced feeding. Food intake and body weight were measured daily. mRNA levels from microdissected mouse brain samples were assayed using qPCR, and plasma levels were determined using ELISA. MCG101 tumors expectedly induced anorexia and loss of body weight. Tumor-bearing (TB) mice exhibited an increase in nesfatin-1 mRNA as well as a decrease in CART mRNA in the paraventricular area (PVN). The CART mRNA response was secondary to reduced caloric intake whereas nesfatin-1 mRNA appeared to be tumor-specifically induced. In the pituitary, CART and TSH mRNA were upregulated in the TB and PF animals compared to the freely fed controls. Plasma levels for CARTp were significantly elevated in TB but not PF mice whereas levels of TSH were unaffected. The plasma CARTp response was correlated to the degree of inflammation represented by SAP. The increase in nesfatin-1 mRNA in the PVN highlights nesfatin-1 as a plausible candidate for causing tumor-induced anorexia. CART mRNA expression in the PVN is likely an adaptation to reduced caloric intake secondary to a cancer anorexia-cachexia syndrome (CACS)‑inducing tumor. The MCG101 tumor did not express CART mRNA, thus the elevation of plasma CARTp is host derived and likely driven by inflammation.

  6. Study on Reaction Mechanism and Their Structure -Activity Relationship between Three Amphetamines and Lysozyme%3种苯丙胺类药物与溶菌酶的作用机制及构效关系研究

    Institute of Scientific and Technical Information of China (English)

    张爱平; 黄茜; 郝娟; 文雯; 高晓亚

    2011-01-01

    在模拟人体生理条件下,采用荧光光谱法研究了3种不同结构的苯丙胺类药物(麻黄碱、伪麻黄碱和甲基麻黄碱)与溶菌酶之间的相互作用,计算了其结合常数、结合位点数和热力学参数,并探讨了3种药物对溶菌酶构象的影响.研究发现,三者可对溶菌酶内源性荧光产生强烈的猝灭作用,其猝灭过程均为静态猝灭.麻黄碱、伪麻黄碱和甲基麻黄碱与溶菌酶均形成1 :1复合物,在308 K温度下的结合常数K分别为5.11×103、4.04×103、2.80×103 L·mol-1,结合距离r分别为0.241、0.350、0.422 nm,与溶菌酶结合的焓变分别为-123、-126、-52.1 kJ·mol-1,熵变分别为-329、-339、-103 J·mol-1·K-1.研究结果表明,苯丙胺类药物的构型和取代基对其与溶菌酶的相互作用有重要影响,3种苯丙胺类药物与溶菌酶的作用力顺序为麻黄碱>伪麻黄碱>甲基麻黄碱,体系的主要作用力为氢键和范德华力.溶菌酶与3种药物的同步荧光光谱也表明,溶菌酶的构象在作用前后基本不变.%The interactions of lysozyme with ephedrine, pseudoephedrine and methylephedrine, as well as their structure -activity relationship were investigated by fluorescence spectrometry under simulative physiological conditions. The binding constant, the number of binding sites and the thermodynamic parameters were calculated and the effects of ephedrine, pseudoephedrine and methylephedrine on the conformation of lysozyme were studied. The results showed that the endogenous fluorescence of lysozyme was significantly quenched by ephedrine, pseudoephedrine and methylephedrine.The mechanism of fluorescence quenching was static quenching. The 1 : 1 complex was formed between each amphetamine and lysozyme. The binding constants K of ephedrine, pseudoephedrine and methylephedrine were 5.11×103, 4. 04 × 103 , 2. 80 × 103 L · mol-1, respectively. According to the theory of Fǒster dipole -dipole non-radiation energy

  7. 安非他明类毒品的手性对映体气相色谱-质谱分析%Enantiomer Separation and Determination of Amphetamines with Chiral Derivatization by Gas Chromatography-Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    孟品佳

    2001-01-01

    采用手性衍生化试剂:(S)(-)N-三氟乙酰-1-脯胺酰氯(TPC)和(R)(+)-α-甲氯基-α-三氟甲基苯乙酸(MTPA)与安非他明类对映体反应生成非对映体衍生化产物,通过常规的GC/MS方法将其分离。本文较系统地考察了这两种手性试剂衍生化反应中溶剂、手性试剂用量、加热温度、反应时间等因素对安非他明类对映体衍生化结果的影响。实现了Am、MAm、MDA、MDMA、MDEA、MBDB等几种毒品对映体间的良好分离。%Most drugs of amphetamines contain chiral centers, which form different optical isomers, or enantiomers. Because different enantiomers have different pharmcological effect and have different machnism of metabolism. Besides, the ratio of the two eanatiomers could reflect the route and method used in the synthesis of the drugs. So the separation and determination of these eanantiomers for seizured samples or for biological samples became very important in the sence of forensic science.The paper used two chiral reagents: N-trifluroacetylprolyl chloride (TPC) and ( R )-( + )-α-methoxy-α-(trifluormethyl)phenylacetic acid (MTPA) to reach the purpose. They reacted with amphetamine enantiomers to form diasteromeric pairs, which possess some diffeences in physical and chemical natures and could be separated by GC/MS. The paper examined in detail some fectors such as the solvents, chiral reagent amounts, reaction time,temperature,etc. on the effect of chiral derivatization. Some enantiomers of amphetamine (Am),N-methylamphetamine(MAm),3,4-methylenedioxyamphetamin (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3, 4-methylenedioxy-N-ethylamphetamine ( MDEA ) and N-methyl-1-( 3, 4-methylenedioxy )-2-butanamine (MBDB) were well separated each other.

  8. Research about attention network of patients with amphetamine-induced psychiatric disorders%冰毒所致精神障碍患者的注意网络功能研究

    Institute of Scientific and Technical Information of China (English)

    王会; 乔健; 赵秀芝; 苏中华

    2010-01-01

    Objective To investigate the characteristics of the cognitive impairment about attentional network among amphetamine-induced psychiatric disorders. Methods Amphetamine-induced psychiatric disorders ( n = 100) and normal controls ( n = 100) were assessed with Attentional Network Test(ANT) in the first week and the fourth week. Results Compared with the control group, the first ANT's response time was significantly increased, and the correct rate, orienting and executive control network were significantly reduced in Amphetamineinduced psychiatric disorders( eg:response time ( 867. 37 ± 272.24 ) ms vs ( 668.56 ± 136. 20 ) ms, correct rate (0.88 ±0.06 ) ms vs (0.88 ±0.06) ms ,orienting( - 217.86 ± 198.00 ) ms vs ( -59.67 ± 85.07 ) ms and executive control network ( 184.74 ± 66.61 ) ms vs ( 74.71 ± 50.77 ) ms, P < 0.01 ), but the alerting network was higher ( ( 151.17 ± 198.27 ) ms vs (50.60 ± 67.47 ) ms). In the second ANT results, there was no significant difference between two groups. Compared with the first ANT results of amphetamine-induced psychiatric disorders, the second ANT had shorten response time ,that the correct rate, orienting and executive control network were significantly increased(P < 0.01 ). Conclusion These results suggest that amphetamine-induced psychiatric disorders have impairment in cognitive function, but these impairment can be recovered within one month.%目的 探讨冰毒所致精神障碍患者注意网络认知功能缺损的特征.方法 对100例冰毒所致精神障碍者入院第1周和入院第4周进行注意网络功能测试(ANT).结果 (1)与对照组相比,冰毒所致精神障碍组第1次ANT的平均反应时明显延长,正确率、定向作用和执行控制功能明显下降[如:平均反应时(867.37±272.24)ms,(668.56±136.20)ms;正确率(0.88±0.06)ms,(0.88±0.06)ms;定向作用(-217.86±198.0)ms,(-59.67±85.07)ms;执行控制功能(184.74±66.61)ms,(74.71±50.77)ms,P<0.01],而警觉

  9. Distribution and chemical coding patterns of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) neurons in the enteric nervous system of the porcine stomach cardia.

    Science.gov (United States)

    Rękawek, W; Sobiech, P; Gonkowski, S; Żarczyńska, K; Snarska, A; Waśniewski, T; Wojtkiewicz, J

    2015-01-01

    The aim of this study was to determine the presence of cocaine- and amphetamine-regulated transcript-like immunoreactive (CART-LI) neurons and co-localisation of CART with vesicular acetylcholine transporter (VAChT), neuronal nitric oxide synthase (n-NOS), vasoactive intestinal polypeptide (VIP), substance P (SP) and leu-enkephalin (LENK) in the enteric nervous system of the porcine gastric cardia by using a double-labelling immunofluorescence technique. CART-LI neurons were observed in the myenteric plexus (18.2±2.6%). A dense network of CART-LI nerve fibers was mainly observed in the muscular layer. CART showed co-localization mainly with VAChT, n-NOS, VIP and to a lesser degree with LENK and SP. Distribution of CART and its co-localization with other neurotransmitters suggest that this peptide plays an important role in gastric motility in the pig.

  10. Protective effect of cocaine-and amphetamine-regulated transcript peptide in ischemic brain injury%可卡因-苯丙胺调节转录肽在缺血性脑损伤中的保护作用

    Institute of Scientific and Technical Information of China (English)

    金佳丽; 徐运

    2010-01-01

    可卡因-苯丙胺调节转录肽(cocaine-and amphetamine-regulated transcript,CART)是一种内源性神经肽,广泛分布于脑、胃肠道和胰腺等器官组织,具有多种重要的生理功能,包括进食与肥胖、应激、精神焦虑行为、药物成瘾和内分泌调节等.前期研究提示,CART在中枢神经系统广泛分布,并且参与调节多种生理学过程,具有一定的中枢保护作用,是一种很有潜力的神经保护剂.文章就CART对卒中以及神经变性疾病的神经保护作用及其机制,以及其在中枢神经系统疾病治疗作用等方面的研究进展进行了综述.%Cocaine-and amphetamine-regulated transcript (CART), an endogenous neuropeptide, is widely distributed in human organs and tissues, such as brain, gastrointestinal tract and pancreas. It has a variety of important physiological functions, including eating and obesity, stress, mental anxiety, drug addition, and endocrine regulation. Previous studies have suggested that CART is widely distributed in the central nervous system, and it involves in the regulation of a variety of physiological processes and has some central protective effects. It is a potential neuroprotective agent. This article reviews the recent progress in research on the neuroprotective effect of CART on stroke and neurodegenerative disease and its mechanisms, as well as its therapeutic effect in central nervous system diseases.

  11. The effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus.

    Science.gov (United States)

    Winter, J C

    1975-10-14

    The effects of mescaline (3,4,5-trimethoxyphenylethylamine), a hallucinogen, can function as a discriminative stimulus in appropriately trained rats. As a test of the hypothesis that those pharmacologic properties which distinguish hallucinogens and non-hallucinogens in man are reflected in distinctive stimuli in rats, the present experiments examined the effects of 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-ethylamphetamine (DOET), d-amphetamine, and cocaine in rats trained with mescaline as a discriminative stimulus. Administration of a range of doses of DOM and DOET to subjects in which saline functioned as SD and mescaline as Sdelta revealed that a dose of 0.3 mg of either DOM or DOET was equivalent to the training dose of mescaline. When tested in rats in which mescaline served as SD, DOM and DOET were likewise found to mimic mescaline. In contrast, doses of d-amphetamine and cocaine (1 and 30 mg/kg, respectively) which were equivalent to the training dose of mescaline as Sdelta, did not result in responding appropriate for the mescaline condition when mescaline was trained as SD. When DOET (0.3 mg/kg) was substituted for saline as Sdelta, no evidence of discriminated responding was obtained in the course of 50 sessions. The present data, in conjunction with previous observations, suggest that those effects of mescaline in the rat which function as a discriminative stimulus are better correlated with pre-hallucinogenic LSD-like activity in man then with hallucinogenic activity per se. Thus, these effects in rats represent a necessary but not a sufficient condition for prediction of hallucinogenic activity in man.

  12. Severe poisoning after self-reported use of 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine, a novel substituted amphetamine: a case series.

    Science.gov (United States)

    Hieger, M A; Rose, S R; Cumpston, K L; Stromberg, P E; Miller, S; Wills, B K

    2015-12-01

    Significant toxicity from amphetamine and cathinone derivatives is being increasingly reported. We describe a series of self-reported exposures to 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25-I-NBOME or 25-I), a novel amphetamine derivative. Ten patients with an average age of 17 years presented to local emergency departments (EDs) in our community after ingestion and/or insufflation of a drug referred to as "25-I." Of 10 patients, 6 reported taking 25-I alone; other substances included ethanol; 2,5-dimethoxy-4-ethylphenethylamine; marijuana; and ketamine. Most common effects included tachycardia (90%), hypertension (70%), agitation (60%), and hallucinations (50%). The average heart rate was 123 beats per minute. Two patients were found in status epilepticus, and another was found unresponsive. One patient who had a seizure had multiple, discrete intraparenchymal hemorrhages and acute kidney injury. Six patients were admitted to the intensive care unit, two were treated in the ED and released, and 1 each was admitted to psychiatry or managed in a clinical decision unit and subsequently discharged. Three patients required emergent intubation, and all admitted patients (7/10) were given intravenous benzodiazepines for sedation. Urine and blood specimens were obtained from 1 patient, which showed analytic confirmation of 25-I. In addition to sympathomimetic effects, methoxy and other substituent groups impart serotonergic effects, resulting in hallucinogenic properties. 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine appears to be extremely potent with a reported "dose" of 500 μg resulting in increased potential for inadvertent overdose. This case series describes significant morbidity in a local cluster of young patients after self-reported use of 25-I, a newly identified drug of abuse.

  13. Study of the metabolism of the new designer drugs of β-ketone analogs of amphetamines%苯丙胺类兴奋剂β酮策划药代谢途径的研究进展

    Institute of Scientific and Technical Information of China (English)

    孟品佳

    2012-01-01

    The new designer drugs of (J-ketone analogs of amphetamines were emerged recently in drug markets of many countries. They have been made illegal in many countries because of their potential for addiction and the associated health risks. The paper presents the relevant research results of derivatives of amphetamine, named mephedrone, methylone (bk-MDMA), butylone (bk-MBDB), and ethylone (bk-MDEA), with gas chromatography-mass spectrometry(GC/MS) and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI/MS) , proposed their main metabolism routs. The information on their metabolism will greatly help control the use of the drugs and investigate the cause of acute intoxication in forensic and clinical toxicology.%近年来,苯丙胺类兴奋剂的β酮(bK)策划药相继在许多国家的毒品市场中出现,由于该类物质潜在的依赖性和已经导致的死亡事件,许多国家已经将其列为管制的物质.本文介绍了通过GC/MS和LC/MS方法对苯丙胺类兴奋剂的衍生物4-甲基甲卡西酮、bk-MDMA、bk-MBDB和bk-MDEA检测的相关研究结果,以说明其主要代谢途径.以期为临床医学、法庭毒理学以及禁毒机构监控该类物质提供参考.

  14. The Clinical Features of Mental Disorder Due to Amphetamine Type Stimulants%苯丙胺类兴奋剂所致精神障碍临床特征分析

    Institute of Scientific and Technical Information of China (English)

    杨拓; 刘丽; 马力; 张陆贤

    2015-01-01

    目的:探讨苯丙胺类兴奋剂所致精神障碍临床特点。方法对2010~2013年在南宁市社会福利医院药物依赖科住院治疗的132例ATS所致精神病性障碍临床资料进行回顾性分析。结果滥用ATS类兴奋剂男女性别差异不大,文化素质偏低职业以无业和个体为主。76例(57.6%)曾经使用或合并使用其他物质。常见的精神病性症状为幻听112例(84.8%)、被害妄想124例(93.9%)、嫉妒妄想96例(72.7%)、易激惹120例(90.9%)、兴奋状态124例(93.9%)、冲动行为104例(78.8%)。经治疗症状在一个月内显效率97.4%。结论长期滥用苯丙胺类兴奋剂可致严重的精神病性障碍。治疗以对症治疗为主,并辅以心理治疗,总体疗效尚佳。%Objective To discuss the clinical features of mental disorder due to amphetamine type stimulants. Methods 132 Clinical data of psychotic disorder caused by ATS were retrospectively was analyzed from 2010 to 2013 in Nanning City Social Welfare Institute in Drug Dependence department. Results The abuse of amphetamine type stimulants had no sex difference. The low cultural quality was to unemployed and individual. 19 cases(57.6%)had used or combined with other substances. Psychotic symptoms common to auditory hal ucinations in 28 cases(84.8%),31(93.9%)cases of paranoia, delusions of jealousy in 24 cases(72.7%),irritable in 30 cases(90.9%),the excited state in 31 cases(93.9%),impulsive behavior in 26 cases(78.8%). After treatment,the significantly efficiency of symptoms was 97.4% within a month. Conclusion The mental disorders can be severe if abuse amphetamine type stimulants. Symptomatic treatment,supplemented by psychological treatment,the overal effect is comparatively good.

  15. MiRNAs在苯丙胺类兴奋剂成瘾中作用的研究进展%Research progress on the role of miRNAs in amphetamine-type stimulants addiction

    Institute of Scientific and Technical Information of China (English)

    江明金; 李婵; 林莹波; 朱道琦; 莫志贤

    2015-01-01

    Amphetamine-type stimulants ( ATS ) , a group of new-type synthetic drugs mainly in psychological dependence, are abused more and more severely in recent years. MicroRNAs ( MiRNAs ) are an important class of endogenous non-coding small RNAs that mediate posttranscriptional negatively regulation of gene expression by targeting specific mRNA sequences to in-hibit the translation of mRNAs or degrade the expression of mR-NAs. ATS can induce the changes in the expression of miRNAs in addiction-related brain regions which directly involve in the regulation of ATS-induced addictive behaviors. Therefore, to study the regulatory role of miRNAs in ATS-induced addiction has important implications for dependent mechanisms of new-type drugs and the discovery of the new targets of drug actions.%苯丙胺类兴奋剂( amphetamine-type stimulants,ATS)是一组以精神依赖为主的新型合成毒品,近年来流行,滥用趋势愈发严峻。 MicroRNAs( MiRNAs)作为一类非编码小分子RNAs,通过与靶基因mRNA的互补配对,在转录后水平上对基因的表达进行负调控,从而导致靶基因mRNA的降解或翻译抑制。 ATS能诱导miRNAs表达水平的变化,而成瘾相关脑区miRNAs表达的改变直接参与了对ATS成瘾行为的调节。因此,研究miRNAs在ATS成瘾中的调控作用,对进一步揭示新型毒品的成瘾机制及发现新的药物作用靶点具有重要意义。

  16. Identification of Amphetamine-type Stimulants Using Gas Chromatography Coupled with Fourier Transform Infrared Spectroscopy%苯丙胺类毒品及其衍生物的气相色谱-红外光谱分析

    Institute of Scientific and Technical Information of China (English)

    张润生; 王跨陡; 龚飞君; 叶海英; 张玉荣; 严松茂; 杜一平; 张维冰

    2012-01-01

    采用气相色谱一傅立叶变换红外光谱联用技术,建立了9种苯丙胺类毒品及其衍生物的分析鉴别方法.采用HP-1(30 m×0.32 mm,0.25 μm)毛细管柱,MCT红外检测器与氢火焰检测器同时检测,在程序升温条件下,以十七烷为内标物,研究已知对照品的色谱保留行为及其气态红外光谱图特征,建立相应的特征吸收峰数据库,作为鉴别分析的依据.色谱保留时间与红外特征吸收峰联合鉴别法极大地提高了鉴别的准确性.将发展的方法应用于可疑毒品物证中苯丙胺类及其衍生物毒品样品的鉴别,获得了理想的结果.本方法可用于涉毒案件毒品物证的检验,特别适用于混合毒品成分的检验.%Gas chromatography-infrared spectroscopy technique has been used for the quantitative analysis of amphetamine-type stimulants. Capillary column of HP-1 (30 m×0. 32 mm. 0. 25 μm) was coupled with MCT infrared spectroscopy and flame ionization detecters using temperature programming for identification of nine ampletamine-type stimulants. Chromatographic retention behaviors were studied using heptadecane as internal standard for separation and identification of the stimulants. On another hand, infrared spectra of the gaseous amphetamine-type stimulants were measured using chemical reference substances of the stimulants and the characteristic peaks from the collected spectra were supplied as an assistant identification. The cooperation of information from retention time and infrared spectrum should improve the reliability of the method. The analysis of real samples showed satisfactory results. The method could be applied to the stimulant identification, especially to that of complicated sample.

  17. 实时直接分析离子源-飞行时间质谱法快速筛查安非他明类物质%Rapid Screening of Amphetamines by Time-of-Flight Mass Spectrometry Coupled with Direct Analysis in Real Time Ion Source

    Institute of Scientific and Technical Information of China (English)

    连茹; 吴忠平; 吕小宝; 汪蓉; 倪春芳; 张玉荣

    2016-01-01

    A method for rapid screening of 8 amphetamines in drug samples was developed based on time of flight mass spectrometry (TOF-MS)coupled with direct analysis in real time (DART)ion source.Ion source temperature of 400 ℃,grid voltage of 200 V and the injection rate of 0.4 mm·s-1 were adopted in DART,and positive ion mode and orificel voltages of 30,60 V were adopted in TOF-MS for analysis of the 8 amphetamines.A screening database of accurate relative molecular mass of informative precursor ions and fragment ions was established for the rapid qualitative analysis of the 8 amphetamines in drug samples.The detection limits of the 8 amphetamines ranged from 0.05 to 0.1 mg·L-1 .The fragmentation regularity of the 8 amphetamines in DART ion source was analysized.%采用实时直接分析(DART)离子源结合飞行时间质谱法(TOF-MS),提出了一种快速筛查毒品检材中安非他明类物质的方法。DART 离子源温度400℃,栅极电压200 V,进样速率0.4 mm·s-1。飞行时间质谱中选择正离子模式,孔1电压为30 V 和60 V,分析8种安非他明类物质。通过得到的具有精确相对分子质量的准分子离子峰和两个以上的碎片离子峰建立筛查数据库,对检材中的安非他明类物质进行快速定性分析。8种安非他明类物质的检出限在0.05~0.1 mg·L-1之间。并分析了8种安非他明类物质在 DART 离子源下的裂解规律。

  18. The harm of the abuse of amphetamine-type stimulants and its related interventional measures%苯丙胺类物质滥用危害及相关干预措施

    Institute of Scientific and Technical Information of China (English)

    杜江; 赵敏

    2014-01-01

    苯丙胺类物质以损害认知功能为主,使用者主要表现为幻觉、妄想、记忆力下降等精神症状和认知功能障碍,并且在上述精神症状影响下可能出现一系列的冲动、伤人及自伤行为。本文就苯丙胺类物质在我国的滥用趋势、作用机制、相关危害、治疗和干预措施进行介绍,以提高公众对其认识,降低苯丙胺类物质滥用对患者自身和社会的危害。%Amphetamine-type stimulants(AST)can damage the cognitive function of drug addicts who present mental symptoms as cognitive disfunction, delusions and hallucinations, which results in a series of impulse, wounding and self-injury behavior. This article introduces the epidemiological trend, the mechanism, the related hazard, the treatment and interventional measures of AST in our country in order to improve the awareness of AST in the publics and reduce AST harm to drug addicts and society.

  19. 苯丙胺类物质滥用者高危行为性别差异的分析%THE CHARACTERISTIC OF HIGH-RISK BEHAVIOR AND THE GENDER DIFFERENCES IN AMPHETAMINE-TYPE STIMULANTS USERS

    Institute of Scientific and Technical Information of China (English)

    杜哲一; 李质彬; 陶凤英; 孙海明; 陈志康; 杜江; 赵敏

    2014-01-01

    目的:了解不同性别苯丙胺类物质(amphetamine-type stimulants,ATS))滥用者一般人口学特征、毒品使用情况和高危行为的差异.方法:采用横断面调查研究,对来自上海强制隔离戒毒所的377名ATS滥用者进行调查.结果:不同性别的ATS滥用者在毒品滥用史,高危行为方面存在显著差异.女性患者首次使用年龄较男性更早,使用ATS后发生即刻性行为、有多个性伴侣的比例均高于男性,且性伴侣在性行为中更少使用安全套.此外,女性患者更多出现自杀观念和自杀行为.而男性患者使用ATS后的性冲动显著高于女性.结论:不同性别的ATS滥用者在毒品使用及高危行为方面存在差异.工作人员应当对不同性别的使用者制定针对性的干预措施.

  20. Beta-keto amphetamines: studies on the metabolism of the designer drug mephedrone and toxicological detection of mephedrone, butylone, and methylone in urine using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Meyer, Markus R; Wilhelm, Jens; Peters, Frank T; Maurer, Hans H

    2010-06-01

    In recent years, a new class of designer drugs has appeared on the drugs of abuse market in many countries, namely, the so-called beta-keto (bk) designer drugs such as mephedrone (bk-4-methylmethamphetamine), butylone (bk-MBDB), and methylone (bk-MDMA). The aim of the present study was to identify the metabolites of mephedrone in rat and human urine using GC-MS techniques and to include mephedrone, butylone, and methylone within the authors' systematic toxicological analysis (STA) procedure. Six phase I metabolites of mephedrone were detected in rat urine and seven in human urine suggesting the following metabolic steps: N-demethylation to the primary amine, reduction of the keto moiety to the respective alcohol, and oxidation of the tolyl moiety to the corresponding alcohols and carboxylic acid. The STA procedure allowed the detection of mephedrone, butylone, methylone, and their metabolites in urine of rats treated with doses corresponding to those reported for abuse of amphetamines. Besides macro-based data evaluation, an automated evaluation using the automated mass spectral deconvolution and identification system was performed. Mephedrone and butylone could be detected also in human urine samples submitted for drug testing. Assuming similar kinetics in humans, the described STA procedure should be suitable for proof of an intake of the bk-designer drugs in human urine.

  1. Effect of l- tetrahydropalmatine on the conditional place preference produced by amphetamine%左旋四氢巴马汀对苯丙胺条件性位置偏爱效应的影响

    Institute of Scientific and Technical Information of China (English)

    周媛; 邢淑华

    2002-01-01

    目的观察左旋四氢巴马汀(l-tetrahydropalmatine,l-THP)对苯丙胺(Amphetamine,AA)的条件性位置偏爱(conditional place preference,CPP)效应的影响.方法采用倾向性训练程序训练大鼠,建立位置偏爱模型和建立氢化可的松诱发位置偏爱效应重现模型,并观察l-THP对其影响.结果l-THP 10 mg·kg-1可阻断AA 2.0mg·kg-1的位置偏爱效应,并且可阻止氢化可的松10 mg·kg-1诱发的位置偏爱效应的重现.结论AA可使大鼠出现条件性位置偏爱效应,并在一定剂量范围内(0.5~4.0 mg·kg-1)呈量效关系(r=0.94);氢化可的松可使已消失的位置偏爱效应重现;以上2种效应均可被l-THP阻断.

  2. Influence of amphetamine-type stimulants on serum rapid plasma reagent titer in patients with syphilis%苯丙胺类兴奋剂对梅毒患者血RPR滴度的影响

    Institute of Scientific and Technical Information of China (English)

    李永喜; 张建明; 曲才杰; 毕健平; 李春霞

    2009-01-01

    目的 探讨苯丙胺类兴奋剂对梅毒患者血RPR滴度及阴转率的影响.方法 收集36例吸食苯丙胺类毒品的梅毒患者资料,取外周血检测RPR滴度、阴转率和免疫球蛋白水平,检测外周血单一核细胞产生IFN-γ、lL-4水平,并以44例梅毒患者和30例健康人作对照.结果 试验组RPR滴度明显低于对照组(P0.05),试验组IFN-γ水平低于对照组(P 0.05). The capability of PBMCs to product IFN-γ was highest in the stimulant-taking group, followed by the non-taking group and normal control group (all P < 0.05). No significant difference was observed in the capability of PBMCs to produce IL-4 between the stimulant-taking group and non-taking group, but a significant increment was noted in these patients compared with the normal human controls (all P < 0.01). Conclusion Amphetamine-type stimulants could reduce serum RPR titer and negative conversion rate of RPR in patients with syphilis, likely by impairing cellular immunity of patients.

  3. 苯丙胺类兴奋剂使用障碍者酒精滥用情况调查%SURVEY ON ALCOHOL USEPROBLEMS AMONG PATIENTS WITH AMPHETAMINE-TYPE STIMULUS USE DISORDERS

    Institute of Scientific and Technical Information of China (English)

    李煦; 汪文文; 李传威; 张乔阳; 庄文旭; 赵燕; 江海峰; 赵敏

    2015-01-01

    目的:了解我国苯丙胺类兴奋剂苯丙胺类兴奋剂(amphetamine-type stimulants,ATS)使用障碍者酒精滥用发生率及相关因素.方法:采用酒精依赖识别测验(The Alcohol Use Disorders Identification Test,AUDIT)对540例ATS使用障碍者进行酒精使用障碍筛查,并收集一般人口学资料、吸毒史、ATS使用情况和酒精使用情况.结果:30.7%的ATS使用障碍患者存在酒精使用障碍.Logistic回归分析发现与“嗨姝/哥”一起使用、通常在家里使用ATS与合并酒精滥用问题相关.结论:ATS使用障碍者合并酒精使用障碍者比例较高,应当关注ATS使用者中的酒精问题的防治工作,以降低多物质滥用危害.

  4. Immunohistochemical distribution of cocaine and amphetamine regulatory peptide-like immunoreactive (CART-LI) nerve fibers in the circular muscle layer and their relationship to other peptides in the human caecum.

    Science.gov (United States)

    Bulc, Michał; Gonkowski, Sławomir; Landowski, Piotr; Kamińska, Barbara; Całka, Jarosław

    2014-07-01

    Motor activity of the gastrointestinal tract is extensively controlled by the enteric nervous system (ENS). Numerous neurotransmitters and neuromodulators are responsible for this regulation. One of them is cocaine- and amphetamine-regulated transcript peptide (CART). So far, there are few reports available concerning the distribution, functions, and co-localization of CART in the human gastrointestinal tract. The aim of the present investigation was to study the distribution and degree of co-localization of CART with substances taking part in conducting sensory stimuli, such as: substance P (SP), neurokinin A (NKA), calcitonin gene related peptide (CGRP) and Leu 5 enkephalin (L-ENK) in the circular muscle layer of the human caecum. CART-like immunoreactive (CART-LI) nerve fibers formed a very dense meshwork in the circular muscle layer of the caecum in all patients studied. Moreover, all neuronal substances tested during the present investigation were observed in CART-LI processes, but the degree of co-localization depended on the type of substance. The highest number of CART-positive nerves also contained L-ENK. A slightly lower level of co-localization was observed in the case of CART and SP or NKA, while only single nerve fibers were simultaneously CART- and CGRP-positive.

  5. Immunohistochemical distribution of cocaine- and amphetamine-regulated transcript peptide - like immunoreactive (CART-LI) nerve fibers and various degree of co-localization with other neuronal factors in the circular muscle layer of human descending colon.

    Science.gov (United States)

    Gonkowski, Sławomir; Kamińska, Barbara; Landowski, Piotr; Całka, Jarosław

    2013-07-01

    Cocaine- and amphetamine-regulated transcript peptide (CART) is a neuromediator and/or neuromodulator in nerve structures within the gastrointestinal tract, but knowledge about its distribution, functions and co-localisation with other neuronal factors, especially in humans, is very scarce. During the present investigation the distribution and immunohistochemical reaction (IR) of CART - like immunoreactive (CART-LI) nerve fibers in the circular muscle layer of human descending colon were studied. Fragments of human colon were processed for double labelling immunofluorescence using a mixture of anti-CART antibodies with antibodies against vesicular acetylocholine transporter (VAChT), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase - activating peptide (PACAP), substance P (SP), galanin (GAL) and nitric oxide synthase (NOS). Thick CART-LI nerve fibers formed a very dense meshwork within the colonic circular muscle layer in all patients studied. The highest number of CART - positive nerves also contained VAChT and/or VIP. A slightly lower level of co-localisation was observed in the case of CART and PACAP or CART and NOS. Only single nerve fibers were concurrently immunoreactive to CART and SP or CART and GAL. The present study reports for the first time a detailed description of the IR of CART-LI nerve fibers in the circular muscle layer within adult human descending colon.

  6. Neuron-restrictive silencer factor (NRSF) represses cocaine- and amphetamine-regulated transcript (CART) transcription and antagonizes cAMP-response element-binding protein signaling through a dual NRSE mechanism.

    Science.gov (United States)

    Zhang, Jing; Wang, Sihan; Yuan, Lin; Yang, Yinxiang; Zhang, Bowen; Liu, Qingbin; Chen, Lin; Yue, Wen; Li, Yanhua; Pei, Xuetao

    2012-12-14

    Cocaine- and amphetamine-regulated transcript (CART) peptide plays a pivotal role in neuroprotection against stroke-related brain injury. However, the regulatory mechanism on CART transcription, especially the repression mechanism, is not fully understood. Here, we show that the transcriptional repressor neuron-restrictive silencer elements (NRSF, also known as REST) represses CART expression through direct binding to two NRSF-binding elements (NRSEs) in the CART promoter and intron 1 (named pNRSE and iNRSE, respectively). EMSA show that NRSF binds to pNRSE and iNRSE directly in vitro. ChIP assays show that NRSF recruits differential co-repressor complexes including CoREST and HDAC1 to these NRSEs. The presence of both NRSEs is required for efficient repression of CART transcription as indicated by reporter gene assays. NRSF overexpression antagonizes forskolin-mediated up-regulation of CART mRNA and protein. Ischemia insult triggered by oxygen-glucose deprivation (OGD) enhances NRSF mRNA levels and then NRSF antagonizes the CREB signaling on CART activation, leading to augmented cell death. Depletion of NRSF in combination with forskolin treatment increases neuronal survival after ischemic insult. These findings reveal a novel dual NRSE mechanism by which NRSF represses CART expression and suggest that NRSF may serve as a therapeutic target for stroke treatment.

  7. Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT(1A) receptor knockout mice: implications for schizophrenia.

    Science.gov (United States)

    van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally; Risbrough, Victoria B; Halberstadt, Adam L

    2011-01-01

    Serotonin-1A (5-HT(1A)) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT(1A) receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT(1A) receptor knockout mice display enhanced locomotor hyperactivity to acute treatment with amphetamine, a widely used animal model of hyperdopaminergic mechanisms in psychosis. In contrast, the effect of MK-801 on locomotor activity, modeling NMDA receptor hypoactivity, was unchanged in the knockouts. The effect of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) was markedly reduced in 5-HT(1A) receptor knockout mice. There were no changes in apomorphine-induced disruption of PPI, a model of sensory gating deficits seen in schizophrenia. Similarly, there were no major changes in density of dopamine transporters (DAT) or dopamine D(1) or D(2) receptors which could explain the behavioural changes observed in 5-HT(1A) receptor knockout mice. These results extend our insight into the possible role of these receptors in aspects of schizophrenia. As also suggested by previous studies using agonist and antagonist drugs, 5-HT(1A) receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain.

  8. 苯丙胺类兴奋剂所致精神障碍的临床诊治问题%Diagnosis and clinical management of amphetamine- induced psychosis

    Institute of Scientific and Technical Information of China (English)

    赵敏; 郝伟

    2011-01-01

    Psychosis induced by amphetamine-type stimulants (ATS) has become an important clinical challenge in psychiatric practice in China over recent years because of the rapid increase in the prevalence of ATS abuse. The authors introduce research on the genetic and pathological mechanisms underling ATS-induced psychosis and summarize findings on its clinical features, diagnosis and pharmacological treatment. They also discuss issues that need to be addressed in future research to increase understanding of ATS-induced psychosis and to improve the effectiveness of the clinical management of this condition.%近年国内苯丙胺类兴奋剂滥用日益严重,苯丙胺类兴奋剂所致精神障碍成为精神科临床的一个重要挑战.本文介绍了苯丙胺类兴奋剂所致精神障碍的分子遗传及病理机制方面的研究,并对其临床表现、诊断及药物治疗问题进行了综述,同时提出了未来研究的问题及方向.作者期望本文有助于深化读者对苯丙胺类兴奋剂所致精神障碍的了解及临床治疗疗效的提高.

  9. Determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxymethamphetamine in urine by online solid-phase extraction and ion-pairing liquid chromatography with detection by electrospray tandem mass spectrometry.

    Science.gov (United States)

    Wu, Ti-Yu; Fuh, Ming-Ren

    2005-01-01

    A method using an online solid-phase extraction (SPE) and ion-pairing liquid chromatography with electrospray tandem mass spectrometry (LC/ES-MS/MS) was developed for determination of amphetamine (Amp), methamphetamine (mAmp), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples. A SPE cartridge column with both hydrophilic and lipophilic functions was utilized for online extraction. A reversed-phase C18 LC column was employed for LC separation and MS/MS was used for detection. Trifluoroacetic acid was added to the mobile phase as an ion-pairing reagent. This method was fully automated and the extraction and analysis procedures were controlled by a six-port switch valve. Recoveries ranging from 85-101% were measured. Good linear ranges (10-500 ng/mL) for Amp and mAmp were determined. For MDA, MDMA and MDEA, dual linear ranges were obtained from 5-100 and 100-500 ng/mL, respectively. The detection limit of each analytical compound, based on a signal-to-noise ratio of 3, ranged from 1-3 ng/mL. The applicability of this newly developed method was examined by analyzing several urine samples from drug users. Good agreement was obtained between the results from this method and a literature GC/MS method.

  10. A quantitative, selective and fast ultra-high performance liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 33 basic drugs in hair (amphetamines, cocaine, opiates, opioids and metabolites).

    Science.gov (United States)

    Fernández, María Del Mar Ramírez; Di Fazio, Vincent; Wille, Sarah M R; Kummer, Natalie; Samyn, Nele

    2014-08-15

    Forensic testing for drugs of abuse in hair has become a useful diagnostic tool in determining chronic drug use as well as examining long-term drug history thorough segmental analysis. However, sensitive and specific analytical methods are needed. A simple, rapid and highly sensitive and specific method for the extraction and quantification of 33 opioids, opiates, cocaine, and amphetamines is presented. The method was fully validated according to international guidelines. Twenty milligrams of hair sample was pulverized and then incubated in the same disposable tube with methanol (under sonication at 45°C) during 4h. After centrifugation the supernatant was evaporated up to about 100 μL and a solid phase extraction (SPE) followed by separation and quantification using ultra performance liquid chromatography-tandem mass spectrometry (UHLC-MS/MS) were carried out. Chromatographic separation was achieved using a BEH phenyl column eluted with 0.1% formic acid: methanol (0.1% formic acid). Selectivity of the method was achieved by a combination of retention time, and two precursor-product ion transitions. Good intra-assay and inter-assay precision (relative standard deviations (RSDs) were observed (hair samples obtained from forensic and toxicology cases and to proficiency test (obtaining z-scores lower than 1 for most of the compounds). The validation and actual sample analysis results show that this method is rugged, precise, accurate, and well-suited for routine hair analysis.

  11. 尿液中苯丙胺类毒品残留的MISPE-高效液相色谱法测定%Simultaneous determination of amphetamine homologues in urine by high-performance liquid chromatography with molecularly imprinted solid-phase extraction

    Institute of Scientific and Technical Information of China (English)

    陈琦君; 朱波; 金米聪

    2013-01-01

    Objective:To develop a method for the simultaneous deter mination of amphetamine homologues,such as methamphetamine (MA),amphetamine (AM),3,4-methylenedioxy-N-methamphetamine (MDMA),3,4-methylenedioxy-amphetamine (MDA) and 3-methoxy-4,5-methylenedioxy-amphetamine (MMDA) in urine by high-performance liquid chromatography with molecularly imprinted solid-phase extraction (MISPE).Methods:After the urine samples were mixed with 100 mmol/L ammonium acetate buffer (pH8.0) and centrifuged at 8000 rpm,the cleanup procedure was optimized on an activating MISPE cartridge with 1.0% acetate acid/acetonitrile (1/99,v/v) as elution.The separation was performed on an XBridge RP18 column by a mobile phase consisting of methanol-acetonitrile-100 mmol/L ammonium acetate solution for gradient elution.Detection was carried out by an ultraviolet detector at 215 nm.Results:Calibration curves of the five amphetamine homobgues were linear within the range of 0.05 mg/L ~ 15.0 mg/L with correlation coefficients more than 0.999.The limits of quantification (LOQs) were between 0.017 mg/L ~ 0.03 mg/L.The extraction recoveries were between 88.0% ~ 98.8%,and the RSDs were less than 5.0%.Conclusion:This developed method is simple,sensitive and accurate.It is suitable for the detection of the amphetamine homologue residues in biological specimens from drug users.%目的:建立快速、准确的尿液中甲基苯丙胺(MA)、苯丙胺(AM)、3,4-亚甲基二氧基甲基苯丙胺(MDMA)、3,4-亚甲基二氧基苯丙胺(MDA)、3-甲氧基-4,5-亚甲基二氧基苯丙胺(MMDA)残留的分子印迹固相萃取(MISPE)高效液相色谱测定方法.方法:尿液经与醋酸铵缓冲液(pH 8.0)混合后通过离心分离(8000 rpm),上清液采用预先活化的分子印迹固相萃取小柱净化,以1.0%醋酸/乙腈(1/99,v/v)溶液进行洗脱,在XBridge RP18色谱柱上,以甲醇-乙腈-100 mmol/L醋酸铵水溶液为流动相进行梯度洗脱,采用215 nm波长进行检测.结果:MA

  12. 分子印迹固相萃取法在血中苯丙胺类毒品分析中的应用%Application of molecularly imprinted solid-phase extraction for separating and assaying amphetamines in blood samples

    Institute of Scientific and Technical Information of China (English)

    常靖; 朱军; 邸玉敏; 张雷萍; 崔巍; 郝红霞; 于忠山

    2011-01-01

    Objecive A method for extraction of amphetamines in blood samples using molecularly imprinted solid phase extraction and gas chromatography-mass spectrometry(GC/MS). Methods Human blood samples were spiked with amphetamine,methamphetamine, MDA and MDMA ,and diluted with 4:1 (v/v)with 10mmol/L ammonium acetate buffer( pH8.0); activating the MIP column with 1 mL methanol and 1mL 10mmol/L ammonium acetate( pH8. 0); Washing the impurities using 2 1 mL water, 1 mL 60/40 MeCN/water and 1 mL 1% HAc in MeCN; Elute the amphetamine drugs with 2 1mL 1% formic acid in methanol, then evaporate under nitrogen to dryness and reconstitute with 100μ L methanol prior to GC/MS analysis. Results The recoveries obtained with this method for amphetamine drugs are more than 90%. The linear range was 20 ~ 5000ng/mL with correlation coefficients between 0. 995 7 and 0. 998 9. The limits of detection were 20ng/mL for amphetamine ( AM ) , 16ng/mL methamphetamine ( MA ), 30ng/mL methylenedioxyamphetamine (MDA) and methylened ioxy methamp hetamine(MDMA) ,The limits of quantitative were 10ng/mL for AM,8ng/mL for methamphetamine(MAM), 15ng/mL for MDA and MDMA. Conclusion Recoveries are higher,impurities were less. The method could be applied for simultaneous determination of trace amphetamines in biological specimens.%目的 建立分子印迹固相萃取(MISPE)、GC/MS分析方法,用于血液中苯丙胺类毒品检测.方法 10mmol/L醋酸铵缓冲液(pH8.0)4倍稀释空白添加血液,1mL甲醇,1mL 10mmol/L醋酸铵缓冲液(pH8.0)活化苯丙胺类分子印迹固相萃取柱;2×1mL去离子水、1mL 60%的乙腈去离子水、1mL 1%醋酸乙腈洗涤杂质;2×1mL 1%甲酸/甲醇洗脱,洗脱液挥干定容,经GC/NPD、GC/MS分析检测.结果 各种苯丙胺类毒品回收率均在90%以上,在20~5000ng/mL浓度范围内线性关系良好,r2为0.9957~0.9989,LOQ在16~30ng/mL之间,LOD在8~15ng/mL之间.结论 本方法回收率高,净化效果显著,稳定性好,杂质干

  13. SPE/UPLC法检测血中吗啡、苯丙胺类及氯胺酮%The simultaneous analysis of morphine,amphetamines and ketamine in whole blood by SPE/UPLC

    Institute of Scientific and Technical Information of China (English)

    张小婷; 孙立敏; 刘娟; 徐淑云

    2011-01-01

    Objective To establish a solid phase extraction (SPE)/UPLC method for the determination of morphine,amphetamines and ketamine in whole blood simultaneously. Methods Morphine, MA, MDMA,MDA,ketamine were extracted from whole blood using Agilent SCX 3cc (60mg)extraction cartridges and detected by UPLC-PDA. Qualitative and quantitative analysis was obtained by retention time and UVspectrum. Results The recoveries for morphine, MA, MIDMA, MDA, ketamine were 81. 4% ± 2. 51%,88.2% ±2.48% ,91. 8% ± 2.03% ,93. 8% ± 1.46% ,74. 8% ± 2. 27% respectively, The correlation coefficient of linear calibration curve was over 0. 999 within concentration range 0.08 ~ 100μg/mL,0.4 ~100μg/mL,0.2 ~ 75 μg/ml,0.3 ~ 75 μg/mL, 0.4 ~ 100 μg/mL respectively. The limits of qualification were 30pg,200pg, 80pg, 100pg, 200pg respectively. Conclusion The method was simple, rapid and accurate for qualitative and quantitative analysis of morphine,amphetamines, ketamine in whole blood simultaneously.%目的 建立SPE/UPLC方法在同一条件下同时检测血中吗啡、苯丙胺类及氯胺酮.方法 采用SCX 3cc(60mg)固相萃取柱萃取血中吗啡、MA、MDMA、MDA及氯胺酮,用超高效液相色谱(UPLC)-二极管阵列检测器(PDA)检测,结合保留时间和紫外光谱进行定性、定量分析,对实验各环节进行优化,并进行实际案例检测.结果 吗啡、MA、MDMA、MDA、氯胺酮的固相萃取提取回收率分别为81.4%±2.51%、88.2%±2.48%、91.8%±2.03%、93.8%±1.46%、74.8%±2.27%,峰面积和质量浓度的线性关系良好(r>0.999),线性范围分别为0.08~100μg/mL、0.4~100μg/mL、0.2~75μg/mL、0.3~75μg/mL、0.4~100μg/mL,检出限分别为30pg、200pg、80pg、100pg、200pg.结论 本文所建方法适用于血中吗啡、苯丙胺类、氯胺酮常见毒品的筛选及定量分析.

  14. Current state and prospect of pharmacological approaches to amphetamine-type stimulants dependence%苯丙胺类依赖的药物治疗现状和展望

    Institute of Scientific and Technical Information of China (English)

    崔巍; 沈雯雯; 周文华; 韩怡凡

    2012-01-01

    笨丙胺类药物是国内第二大成瘾性药物,苯丙胺类依赖是一个重要的公共健康问题,但至今尚未发现有效的治疗药物.本文首先介绍了苯丙胺类依赖形成的多巴胺和非多巴胺机制,并对多巴胺转运体抑制剂、多巴胺受体部分激动剂及拮抗剂、谷氨酸受体拮抗剂、乙酰胆碱酯酶抑制剂、γ-氧基丁酸受体激动剂、5-羟色胺转运体抑制剂以及阿片受体拮抗剂等已用于苯丙胺类依赖治疗实践的药物进行了系统综述,并展望了苯丙胺类依赖治疗药物的研究方向.%Amphetamine-type stimulants ( ATS) are the second most widely used addictive drugs in China. ATS dependence has become a serious public heath problem. Currently, there is no pharmacological treatment with established efficacy for inhibiting this addictive disorder. Changes of non-dopaminergic systems implicated in ATS dependence, such as GABAergic, cholinergic and glutamatergic systems, suggest that this addictive disorder be treated with drugs targeting either the dopaminergic system or non-dopaminergic system. This paper reviews pharmacological candidates, including the inhibitors of dopamine and serotonin transporters, the partial agonists of do-pamine receptors, the antagonists of glutamate receptor, and the inhibitors of acetylcholinesterase, which might be useful in the treatment of ATS dependence based on preclinical data. The prospect of novel anti-ATS dependence drugs being developed is also discussed.

  15. 苯丙胺类兴奋剂所致精神障碍者临床特征及危险因素分析%CLINICAL CHARACTERISTICS AND RISK FACTORS OF AMPHETAMINE-TYPE STIMULANT-INDUCED PSYCHOSIS

    Institute of Scientific and Technical Information of China (English)

    赵燕; 江海峰; 杜江; 任其欢; 李煦; 汪文文; 孙海明; 赵敏

    2014-01-01

    目的:探讨苯丙胺类兴奋剂(amphetamine-type stimulant,ATS)所致精神障碍患者的临床特征及危险因素.方法:采用横断面研究,收集了355例ATS滥用/依赖者的临床资料,其中符合ATS所致精神障碍者181例.结果:ATS滥用/依赖者以男性、低学历、无业及单身者居多.与无精神障碍的患者相比,有精神障碍组首次吸毒年龄较低、ATS依赖者和多药滥用者比例较高、吸毒剂量较高和过去1月中吸毒天数较多(P<0.01).多因素分析结果显示,存在ATS依赖的OR值为5.813(95% CI=3.655-10.231,P<0.01),多药滥用的OR值为2.262 (95%CI=1.309-3.727,P<0.01).结论:精神障碍患者的药物滥用程度较无精神障碍的患者更为严重.因此,在临床诊治中应重点预防药物滥用程度严重者的精神障碍的发生,尤其是依赖者及多药滥用者,以减少药物滥用所带来的损害.

  16. High performance liquid chromatography-high resolution mass spectrometry and micropulverized extraction for the quantification of amphetamines, cocaine, opioids, benzodiazepines, antidepressants and hallucinogens in 2.5 mg hair samples.

    Science.gov (United States)

    Favretto, Donata; Vogliardi, Susanna; Stocchero, Giulia; Nalesso, Alessandro; Tucci, Marianna; Ferrara, Santo Davide

    2011-09-23

    A high performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) method for simultaneous screening and quantification of 28 drugs was developed and validated for 2.5 mg hair samples. Target drugs and their metabolites included amphetamines, cocaine, opioids, benzodiazepines, antidepressants, and hallucinogens. After decontamination, hair samples were extracted with 200 μL of a mixture of water: acetonitrile:1 M trifluoroacetic acid (80:10:10, v/v) using a 5 min simultaneous pulverization/extraction step. The extracts were analysed by HPLC-HRMS in an Orbitrap at a nominal resolution of 60,000, with concomitant in source collisional experiments (in source CID). Gradient elution on an Atlantis T3 column resolved 28 target compounds and 5 internal standards. Total chromatographic run time was 26 min. Calibration was achieved by linear regression analysis utilizing six calibration points; R2 ranged from 0.9964 to 0.9999, the limits of quantification were 0.1 ng/mg for 8 compounds, 0.2 ng/mg for 16 compounds and 0.5 ng/mg for 4 compounds; mean relative errors from -21% to +23% were obtained; relative standard deviation, used to estimate repeatability and intermediate reproducibility at three concentrations, was always less than 20%. Process efficiency and recoveries for all analytes were better than 65 and 73%, respectively, at any concentration. The method was applied to hair samples from forensic investigations that contained a broad assortment of drugs of abuse and pharmaceuticals. The use of concomitant HRMS full scan and CID afforded the possibility of retrospective analysis for discovering untargeted drugs.

  17. Simultaneous detection and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates in hair by LC-ESI-MS-MS using a single extraction method.

    Science.gov (United States)

    Miller, Eleanor I; Wylie, Fiona M; Oliver, John S

    2008-09-01

    A liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous identification and quantification of amphetamines, diazepam and its metabolites, cocaine and its metabolites, and opiates from hair using a single extraction method. As part of the method development, Gemini C18, Synergi Hydro RP, and Zorbax Stablebond-Phenyl LC columns were tested with three different mobile phases. Analyte recovery and limit of detection were evaluated for two different solid-phase extraction methods that used Bond Elut Certify and Clean Screen cartridges. Phosphate buffer (pH 5.0) was chosen as the optimum hair incubation medium because of the high stability of cocaine and 6-monoacetylmorphine using this method and faster sample preparation.