WorldWideScience

Sample records for amphetamines

  1. Substance use -- amphetamines

    Science.gov (United States)

    ... illegally): dexies, kiddie-speed, pep pills, uppers; black beauty (when combined with amphetamine) Methamphetamine (crystal solid form): ... verify that A.D.A.M. follows rigorous standards of quality and accountability. A.D.A.M. ...

  2. Amphetamine margin in sports

    Energy Technology Data Exchange (ETDEWEB)

    Laties, V.G.; Weiss, B.

    1981-10-01

    The amphetamines can enhance athletic performance. That much seem clear from the literature, some of which is reviewed here. Increases in endurance have been demonstrated in both humans and rats. Smith and Beecher, 20 years ago, showed improvement of running, swimming, and weight throwing in highly trained athletes. Laboratory analogs of such performances 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.

  3. 78 FR 67365 - Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine...

    Science.gov (United States)

    2013-11-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-1361] Determination That Adderall (Amphetamine Aspartate; Amphetamine Sulfate; Dextroamphetamine Saccharate... No. Drug Applicant NDA 011522 ADDERALL Teva Womens Health (amphetamine Inc., 41 Moores aspartate; Rd...

  4. Detection of amphetamine following administration of fenproporex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    1996-10-01

    Drugs that are metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive drug testing results. A number of different compounds have been reported to produce amphetamine in the urine of users. One of these compounds, fenproporex, has been shown to produce amphetamine. Previous reports indicate that the parent compound can be detected only for a few hours following administration, whereas the amphetamine can be detected for several days. Administration of fenproporex to five healthy volunteers resulted in amphetamine being detected in the urine of all subjects. Peak concentrations of amphetamine were detected at approximately 6-20 h postdose and ranged from approximately 1200 to 2100 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine for up to 119 h. Analysis of the metabolically produced amphetamine showed the presence of both enantiomers, which can be helpful in the differentiation of some illicit amphetamine use from the use of this precursor drug. More significantly, all samples that contained amphetamine at a concentration of at least 500 ng/mL were shown to also contain measurable amounts of the parent compound.

  5. The prognosis following amphetamine poisoning

    DEFF Research Database (Denmark)

    Horwitz, Henrik; Dalhoff, Kim P.; Klemp, Marc

    2017-01-01

    the background population. Results: From August 2006 to December 2013 we identified 1444 patients (70% males) who experienced amphetamine poisoning; 52% of the cases were classified as mixed poisonings and the average age at first contact was 24.8 years (SD 8.6). The prevalence of psychiatric disorders, HIV...

  6. Stimulant ADHD Medications -- Methylphenidate and Amphetamines

    Science.gov (United States)

    ... prescription stimulants? dextroamphetamine (Dexedrine ® ) dextroamphetamine/amphetamine combination product (Adderall ® ) methylphenidate (Ritalin ® , Concerta ® ). Popular slang terms for prescription ...

  7. Metabolic Precursors to Amphetamine and Methamphetamine.

    Science.gov (United States)

    Cody, J D

    1993-12-01

    Analysis and interpretation of amphetamine results is a challenging process made difficult by a number of factors. One of the complications comes from determination of the origin of amphetamine or methamphetamine in a sample. Given the relatively rare occasions that either of these two drugs are prescribed, legal prescription of one of these drugs is seldom a reason for positive findings. A number of other precursor compounds are metabolized by the body to amphetamine or methamphetamine, many of which could be used for legitimate reasons. Fourteen different metabolic precursors of amphetamine or methamphetamine are included in this review. They are amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Medical use, metabolism, analysis, and interpretation are described to afford sufficient information to evaluate the possible involvement of these drugs in positive amphetamine or methamphetamine results. Copyright © 1993 Central Police University.

  8. Amphetamine enhances endurance by increasing heat dissipation.

    Science.gov (United States)

    Morozova, Ekaterina; Yoo, Yeonjoo; Behrouzvaziri, Abolhassan; Zaretskaia, Maria; Rusyniak, Daniel; Zaretsky, Dmitry; Molkov, Yaroslav

    2016-09-01

    Athletes use amphetamines to improve their performance through largely unknown mechanisms. Considering that body temperature is one of the major determinants of exhaustion during exercise, we investigated the influence of amphetamine on the thermoregulation. To explore this, we measured core body temperature and oxygen consumption of control and amphetamine-trea ted rats running on a treadmill with an incrementally increasing load (both speed and incline). Experimental results showed that rats treated with amphetamine (2 mg/kg) were able to run significantly longer than control rats. Due to a progressively increasing workload, which was matched by oxygen consumption, the control group exhibited a steady increase in the body temperature. The administration of amphetamine slowed down the temperature rise (thus decreasing core body temperature) in the beginning of the run without affecting oxygen consumption. In contrast, a lower dose of amphetamine (1 mg/kg) had no effect on measured parameters. Using a mathematical model describing temperature dynamics in two compartments (the core and the muscles), we were able to infer what physiological parameters were affected by amphetamine. Modeling revealed that amphetamine administration increases heat dissipation in the core. Furthermore, the model predicted that the muscle temperature at the end of the run in the amphetamine-treated group was significantly higher than in the control group. Therefore, we conclude that amphetamine may mask or delay fatigue by slowing down exercise-induced core body temperature growth by increasing heat dissipation. However, this affects the integrity of thermoregulatory system and may result in potentially dangerous overheating of the muscles. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  9. Urethralism concomitant with amphetamine abuse

    Directory of Open Access Journals (Sweden)

    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.

  10. Neurotoxicity of drugs of abuse - the case of methylenedioxy amphetamines (MDMA, ecstasy ), and amphetamines

    OpenAIRE

    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 ecsta...

  11. Amphetamines

    Science.gov (United States)

    ... meth mouth") when using methamphetamine mood disturbances and delusions similar to those felt by people with bipolar ... Drug Problem. What Should I Do? School Counselors Cocaine Methamphetamine (Meth) Ketamine Drugs: What to Know View ...

  12. Amphetamine

    Science.gov (United States)

    ... for ADHD, which may include counseling and special education. Make sure to follow all of your doctor's ... of an arm or leg motor or verbal tics believing things that are not true feeling unusually ...

  13. 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

  14. Clobenzorex: evidence for amphetamine-like behavioral actions.

    Science.gov (United States)

    Young, R; Darmani, N A; Elder, E L; Dumas, D; Glennon, R A

    1997-02-01

    Clobenzorex, an optically active N-substituted derivative of (+)amphetamine, has been identified on the illicit market. Because so little is known regarding the pharmacology or abuse potential of this agent, it was examined in tests of stimulus generalization in rats trained to discriminate 1 mg/kg of (+)amphetamine from vehicle to determine if it would produce amphetamine-appropriate responding. Clobenzorex (ED50 = 6.6 mg/kg) substituted for (+)amphetamine (ED50 = 0.3 mg/kg) but was approximately twenty times less potent than the training drug. Clobenzorex was also compared with (+)amphetamine and cocaine for its ability to induce locomotor stimulation and rearing frequency in mice. Clobenzorex was active in both assays but was less potent than either (+)amphetamine or cocaine. It is concluded that, although weaker than (+)amphetamine, clobenzorex constitutes an agent with amphetamine-like central stimulant behavioral properties.

  15. Metabolic production of amphetamine following administration of clobenzorex.

    Science.gov (United States)

    Valtier, S; Cody, J T

    1999-01-01

    Many of the anorectic drugs that are metabolized to amphetamine and/or methamphetamine pose significant concerns in the interpretation of amphetamine-positive drug testing results. One of these drugs--clobenzorex--has been shown to produce amphetamine. Thirty milligrams of clobenzorex hydrochloride, in the form of a single Asenlix capsule (Roussel, Mexico), were administered orally to five human volunteers with no history of amphetamine, methamphetamine or clobenzorex use. Following administration, urine samples (total void volume) were collected ad lib for seven days and pH, specific gravity and creatinine values were determined. To determine the excretion profile of amphetamine and parent drug, samples were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS) using a standard amphetamine procedure with additional monitoring of ions at m/z 91, 118, 125 and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were detected at 4 to 19 h postdose and ranged from approximately 715 to 2474 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine in one subject for up to 116 h postdose. GC/MS was also used to determine the enantiomeric composition of the metabolite, amphetamine. This analysis revealed the metabolically derived amphetamine was only the d-enantiomer. This differs from previous literature which indicates clobenzorex is the racemic N-orthochlorobenzyl derivative of amphetamine.

  16. Amphetamine and fenproporex levels following multidose administration of fenproporex.

    Science.gov (United States)

    Cody, J T; Valtier, S; Stillman, S

    1999-01-01

    Drugs that are metabolized to amphetamine or methamphetamine are potentially of significant concern in the interpretation of positive drug-testing results for amphetamines. A number of different drugs have been reported to produce amphetamine in the urine of users. One of these compounds, fenproporex, has been shown to be metabolized to amphetamine, and previous reports indicated the parent compound could be detected at low levels for up to 48 h. Administration of fenproporex for seven days (one 10-mg dose per day) to five healthy volunteers resulted in amphetamine being detected in the urine of all subjects. Peak concentrations of amphetamine ranged from approximately 2850 to 4150 ng/mL. Amphetamine could be detected (> or = 5 ng/mL) in the urine for up to nearly 170 h after the last dose. Analysis of the metabolically produced amphetamine showed the presence of both enantiomers, which can be helpful in the differentiation of some illicit amphetamine use from the use of this precursor drug. In addition, evaluation of the enantiomeric composition of the metabolite (amphetamine) can be a valuable tool in the interpretation of time since last dose. More significantly, all samples that contained amphetamine at a concentration of > or = 500 ng/mL were shown to also contain detectable amounts of the parent compound.

  17. physiological effects of the amphetamines during exercise

    African Journals Online (AJOL)

    PHYSIOLOGICAL EFFECTS OF THE AMPHETAMINES DURING EXERCISE* c. H. WYNDHAM, G. G. ROGERS, A. J. S. BENADE AND N. B. STRYDOM, Human Sciences Laboratory, Chamber of. Mines of SOUTh Africa, Johannesburg. SUMMARY. Oxygen consumption, heart rate, minute ventilation and blood lactate were ...

  18. Adderall® (amphetamine-dextroamphetamine) toxicity.

    Science.gov (United States)

    Fitzgerald, Kevin T; Bronstein, Alvin C

    2013-02-01

    The American Psychiatric Association estimates that 3-7% of US school-aged children exhibit attention-deficit/hyperactivity disorder (ADHD). Adderall(®) (amphetamine dextroamphetamine) and a variety of brand names and generic versions of this combination are available by prescription to treat ADHD and narcolepsy. Both immediate and sustained release products are used as are single agent amphetamine medication. Knowing the exact agent ingested can provide information of dose labeled and length of clinical effects. These drugs are used off label by college students for memory enhancement, test taking ability, and for study marathons. These agents are DEA Schedule II controlled substances with high potential for abuse. For humans with ADHD or narcolepsy, standard recommended dosage is 5-60 mg daily. Amphetamine and its analogues stimulate the release of norepinephrine affecting both α- and β-adrenergic receptor sites. α-Adrenergic stimulation causes vasoconstriction and an increase in total peripheral resistance. β-Adrenergic receptor stimulation leads to an increase in heart rate, stroke volume, and skeletal muscle blood flow. Clinical signs of Adderall(®) overdose in humans and dogs include hyperactivity, hyperthermia, tachycardia, tachypnea, mydriasis, tremors, and seizures. In addition, Adderall intoxication in dogs has been reported to cause hyperthermia, hypoglycemia, hypersegmentation of neutrophils, and mild thrombocytopenia. Diagnosis can be confirmed by detecting amphetamine in stomach contents or vomitus, or by positive results obtained in urine tests for illicit drugs. Treatment is directed at controlling life-threatening central nervous system and cardiovascular signs. Seizures can be controlled with benzodiazepines, phenothiazines, pentobarbital, and propofol. Cardiac tachyarrhythmias can be managed with a β-blocker such as propranolol. Intravenous fluids counter the hyperthermia, assist in maintenance of renal function, and help promote the

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

    OpenAIRE

    Grund, Jean-Paul; Coffin, Philip; Jauffret-Roustide, Marie; Dijkstra, Minke; Bruin, Dick; 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 effects, including amphetamine, methamphetamine, methcathinone and cathinone and referred to as ‘amphetamines’ in this review (Holman, 1994). MDMA (3,4-methylenedioxy-N-methamphetamine or ecstasy) is a ...

  20. Chirality of methamphetamine and amphetamine from workplace urine samples.

    Science.gov (United States)

    Cooke, B J

    1994-01-01

    Several positive methamphetamine/amphetamine urine samples were reexamined to determine the chirality of the detected drug or drugs. (S)-N-(Trifluoroacetyl)prolyl derivatives were prepared and analyzed using GC/MS. In one case, pure d-isomers of methamphetamine and amphetamine were detected. In the remainder of the samples involving both drugs, skewed racemates were detected, with the l-isomer of methamphetamine and the d-isomer of amphetamine predominating slightly over their enantiomers. In samples involving amphetamine only, 50:50 mixtures of d- and l-isomers were detected. In no instance was pure i-methamphetamine (from a Vicks inhaler) detected.

  1. The expression of amphetamine sensitization is dissociable from anxiety and aversive memory: Effect of an acute injection of amphetamine.

    Science.gov (United States)

    Gatica, Rafael Ignacio; Pérez-Valenzuela, Enzo; Sierra-Mercado, Demetrio; Fuentealba, José Antonio

    2017-01-18

    The repeated administration of amphetamine can lead to locomotor sensitization. Although the repeated administration of amphetamine has been associated with anxiety and impaired working memory, it is uncertain if expression of amphetamine sensitization is associated with modifications of emotional memories. To address this issue, rats were injected once daily with amphetamine for five consecutive days (1.5mg/kg). After four days of withdrawal, rats were delivered an acute amphetamine injection to assess the expression of sensitization. A single exposure to an elevated plus maze (EPM), 24h after the last injection of amphetamine, showed that amphetamine sensitization is not accompanied by anxiety. Next, aversive memory was assessed using an 11day inter-trial interval between the EPM Trial 1 and EPM Trial 2. Rats administered with saline showed a percentage of open arms time (% OAT) in Trial 2 that was comparable to Trial 1, demonstrating a reduction in the retrieval of aversive memory. However, rats sensitized after the EPM Trial 1 showed a significant decrease in the % OAT in Trial 2. Importantly, a decrease in the % OAT in Trial 2 compared to Trial 1 was also observed after a single injection of amphetamine 24h before Trial 2. These results show a facilitation in the retrieval of aversive memory, and suggest that a previous amphetamine injection is enough to produce a protracted activation of neural circuits necessary for the retrieval of aversive memory. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Destruction of amphetamine in aqueous solution using gamma irradiation

    Science.gov (United States)

    Alkhuraiji, Turki S.; Ajlouni, Abdul-Wali

    2017-10-01

    Amphetamine-type stimulants are among the most prevalent and widespread commonly abused drugs. Amphetamine and its derivatives were detected in aquatic environment. This study aimed to demonstrate experimentally the ability of γ-irradiation combined with persulfate anions (S2O82-) to degrade and mineralize the amphetamine in aqueous solution. An initial amphetamine concentration of 125 μM in distilled water was completely degraded by a γ-ray dose of 2.8 kGy. Generation of the sulfate radical (SO4•-) from the fast reaction of added S2O82- with hydrated electrons (eaq-; keaq-/S2O82- = 1.1×1010 M-1 s-1) improved the efficiency of amphetamine degradation and mineralization. A γ-ray dose of 0.667 and 0.350 kGy in the absence and presence of S2O82- anions degraded 90% of the amphetamine, respectively. For γ-ray/free O2 and γ-ray/S2O82- systems, 11.5 and 7 kGy was required for 50% amphetamine mineralization, respectively. Addition of HCO3- anions lowered the amphetamine degradation yield, whereas N2 gas, SO42-, and Cl- anions had a negligible effect.

  3. Detection and diagnostic interpretation of amphetamines in hair.

    Science.gov (United States)

    Nakahara, Y

    1995-01-05

    A review with 22 references on detection and incorporation of amphetamines in hair is presented. This review deals with the detection, incorporation into hair, behavior in the hair shaft, confirmation of past drug use and diagnosis of dependence mainly regarding amphetamine and methamphetamine, along with methoxyphenamine, methylenedioxymethamphetamine, bromomethamphetamine, deprenyl, benzphetamine, fenproporex and mefenorex. First, pretreatment, extraction and analytical methods for amphetamines in hair using immunoassay, HPLC and GC/MS are discussed. This is followed by sections describing the animal experiments, incorporation rates of amphetamines from blood to hair and relationship between drug history and drug distribution in hair. Finally, the diagnosis of amphetamine dependence and confirmation of methamphetamine baby by hair analysis is discussed. The paper concludes with a brief outlook.

  4. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit

    2014-01-01

    to amphetamine was markedly reduced. Our findings demonstrate that amphetamine requires the presence of αCaMKII to elicit a full-fledged effect on DAT in vivo: αCaMKII does not only support acute amphetamine-induced dopamine efflux but is also important in shaping the chronic response to amphetamine....

  5. 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.

  6. Metabolic production of amphetamine following multidose administration of clobenzorex.

    Science.gov (United States)

    Baden, K L; Valtier, S; Cody, J T

    1999-10-01

    The interpretation of urine drug-testing results can have important forensic and legal implications. In particular, drugs that are metabolized to amphetamine or methamphetamine or both pose significant concerns. In this study, clobenzorex, an anorectic drug that is metabolized to d-amphetamine, was administered to five subjects. Each subject took 30 mg daily for seven days, and individual urine samples were collected ad lib for 14 days beginning on the first day the drug was administered. Urine pH, specific gravity, and creatinine values were determined for each sample. Gas chromatography-mass spectrometry (GC-MS) was used to determine the excretion profile of amphetamine and clobenzorex using a standard procedure for amphetamines with additional monitoring of ions at m/z 118, 125, and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were found at 82 to 168 h after the first dose and ranged from approximately 2900 to 4700 ng/mL amphetamine. The use of a regioisomer (3-Cl-benzylamphetamine) as internal standard allowed for accurate quantitation of the parent drug. Peak concentrations of clobenzorex were found at 50 to 120 h after the first dose and ranged from approximately 8 to 47 ng/mL clobenzorex. However, in many samples, clobenzorex was not detected at all. This analysis revealed that the metabolite, (amphetamine) is present in much higher concentrations than the parent compound, clobenzorex. Yet even at peak amphetamine concentrations, the parent was not always detected (limit of detection 1 ng/mL). Thus, in the interpretation of amphetamine-positive drug-testing results, the absence of clobenzorex in the urine sample does not exclude the possibility of its use.

  7. Amphetamines and pH-shift agents for brain imaging

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book gives a review of the results of experimental and clinical research on both I-amphetamine derivatives and pH-shift agents. Virtually all relevant working groups from the USA and Europe have contributed to this volume. The pharmacology of amphetamine and the corresponding receptor theories are described in detail, whereas other chapters deal with the labeling as well as the metabolic process of this drug. In addition to this, new amphetamine derivatives are presented together with other essential products which play a significant role in scintigraphy of the brain function. Finally, there are two chapters on instrumentation problems followed by eight contributions on the clinical results of amphetamine scintigraphy in cerebral vascular diseases, epilepsy, migraine and brain tumors.

  8. Illegal or legitimate use? Precursor compounds to amphetamine and methamphetamine.

    Science.gov (United States)

    Musshoff, F

    2000-02-01

    The interpretation of methamphetamine and amphetamine positive test results in biological samples is a challenge to clinical and forensic toxicology for several reasons. The effects of pH and dilution of urine samples and the knowledge about legitimate and illicit sources have to be taken into account. Besides a potentially legal prescription of amphetamines, many substances metabolize to methamphetamine or amphetamine in the body: amphetaminil, benzphetamine, clobenzorex, deprenyl, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, and prenylamine. Especially the knowledge of potential origins of methamphetamine and amphetamine turns out to be very important to prevent a misinterpretation of the surrounding circumstances and to prove illegal drug abuse. In this review, potential precursor compounds are described, including their medical use and major clinical effects and their metabolic profiles, as well as some clues which help to identify the sources.

  9. Amphetamine, past and present--a pharmacological and clinical perspective.

    Science.gov (United States)

    Heal, David J; Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-06-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine's diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine's distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed.

  10. Stereoselectivity of the TDxADx/FLx Amphetamine/Methamphetamine II amphetamine/methamphetamine immunoassay--response of urine specimens following nasal inhaler use.

    Science.gov (United States)

    Poklis, A; Moore, K A

    1995-01-01

    The TDxADx/FLx Amphetamine/Methamphetamine II fluorescence polarization immunoassay (Abbott Diagnostic) for the detection of amphetamine and methamphetamine in urine was evaluated for stereoselectivity and response to specimens collected following as recommended and double the recommended dose use of Vicks Nasal Inhaler. The assay is calibrated with d-amphetamine, at cutoff concentration of 300 ng/mL for a positive response. Cross-reactivity studies demonstrated a positive result with 1000 ng/mL l-amphetamine, 300 ng/mL d-methamphetamine, and approximately 2000 ng/mL desoxyephedrine. A good correlation was observed between urines obtained following ingestion of d-amphetamine simultaneously analyzed by TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry: r2 = 0.954, N = 100. However, urine obtained following ingestion of racemic methamphetamine showed no correlation between TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry results: r2 = 0.420, N = 28. Urines collected following as recommended use for five consecutive days of Vicks Nasal Inhaler containing l-desoxyephedrine did not yield positive TDxADx/FLx Amphetamine/Methamphetamine II results. Only two urines from a subject using twice the recommended inhaler dose yielded positive TDxADx/FLx Amphetamine/Methamphetamine II results. These urines contained 1560 and 1530 ng/mL desoxyephedrine when analyzed by gas chromatography/mass spectrometry. Greater than recommended use of Vicks Nasal Inhaler may yield false positive TDxADx/FLx Amphetamine/Methamphetamine II results for amphetamine use when calibrated at 300 ng/mL d-amphetamine. If calibrated at 1000 ng/mL, d-amphetamine, the TDxADx/FLx Amphetamine/Methamphetamine II is unlikely to yield false positive results for amphetamine, even following excessive inhaler use.

  11. Combined effects of modafinil and d-amphetamine in male Sprague-Dawley rats trained to discriminate d-amphetamine.

    Science.gov (United States)

    Quisenberry, Amanda J; Prisinzano, Thomas; Baker, Lisa E

    2013-09-01

    Modafinil is a novel wake-promoting drug with FDA approval for the treatment of sleep-related disorders that has recently been investigated as a potential agonist replacement therapy for psychostimulant dependence. Previous research in animals and humans indicates modafinil has a lower abuse liability than traditional psychostimulants, although few studies have carefully assessed modafinil's stimulus properties in combination with other psychostimulants. The current study trained male Sprague-Dawley rats to discriminate subcutaneous injections of 0.3 mg/kg (n=8) or 1.0 mg/kg d-amphetamine (n=8) from saline under an FR 20 schedule of food reinforcement and substitution tests were administered with d-amphetamine (0.03-1.0 mg/kg, s.c.), modafinil (32-256 mg/kg, i.g.), and a low modafinil dose (32 mg/kg, i.g.) in combination with d-amphetamine (0.03-1.0 mg/kg, s.c.) to determine if these drugs have additive effects. The selective D2 dopamine agonist, PNU-91356A, was also tested as a positive control and ethanol and morphine were tested as negative controls. Results indicate that modafinil produced dose-dependent and statistically significant d-amphetamine-lever responding in both groups and nearly complete substitution in animals trained to discriminate 1.0 mg/kg d-amphetamine. Modafinil pretreatment slightly increased the discrimination of low d-amphetamine doses in animals trained to discriminate 0.3 mg/kg d-amphetamine. These results support previous findings that modafinil and d-amphetamine may have additive effects. In consideration of recent interests in modafinil as an agonist treatment for psychostimulant dependence, additional preclinical investigations utilizing other methodologies to examine modafinil in combination with other stimulants, such as behavioral sensitization paradigms or drug self-administration, may be of interest. © 2013.

  12. Association of Leukocytosis with Amphetamine and Cocaine Use

    Directory of Open Access Journals (Sweden)

    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.

  13. Amphetamine enantiomer excretion profile following administration of Adderall.

    Science.gov (United States)

    Cody, John T; Valtier, Sandra; Nelson, Stephen L

    2003-10-01

    Amphetamine remains a widely abused drug throughout the world. It is also used therapeutically for weight loss, narcolepsy, and attention deficit disorder with hyperactivity (ADHD). ADHD has grown dramatically recently both in terms of diagnosis and treatment. Increasingly, older individuals are diagnosed and treated for ADHD, and treatment often continues into adulthood. Of the available treatments for ADHD, Adderall is widely prescribed. Despite its widespread use, there are no published data regarding the expected amphetamine excretion profile following its use. This is problematic because, in this case, medical review officers (MRO) and forensic toxicologists are asked to assess results in terms of use pursuant to valid medical prescription without specific data on which to base a sound decision. To address this situation, a study to determine the concentration and enantiomer composition of amphetamine excretion following administration of Adderall was undertaken. Adderall (20 mg) was administered to five healthy subjects with all subsequent ad lib urine samples (total urine void) collected for seven days. Adderall is a 3:1 mixture of d- and l-enantiomers of amphetamine salts. Peak amphetamine concentrations ranged from 2645 to 5948 ng/mL. Samples containing > or = 500 ng/mL of amphetamine (the administrative cutoff for a positive result by gas chromatography-mass spectrometry) were seen up to 47:30 h post dose. The number of samples that contained amphetamine concentrations of > or = 500 ng/mL ranged among individuals from 7 to 13. As anticipated, analysis showed the d-enantiomer to be in excess of the l-enantiomer, with the proportion of l-enantiomer increasing over time. Because of the mixture of enantiomers, not all samples that contained > or = 500 ng/mL of amphetamine were positive when tested by immunoassay. The drug concentration profiles were quite variable within and between subjects because of dilution and fluctuations in pH of the samples. These

  14. Effects of amphetamine administration on neurogenesis in adult rats

    Directory of Open Access Journals (Sweden)

    Tomasz Stępień

    2017-12-01

    Full Text Available In our study expression of phospho-(Ser-10-histone H3 (pH3S10, a marker for the early stage of neurogenesis, and cellular early response genes were investigated using c-Fos protein as an example of a transcription factor in the neurogenic process in rats. Neurogenesis in the adult brain is regulated by endo- and exogenous factors, which influence the proliferation potential of progenitor cells and accelerate the dendritic development of newborn neurons. D-amphetamine, a psychoactive substance, is one of the exogenous factors able to influence the process of neurogenesis. The rats were injected with D-amphetamine at a dose of 1.5 mg/kg/body weight (b.w. under one administration scheme. Analysis of the pH3S10 and c-Fos expression levels in the group of D-amphetamine administered rats provided evidence of enhanced expression of these proteins in the regions of neurogenesis occurrence in rats. However, conclusions concerning stimulant effects of amphetamine on neurogenesis should be formulated with great caution, taking into account amphetamine dosage and the administration scheme. It should also be remembered that doses of psychoactive substances used in animal models can be lethal to humans.

  15. Methamphetamine and amphetamine derived from the metabolism of selegiline.

    Science.gov (United States)

    Romberg, R W; Needleman, S B; Snyder, J J; Greedan, A

    1995-11-01

    Routine methamphetamine testing identified a urine specimen with inconsistent screening and confirmation results. The methamphetamine RIA screening test (Diagnostic Products Corporation) indicated a borderline positive specimen, while the achiral confirmatory GC/MS result showed 4690 ng/mL of methamphetamine and 1895 ng/mL of amphetamine. Analysis of the specimen after derivatization with S(-)-N-trifluoroacetylprolyl chloride showed only the presence of 1-amphetamine and 1-methamphetamine. It was later learned that the individual providing the specimen had been taking Selegiline. Selegiline, (-) propynylmethamphetamine, is a monoamine oxidase inhibitor used for the treatment of Parkinson's disease. It is sold under the trade name Eldepryl. Its major metabolites are 1-methamphetamine, 1-amphetamine and N-desmethylselegiline. Urine specimens from other Selegiline users were obtained and analyzed. A characteristic metabolic pattern was noted, exemplified by a ratio of 1-methamphetamine to 1-amphetamine of about 2.8. This is in contrast to what is observed in the urine of individuals who ingest pure 1-methamphetamine, such as with Vicks Inhaler, where the 1-methamphetamine to 1-amphetamine ratio in the urine is usually greater than 8. Caution is advised when interpreting methamphetamine results without using a chiral identification technique.

  16. Amphetamine, past and present – a pharmacological and clinical perspective

    Science.gov (United States)

    Smith, Sharon L; Gosden, Jane; Nutt, David J

    2013-01-01

    Amphetamine was discovered over 100 years ago. Since then, it has transformed from a drug that was freely available without prescription as a panacea for a broad range of disorders into a highly restricted Controlled Drug with therapeutic applications restricted to attention deficit hyperactivity disorder (ADHD) and narcolepsy. This review describes the relationship between chemical structure and pharmacology of amphetamine and its congeners. Amphetamine’s diverse pharmacological actions translate not only into therapeutic efficacy, but also into the production of adverse events and liability for recreational abuse. Accordingly, the balance of benefit/risk is the key challenge for its clinical use. The review charts advances in pharmaceutical development from the introduction of once-daily formulations of amphetamine through to lisdexamfetamine, which is the first d-amphetamine prodrug approved for the management of ADHD in children, adolescents and adults. The unusual metabolic route for lisdexamfetamine to deliver d-amphetamine makes an important contribution to its pharmacology. How lisdexamfetamine’s distinctive pharmacokinetic/pharmacodynamic profile translates into sustained efficacy as a treatment for ADHD and its reduced potential for recreational abuse is also discussed. PMID:23539642

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Argon prevents the development of locomotor sensitization to amphetamine and amphetamine-induced changes in mu opioid receptor in the nucleus accumbens.

    Science.gov (United States)

    David, Hélène N; Dhilly, Martine; Poisnel, Géraldine; Degoulet, Mickael; Meckler, Cédric; Vallée, Nicolas; Blatteau, Jean-Éric; Risso, Jean-Jacques; Lemaire, Marc; Debruyne, Danièle; Abraini, Jacques H

    2014-01-01

    Systemic administration of γ-amino-butyric acid type A (GABA-A) and benzodiazepine receptor agonists has been reported to block the development of locomotor sensitization to amphetamine. Here, we investigated whether the non-anesthetic noble gas argon, shown to possess agonistic properties at these receptors, may block the acquisition of amphetamine-induced locomotor sensitization and mu opioid receptor activation in the nucleus accumbens. Rats were pretreated with saline solution or amphetamine (1 mg/kg) from day 1 to day 3 and then exposed, immediately after injection of amphetamine, to medicinal air or argon at 75 vol% (with the remainder being oxygen). After a 3-day period of withdrawal, rats were challenged with amphetamine on day 7. Rats pretreated with amphetamine and argon had lower locomotor activity (U = 5, P < 0.005) and mu opioid receptor activity in the nucleus accumbens (U = 0, P < 0.001) than rats pretreated with amphetamine and air. In contrast, argon had effect on locomotor and mu receptor activity neither in rats pretreated with saline and challenged with amphetamine (acute amphetamine) nor in rats pretreated and challenged with saline solution (controls). These results indicate that argon inhibits the development of both locomotor sensitization and mu opioid receptor activation induced by repeated administration of amphetamine.

  19. Amphetamines and pH-shift agents for brain imaging: Basic research and clinical results

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Winkler, C.

    1986-01-01

    This book contains 18 selections. Some of the titles are: Labelling of amphetamines with /sup 123/I: Receptors for amphetamines; New amphetamine derivatives; Potential new approaches for the development of brain imaging agents for single-photon applications; and IM SPECT with the pinhole collimator.

  20. 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. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives.

    Science.gov (United States)

    Kraemer, Thomas; Maurer, Hans H

    2002-04-01

    This paper reviews the toxicokinetics of amphetamines. The designer drugs MDA (methylenedioxy-amphetamine, R,S-1-(3;,4;-methylenedioxyphenyl)2-propanamine), MDMA (R,S-methylenedioxymethamphetamine), and MDE (R,S-methylenedioxyethylamphetamine), as well as BDB (benzodioxolylbutanamine; R,S-1-(1;,3;-benzodioxol-5;-yl)-2-butanamine or R,S-1-(3;,4;-methylenedioxyphenyl)-2-butanamine) and MBDB (R,S-N-methyl-benzodioxolylbutanamine), were taken into consideration, as were the following N-alkylated amphetamine derivatives: amphetaminil, benzphetamine, clobenzorex, dimethylamphetamine, ethylamphetamine, famprofazone, fencamine, fenethylline, fenproporex, furfenorex, mefenorex, mesocarb, methamphetamine, prenylamine, and selegiline. English-language publications from 1995 to 2000 were reviewed. Papers describing identification of metabolites or cytochrome P450 isoenzyme-dependent metabolism and papers containing pharmacokinetic/toxicokinetic data were considered and summarized. The implications of toxicokinetics for toxicologic assessment or for interpretation in forensic cases are discussed.

  2. 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. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Brain SPECT with 123I-isopropyl amphetamine in epilepsy

    International Nuclear Information System (INIS)

    Biersack, H.J.; Reske, S.N.; Rasche, A.; Reichmann, K.; Winkler, C.

    1983-01-01

    Ten patients were studied with N-isopropyl I-123 p-iodoamphetamine. Single photon emission computed tomography (SPECT) was carried out by hand of a rotating gamma camera system (Gammatome T9000/CGR, high resolution collimator). During 1 rotation (360 0 ) 64 frames (4k matrix) were acquired within 20 min 1 hour after injection of 6.5 mCi I-123 labeled amphetamine. The content of I-124 was less than 2%. After reconstruction of transverse slices coronar and sagittal reconstructions were rapidly performed using an array processor. Nine patients suffered from epilepsy and one from severe migraine. Excellent differentiation between gray and white matter of the cerebral cortex and the basal ganglia was evident in all of the cases. In 2 out of 3 patients with epilepsy and negative CT results SPECT revealed circumscribed areas with increased amphetamine uptake in accordance with the EEG findings. In 4 out of 6 cases with positive CT findings SPECT lesions with diminished amphetamine uptake could be established. One patient with severe migraine showed focal increased amphetamine uptake in accordance with the respective clinical results. (orig.)

  4. Cannabis and Amphetamine Use Among Adolescents in Five Asian Countries

    Directory of Open Access Journals (Sweden)

    Karl Peltzer

    2017-12-01

    Conclusions: Our preliminary results show the importance of personal attributes such as mental distress and environmental stressors on lifetime cannabis and lifetime amphetamine use. Future prospective studies are needed to identify causal relationships among personal attributes, parental attributes, environmental stressors, and illicit substance use.

  5. 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.

  6. A kinetic account for amphetamine-induced monoamine release.

    Science.gov (United States)

    Hasenhuetl, Peter S; Bhat, Shreyas; Mayer, Felix P; Sitte, Harald H; Freissmuth, Michael; Sandtner, Walter

    2018-02-09

    The plasmalemmal monoamine transporters for dopamine, norepinephrine, and serotonin (SERT) are targets for amphetamines. In vivo, amphetamines elicit most, if not all, of their actions by triggering monoamine efflux. This is thought to be accomplished by an amphetamine-induced switch from the forward-transport to the substrate-exchange mode. The mechanism underlying this switch has remained elusive; available kinetic models posit that substrates and cosubstrate Na + ions bind either in a random or in a sequential order. Neither can account for all reported experimental observations. We used electrophysiological recordings to interrogate crucial conformational transitions associated with the binding of five different substrates (serotonin, para -chloroamphetamine, and the high-affinity naphthyl-propan-amines PAL-287, PAL-1045, and PAL-1046) to human SERT expressed in HEK293 cells; specifically, we determined the relaxation kinetics of SERT from a substrate-loaded to a substrate-free state at various intracellular and extracellular Na + concentrations. These rates and their dependence on intracellular and extracellular Na + concentrations differed considerably between substrates. We also examined the effect of K + on substrate affinity and found that K + enhanced substrate dissociation. A kinetic model was developed, which allowed for random, but cooperative, binding of substrate and Na + (or K + ). The synthetic data generated by this model recapitulated the experimental observations. More importantly, the cooperative binding model accounted for the releasing action of amphetamines without any digression from alternating access. To the best of our knowledge, this model is the first to provide a mechanistic framework for amphetamine-induced monoamine release and to account for the findings that some substrates are less efficacious than others in promoting the substrate-exchange mode. © 2018 Hasenhuetl et al.

  7. 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.

  8. Amphetamine and antidepressant drug effects on GABA- and NMDA-related seizures.

    Science.gov (United States)

    Borowski, T B; Kirkby, R D; Kokkinidis, L

    1993-01-01

    Research has shown a synergistic relationship between amphetamine sensitization and limbic system kindling. To explore the role of GABA and NMDA receptor activity in modulating the positive effects of amphetamine on epileptogenesis, alterations in GABA- and NMDA-related convulsions were examined after acute and chronic amphetamine administration. A single injection of d-amphetamine (7.5 mg/kg) significantly decreased latencies to generalized motor seizures induced 12 h later by the noncompetitive GABAA receptor antagonist picrotoxin (10 mg/kg). The increased sensitivity to clonus was specific to acute amphetamine treatment and was not evident following withdrawal from chronic drug exposure. Seizures induced by NMDLA (1,000 mg/kg), on the other hand, were not modified by acute amphetamine injection; however, the latency to clonus was reduced substantially after NMDLA injection to mice chronically preexposed to amphetamine. The short- and long-term amphetamine effects on GABA- and NMDA-associated convulsive activity were not paralleled by similar drug treatment schedules involving acute (20 mg/kg) and chronic administration of desipramine, zimelidine, and buproprion. These results suggest that amphetamine may be acting on inhibitory and excitatory amino acid systems independently of its monoaminergic properties. The implications of these findings were discussed in relation to amphetamine sensitization of mesolimbic functioning.

  9. Adderall produces increased striatal dopamine release and a prolonged time course compared to amphetamine isomers.

    Science.gov (United States)

    Joyce, B Matthew; Glaser, Paul E A; Gerhardt, Greg A

    2007-04-01

    Adderall is currently used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) and is composed of a novel mixture of approximately 24% L-amphetamine and 76% D-amphetamine salts. There are, however, no investigations of the pharmacological effects of this combination in vivo. The technique of high-speed chronoamperometry using Nafion-coated single carbon-fiber microelectrodes was used to study amphetamine-evoked dopamine (DA) release produced by Adderall, D-amphetamine, or D,L-amphetamine in the striatum of anesthetized male Fischer 344 (F344) rats. The amphetamine solutions were locally applied from micropipettes by pressure ejection. Local applications of Adderall resulted in significantly greater DA release signal amplitudes with prolonged time course of dopamine release and re-uptake as compared to D-amphetamine and D,L-amphetamine. These data support the hypothesis that the combination of amphetamine enantiomers and salts in Adderall has effects on DA release, which result in increased and prolonged DA release, compared to D- and D,L-amphetamine.

  10. Efficacy of psychostimulant drugs for amphetamine abuse or dependence.

    Science.gov (United States)

    Pérez-Mañá, Clara; Castells, Xavier; Torrens, Marta; Capellà, Dolors; Farre, Magi

    2013-09-02

    Amphetamine dependence is a public health problem with medical, psychiatric, cognitive, legal and socioeconomic consequences. To date, no pharmacological treatment has been approved for this disorder, and psychotherapy remains the mainstay of treatment. In recent years, psychostimulants have been investigated as a possible replacement therapy. To evaluate the efficacy and safety of psychostimulant medications for amphetamine abuse or dependence. The influences of type of drug, type of dependence, comorbid disorders, clinical trial risk of bias and publication of data were also studied. Relevant trials were searched in the following sources: PubMed (January 1966 to 6 June 2012), EMBASE (January 1988 to 6 June 2012), CENTRAL (The Cochrane Library, Issue 5 of 12, May 2012), PsycINFO (January 1985 to 6 June 2012) and the Specialised Register of the Cochrane Drug and Alcohol Group (June 2012). We also searched the reference lists of retrieved trials, the list of studies citing the included trials and the main electronic registers of ongoing trials (ClinicalTrials.gov, International Clinical Trials Registry Platform and EU Clinical Trials Register). Finally, we contacted investigators to request information about unpublished trials. Searches included non-English language literature. All randomised, placebo-controlled, parallel-group clinical trials investigating the efficacy or safety of psychostimulants for amphetamine dependence or abuse conducted in an outpatient setting. We used standard methodological procedures expected by The Cochrane Collaboration. Eleven studies were included in the review (791 participants). Studied psychostimulants included dexamphetamine, bupropion, methylphenidate and modafinil. No significant differences were found between psychostimulants and placebo for any of the studied efficacy outcomes. Overall retention in studies was low (50.4%). Psychostimulants did not reduce amphetamine use (mean difference (MD) -0.26, 95% confidence interval (CI

  11. Amphetamine-type medicines: a review of pharmacokinetics, pharmacodynamics, and toxicological aspects.

    Science.gov (United States)

    Mariotti, Kristianee C; Rossato, Luciana G; Fröehlich, Pedro E; Limberger, Renata P

    2013-11-01

    Amphetamine-like drugs are sympathomimetic agents with marked central and peripheral stimulant properties. Despite the street illegal drugs such as amphetamine and ecstasy, some amphetamine-like compounds are also legally marketed under medical prescription in the treatment of attention deficit-hyperactivity disorder (methylphenidate) and obesity/overweight (fenproporex and diethylpropione). However, similar with what happens with their illicit analogues, therapeutic amphetamine-like drugs also share important toxicological risks. Although methylphenidate is considered the first choice in the treatment of attention deficit-hyperactivity disorder, its high popularity among teenagers and children is raising concern in the medical community. Regarding weight-loss purposes, the use of amphetamine-like compounds are very controversial, though. Thus, the present review will address pharmacokinetic, pharmacodynamic, and toxicological aspects of amphetamine-like compounds used with therapeutic aims.

  12. Heterocyclic amphetamine derivatives and caffeine on sleep in man

    OpenAIRE

    Nicholson, A. N.; Stone, Barbara M.

    1980-01-01

    1 Effects of the heterocyclic amphetamine derivatives, pemoline (20 and 40 mg), prolintane hydrochloride (5 and 10 mg), methylphenidate hydrochloride (10 and 20 mg) and fencamfamine hydrochloride (10 and 20 mg), and of caffeine anhydrous (100, 200 and 300 mg) on sleep, were compared with placebo in six young adults (20-31 years) using electroencephalography for sleep measures and analogue scales for subjective assessments of well-being and sleep quality. The study was double-blind.

  13. Emotional traits predict individual differences in amphetamine-induced positive mood in healthy volunteers.

    Science.gov (United States)

    Kirkpatrick, Matthew G; Goldenson, Nicholas I; Kapadia, Nahel; Kahler, Christopher W; de Wit, Harriet; Swift, Robert M; McGeary, John E; Sussman, Steve; Leventhal, Adam M

    2016-01-01

    Previous research on emotional correlates of individual differences in subjective responses to D-amphetamine has focused on relatively broad personality traits. Yet, emotional functioning is best characterized by several narrow subcomponents, each of which may contribute uniquely to amphetamine response. Here, we examine several specific subdomains of emotional functioning in relation to acute amphetamine response. At a baseline session, healthy stimulant-naive volunteers (N = 97) completed measures of several subdomains of baseline trait emotional functioning and then completed two counterbalanced experimental sessions during which they received a single oral dose of 20 mg D-amphetamine or placebo. Acute subjective drug response measures were completed at repeated intervals before and after drug administration. Data from subjective measures that were significantly modulated by amphetamine were reduced using principal component analysis (amphetamine or placebo) into three higher-order factors of "positive mood," "arousal," and "drug high." Amphetamine did not significantly alter any "negative" subjective states. Separate multiple regression analyses were conducted regressing these three drug factors on baseline trait emotional functioning scales. The combined set of trait emotional functioning indicators accounted for approximately 22 % of the variance in acute amphetamine-induced positive mood changes. Greater anticipatory pleasure and greater anxious distress each uniquely predicted greater amphetamine-induced positive mood. Trait emotional functioning did not significantly predict amphetamine-induced changes in arousal or drug high. Emotional traits appear to moderate drug-induced positive mood but not other dimensions of amphetamine effects. Different facets of emotional functioning may differentially modulate amphetamine's subjective effect profile.

  14. Pharmacokinetics and Pharmacodynamics of Lisdexamfetamine Compared with D-Amphetamine in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Patrick C. Dolder

    2017-09-01

    Full Text Available Rationale: Lisdexamfetamine is a prodrug of D-amphetamine used for the treatment of attention-deficit/hyperactivity disorder (ADHD. Lisdexamfetamine is thought to have a prolonged pharmacokinetic profile compared with oral D-amphetamine, possibly associated with lower drug liking and a lower risk of oral misuse. However, differences in the pharmacokinetics and pharmacodynamics of lisdexamfetamine and D-amphetamine have not been directly compared.Methods: Equimolar doses of D-amphetamine (40 mg and lisdexamfetamine (100 mg, and placebo were administered in 24 healthy subjects in a randomized, double-blind, placebo-controlled, cross-over study. Plasma concentrations of amphetamine, subjective effects, and vital signs were repeatedly assessed. The pharmacokinetic parameters were determined using compartmental modeling.Results: The increase in plasma concentrations of amphetamine had a 0.6 ± 0.6 h (mean ± SD longer lag time and reached peak levels 1.1 ± 1.5 h later after lisdexamfetamine administration compared with D-amphetamine administration, but no differences in maximal concentrations or total exposure (AUC were found between the two treatments. Consistent with the pharmacokinetics, the subjective and cardiovascular stimulant effects of lisdexamfetamine also occurred later compared with D-amphetamine. However, no differences in peak ratings of potentially abuse-related subjective drug effects (e.g., drug liking, drug high, stimulation, happy, well-being, and self-confidence were observed after lisdexamfetamine administration compared with D-amphetamine administration. Lisdexamfetamine and D-amphetamine also produced similar peak increases in mean arterial blood pressure, heart rate, body temperature, pupil size, and adverse effects.Conclusion: The pharmacokinetics and pharmacodynamics of lisdexamfetamine are similar to D-amphetamine administered 1h later. Lisdexamfetamine is likely associated with a similar risk of oral abuse as D-amphetamine

  15. 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.

  16. 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.

  17. Amphetamine activates Rho GTPase signaling to mediate dopamine transporter internalization and acute behavioral effects of amphetamine

    Science.gov (United States)

    Wheeler, David S.; Underhill, Suzanne M.; Stolz, Donna B.; Murdoch, Geoffrey H.; Thiels, Edda; Romero, Guillermo; Amara, Susan G.

    2015-01-01

    Acute amphetamine (AMPH) exposure elevates extracellular dopamine through a variety of mechanisms that include inhibition of dopamine reuptake, depletion of vesicular stores, and facilitation of dopamine efflux across the plasma membrane. Recent work has shown that the DAT substrate AMPH, unlike cocaine and other nontransported blockers, can also stimulate endocytosis of the plasma membrane dopamine transporter (DAT). Here, we show that when AMPH enters the cytoplasm it rapidly stimulates DAT internalization through a dynamin-dependent, clathrin-independent process. This effect, which can be observed in transfected cells, cultured dopamine neurons, and midbrain slices, is mediated by activation of the small GTPase RhoA. Inhibition of RhoA activity with C3 exotoxin or a dominant-negative RhoA blocks AMPH-induced DAT internalization. These actions depend on AMPH entry into the cell and are blocked by the DAT inhibitor cocaine. AMPH also stimulates cAMP accumulation and PKA-dependent inactivation of RhoA, thus providing a mechanism whereby PKA- and RhoA-dependent signaling pathways can interact to regulate the timing and robustness of AMPH’s effects on DAT internalization. Consistent with this model, the activation of D1/D5 receptors that couple to PKA in dopamine neurons antagonizes RhoA activation, DAT internalization, and hyperlocomotion observed in mice after AMPH treatment. These observations support the existence of an unanticipated intracellular target that mediates the effects of AMPH on RhoA and cAMP signaling and suggest new pathways to target to disrupt AMPH action. PMID:26553986

  18. Predictors of young adults' amphetamine use and disorders: a prospective study.

    Science.gov (United States)

    Hayatbakhsh, Mohammad R; Najman, Jake M; Bor, William; Williams, Gail M

    2009-05-01

    Understanding the risk factors that predict amphetamine use and development of amphetamine abuse or dependence (disorder) may help guide preventive interventions. This study aimed to investigate the correlates and predictors of young adults' amphetamine use and use disorders. Prospective cohort, population-based study which started in Brisbane, South East Queensland (Australia) in 1981. The study participants were a cohort of 2042 young adults, followed up from birth to young adulthood. At the 21-year follow-up, amphetamine use was assessed via a self-report questionnaire, and amphetamine use disorder (AUD) was assessed using the Composite International Diagnostic Interview (CIDI-Auto). Potential predictors (15 risk factors) were assessed between baseline (antenatal visit) and the 21-year follow-up. These included participant's gender, mother's age and education, maternal marital status and quality of marital relationship, maternal tobacco and alcohol consumption, mother-child communication, child mental health and problem behaviours, child smoking and alcohol consumption and child school performance. Young adult amphetamine users were more likely to have concurrent symptoms of mental illness and problem behaviours and to use or abuse cigarettes, cannabis, or other illicit drugs. In multivariate analyses, young adults' amphetamine use and disorder were disproportionately more common among males and those who have prospectively reported aggression/delinquency or smoking at 14 years, or who have experienced childhood sexual abuse. Our findings suggest that problem behaviours, smoking and childhood sexual abuse are predictors of initiation to use of amphetamines and development of amphetamine abuse and dependence.

  19. 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

  20. The relationship of quality and price of the psychostimulants cocaine and amphetamine with health care outcomes

    NARCIS (Netherlands)

    Brunt, Tibor M.; van Laar, Margriet; Niesink, Raymond J. M.; van den Brink, Wim

    2010-01-01

    A major component of the illicit drug market can be subcategorized as the psychostimulant drug market, with cocaine and amphetamine as popular constituents. In The Netherlands, an increase in both health care outcomes addiction treatment and hospital admissions was noted for both amphetamine and

  1. 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...

  2. 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 inhalers regarded as prescription drugs. (a) Recurring reports of abuse and misuse of methamphetamine (also...

  3. Amphetamine Elicits Opposing Actions on Readily Releasable and Reserve Pools for Dopamine

    Science.gov (United States)

    Covey, Dan P.; Juliano, Steven A.; Garris, Paul A.

    2013-01-01

    Amphetamine, a highly addictive drug with therapeutic efficacy, exerts paradoxical effects on the fundamental communication modes employed by dopamine neurons in modulating behavior. While amphetamine elevates tonic dopamine signaling by depleting vesicular stores and driving non-exocytotic release through reverse transport, this psychostimulant also activates phasic dopamine signaling by up-regulating vesicular dopamine release. We hypothesized that these seemingly incongruent effects arise from amphetamine depleting the reserve pool and enhancing the readily releasable pool. This novel hypothesis was tested using in vivo voltammetry and stimulus trains of varying duration to access different vesicular stores. We show that amphetamine actions are stimulus dependent in the dorsal striatum. Specifically, amphetamine up-regulated vesicular dopamine release elicited by a short-duration train, which interrogates the readily releasable pool, but depleted release elicited by a long-duration train, which interrogates the reserve pool. These opposing actions of vesicular dopamine release were associated with concurrent increases in tonic and phasic dopamine responses. A link between vesicular depletion and tonic signaling was supported by results obtained for amphetamine in the ventral striatum and cocaine in both striatal sub-regions, which demonstrated augmented vesicular release and phasic signals only. We submit that amphetamine differentially targeting dopamine stores reconciles the paradoxical activation of tonic and phasic dopamine signaling. Overall, these results further highlight the unique and region-distinct cellular mechanisms of amphetamine and may have important implications for its addictive and therapeutic properties. PMID:23671560

  4. HIV Risk Behavior among Amphetamine Injectors at U.S. Syringe Exchange Programs

    Science.gov (United States)

    Braine, Naomi; Des Jarlais, Don C.; Goldblatt, Cullen; Zadoretzky, Cathy; Turner, Charles

    2005-01-01

    The goal of this study was to compare HIV risk behaviors of amphetamine and non-amphetamine injectors at syringe exchange programs (SEP) in the United States and to identify factors associated with injection risk. This analysis is based on data from a random cross-section of participants at 13 SEPs in different parts of the country. All interviews…

  5. 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 a...

  6. Dextro-amphetamine increases phosphoinositol cycle activity in volunteers: an MRS study.

    Science.gov (United States)

    Silverstone, Peter H; O'Donnell, Tina; Ulrich, Michele; Asghar, Sheila; Hanstock, Christopher C

    2002-12-01

    To help determine the effects of dextro-amphetamine on the phosphoinositol cycle (PI-cycle) in humans, (1)H and (31)P magnetic resonance spectroscopy (MRS) was utilized in 17 healthy volunteers. This was an open-label study carried out before and after administration of 20 mg oral dextro-amphetamine. Subjects also rated the subjective effects of dextro-amphetamine administration using visual analog scales (VAS). Following dextro-amphetamine administration there was a significant increase in the concentrations of both myo-inositol and phosphomonoesters. These findings are in keeping with suggestions that dextro-amphetamine administration increases the activity of the phosphoinositol cycle, probably via an indirect release of dopamine and noradrenaline. These results are the first time that this has been confirmed in humans. Copyright 2002 John Wiley & Sons, Ltd.

  7. Amphetamine-like stimulant cessation in an abusing patient treated with bupropion.

    Science.gov (United States)

    Tardieu, S; Poirier, Y; Micallef, J; Blin, O

    2004-01-01

    Bupropion sustained release is considered to be a weak inhibitor of dopamine and serotonin reuptake. We report the case of an amphetamine-abusing patient who self-administered bupropion. Since 30 years, a 52-year-old women used amphetamine derivates. She explained her need for amphetamine use in order to perform daily activities. Recently, she decided to experiment with bupropion. She abruptly stopped taking clobenzorex and simultaneously started taking bupropion (150 mg/day). The seventh day she reported a concomitant intake of clobenzorex; this induced adverse effects. Whilst taking bupropion, she described experiencing an euthymic state without any compulsion to take amphetamine drugs and was able to perform daily activities. After stopping it, no symptoms of withdrawal were reported by the patient. This observation supports an another report suggesting that bupropion may be of help in weaning from amphetamine users and should be confirmed by clinical trials.

  8. 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.

  9. Nicotine Modifies Corticostriatal Plasticity and Amphetamine Rewarding Behaviors in Mice123

    Science.gov (United States)

    Storey, Granville P.; Heimbigner, Lauren; Walwyn, Wendy M.; Bamford, Nigel S.

    2016-01-01

    Abstract Corticostriatal signaling participates in sensitized responses to drugs of abuse, where short-term increases in dopamine availability provoke persistent, yet reversible, changes in glutamate release. Prior studies in mice show that amphetamine withdrawal promotes a chronic presynaptic depression in glutamate release, whereas an amphetamine challenge reverses this depression by potentiating corticostriatal activity in direct pathway medium spiny neurons. This synaptic plasticity promotes corticostriatal activity and locomotor sensitization through upstream changes in the activity of tonically active cholinergic interneurons (ChIs). We used a model of operant drug-taking behaviors, in which mice self-administered amphetamine through an in-dwelling catheter. Mice acquired amphetamine self-administration under fixed and increasing schedules of reinforcement. Following a period of abstinence, we determined whether nicotinic acetylcholine receptors modified drug-seeking behavior and associated alterations in ChI firing and corticostriatal activity. Mice responding to conditioned reinforcement showed reduced ChI and corticostriatal activity ex vivo, which paradoxically increased following an amphetamine challenge. Nicotine, in a concentration that increases Ca2+ influx and desensitizes α4β2*-type nicotinic receptors, reduced amphetamine-seeking behaviors following abstinence and amphetamine-induced locomotor sensitization. Nicotine blocked the depression of ChI firing and corticostriatal activity and the potentiating response to an amphetamine challenge. Together, these results demonstrate that nicotine reduces reward-associated behaviors following repeated amphetamine and modifies the changes in ChIs firing and corticostriatal activity. By returning glutamatergic activity in amphetamine self-administering mice to a more stable and normalized state, nicotine limits the depression of striatal activity in withdrawal and the increase in activity following

  10. Discordant reporting of nonmedical amphetamine use among Adderall-using high school seniors in the US.

    Science.gov (United States)

    Palamar, Joseph J; Le, Austin

    2017-12-01

    Amphetamine is the most prevalent prescription stimulant in the United States, both medically and nonmedically. Reliable data on nonmedical use is needed to continue to inform prevention. To determine whether adolescents accurately self-report nonmedical amphetamine use, we compared self-reports of nonmedical amphetamine use and nonmedical Adderall use in a national sample. We examined self-reported nonmedical Adderall and amphetamine use in a nationally representative sample of 24,740 high school seniors in the Monitoring the Future study (2010-2015). We examined prevalence and correlates of discordant responses among past-year Adderall users, defined as reporting past-year nonmedical Adderall use, but not reporting past-year nonmedical amphetamine use. While 6.9% reported nonmedical Adderall use and 7.9% reported nonmedical amphetamine use, over a quarter (28.7%) of Adderall users reported no amphetamine use. Those at highest risk for Adderall use tended to be at lower odds of providing a discordant response. Older students (aged ≥18), black students, and those with parents of lower educational attainment were more likely to report no amphetamine use, despite reporting Adderall use. Lifetime use of various drugs was associated with decreased odds of providing a discordant response; however, only nonmedical opioid use was associated with significant decreased odds in multivariable models. Disapproval towards amphetamine use increased odds of providing a discordant response, while higher exposure to users decreased odds of providing a discordant response. Prevalence of nonmedical amphetamine use may be underreported on some surveys, particularly among specific subpopulations. Future surveys must ensure accurate and consistent responses. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Comparative symptomatological and evoked potential studies with d-amphetamine, thioridazine, and placebo in hyperkinetic children.

    Science.gov (United States)

    Saletu, B; Saletu, M; Simeon, J; Viamontes, G; Itil, T M

    1975-06-01

    In a double-blind study, 62 hyperkinetic children were randomly assigned to 8 weeks of treatment with either placebo, thioridazine, or d-amphetamine. The overall clinical symptomatology improved with all three substances, although d-amphetamine was significantly superior to placebo and thioridazine. Out of eight symptom clusters rated by the parents, two improved significantly with placebo, one with thioridazine, and six with d-amphetamine. The d-amphetamine was superior to placebo in reducing muscular tension and superior to thioridazine in decreasing hyperactive-impulsive behavior, psychosomatic problems, and muscular tension. Out of four teachers' symptom clusters, inattentive-passive behavior was significantly improved by thioridazine (which was also superior to placebo), while hyperactivity was reduced by d-amphetamine. Quantitative evaluation of visual evoked potentials (VEPs) revealed an increase in latencies and decrease in amplitudes during thioridazine treatment. Paradoxically, d-amphetamine also increased latencies, while tending to augment amplitudes. Regression and correlation analysis of clinical symptomatology with VEP variables showed that the shorter the pretreatment latencies and the higher the amplitudes, the more disturbed was the child. Short latencies and small amplitudes in the pretreatment period were predictors of good therapeutic outcome with subsequent thioridazine treatment, while short latencies and high amplitudes were indicative of such with d-amphetamine treatment. During therapy, the greater the drug-induced augmentation of latencies, the greater the clinical improvement. Finally, VEP differences between therapy-responsive and -resistant patients were explored and discussed.

  12. Metabolism and disposition of N-(2-cyanoethyl)amphetamine (fenproporex) and amphetamine: study in the rat brain.

    Science.gov (United States)

    Coutts, R T; Nazarali, A J; Baker, G B; Pasutto, F M

    1986-06-01

    N-(2-Cyanoethyl)amphetamine (fenproporex, CE-AM) is a clinically used anorexiant claimed to be devoid of the stimulant properties associated with amphetamine (AM). This claim was inconsistent with preliminary studies conducted in our laboratories which indicated that CE-AM is metabolically dealkylated to AM to a considerable extent in the rat. Concentration-time profiles of CE-AM and its metabolites AM and 4-hydroxyamphetamine (4-OH-AM) in the rat brain were constructed after administration of CE-AM. Analyses of CE-AM, AM, and 4-OH-AM were performed by gas chromatography with electron-capture detection using pentafluorobenzoyl chloride (under aqueous conditions) as the derivatizing reagent. The half-life (t1/2) and the maximum concentration (Cmax) of AM after administration of CE-AM were calculated to be 2.04 and 0.56 times the respective t1/2 and Cmax obtained after an equimolar dose of AM. Significant differences in the profiles of 4-OH-AM were also observed. The Cmax of 4-OH-AM in rat brain after administration of CE-AM was nearly 4 times higher and the tmax (time at which concentration is maximum) 4 times lower than the respective Cmax and tmax values of 4-OH-AM observed after an equimolar dose of AM.

  13. Differentiation of clobenzorex use from amphetamine abuse using the metabolite 4-hydroxyclobenzorex.

    Science.gov (United States)

    Valtier, S; Cody, J T

    2000-10-01

    Clobenzorex (Asenlix) is an anorectic drug metabolized by the body to amphetamine, thus causing difficulty in the interpretation of amphetamine-positive drug tests. Previous studies have shown the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h postdose using a detection limit of 1 ng/mL. Despite this fact, several amphetamine-positive samples (> or = 500 ng/mL) contained no detectable clobenzorex. Thus, the absence of clobenzorex in the urine does not exclude the possibility of its use. To more definitively assess the possibility of clobenzorex use, evaluation of another metabolite was considered. One study reported the presence of unidentified hydroxy metabolites of clobenzorex for as long as amphetamine was detected in some subjects. To assess the viability of using a hydroxy metabolite to confirm the use of clobenzorex in samples containing amphetamine, 4-hydroxyclobenzorex was synthesized for this study. This metabolite proved to be easily detected and was typically found at levels higher than amphetamine in amphetamine-positive urines, long after clobenzorex itself was no longer detected. Samples obtained from a controlled single-dose study involving the administration of clobenzorex (30 mg) were analyzed for the presence of the 4-hydroxy metabolite. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and analysis with gas chromatography-mass spectrometry by monitoring ions at m/z 125, 330, and 364. 4-Hydroxyclobenzorex and its 3-Cl regioisomer were used in the identification and quantitation of the metabolite. Peak concentrations of 4-hydroxyclobenzorex were found at approximately 1:30-5:00 h postdose and ranged from approximately 5705 to 88,410 ng/mL. Most importantly, however, all samples that contained amphetamine at > or = 500 ng/mL also contained detectable amounts of this hydroxy metabolite (LOD 10 ng/mL), making it a valuable tool in differentiating use

  14. Amphetamine poisoning in a dog: case report, literature review and veterinary medical perspectives.

    Science.gov (United States)

    Diniz, Pedro Paulo V P; Sousa, Marlos G; Gerardi, Daniel G; Tinucci-Costa, Mirela

    2003-12-01

    Amphetamine abuse in human beings has increased, resulting in many reports of toxicity and death. In the US over 4 million people have abused amphetamines at least once, thus small animals are exposed to increased accidental poisoning risk. This report describes an acute amphetamine poisoning in a dog due to ingestion of 15 mg/kg fenproporex, leading to typical signs of catecholamines release and effects in different organ systems. Similar clinical and laboratory findings observed in human beings are reviewed and physiopathogenic mechanisms discussed, as well as the therapeutic approaches available in veterinary medicine.

  15. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Smith, Douglas A; Kisor, David F; Poklis, Justin L

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  16. Orthostatic hypotension due to suppression of vasomotor outflow after amphetamine intoxication

    NARCIS (Netherlands)

    Smit, A. A.; Wieling, W.; Voogel, A. J.; Koster, R. W.; van Zwieten, P. A.

    1996-01-01

    Ten hours after ingestion of amphetamines, a previously healthy 17-year-old female adolescent experienced dizziness on standing. Examination revealed pronounced drowsiness and severe orthostatic hypotension. Assessment of arterial baroreflex function suggested that suppressed sympathetic vasomotor

  17. 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

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

    OpenAIRE

    Acevedo Urrego, Marcela; Arango Orozco, Lisa; Blandón Montoya, Liliana; Buelvas Soto, Liz; Carmona Velasquez, Daybeth Vanesa; Castaño Castrillón, Jose Jaime; Castro Rocha, Betsy Carolina; Serna, Juan Camilo; Trujillo Sandoval, Karol Susana; Arango, César

    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...

  19. The Relative Reinforcing Strength of Methamphetamine and d-Amphetamine in Monkeys Self-Administering Cocaine

    OpenAIRE

    Lile, Joshua A.; Charnigo, Richard J.; Nader, Michael A.

    2013-01-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of d-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially-increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of d-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A ran...

  20. Combination of modafinil and d-Amphetamine for the treatment of cocaine dependence: A preliminary investigation

    Directory of Open Access Journals (Sweden)

    Joy M Schmitz

    2012-08-01

    Full Text Available Background: Two stimulant medications, modafinil and d-amphetamine, when tested individually, have shown safety and efficacy for treatment of cocaine addiction. We hypothesized that the combination of modafinil and d-amphetamine, at low doses, would show equivalent or greater benefit in reducing cocaine use compared to higher doses of each individual medication or placebo. Methods: Sixteen week, randomized, parallel-group design with four treatment arms comparing placebo to modafinil 400 mg; d-amphetamine 60 mg; modafinil 200 mg plus d-amphetamine 30 mg. Primary outcome variables, retention and cocaine use, were analyzed on the sample of 73 participants who received the first dose of the study medication. Results: Retention rates did not differ between groups and were generally low, with 40% remaining in treatment at week 12 and 20% at week 16. Participants receiving the combination of modafinil and d-amphetamine showed a trend of increased cocaine use over time with a corresponding low Bayesian probability of benefit (33%. Relatively better cocaine outcomes were observed in the placebo and d-amphetamine only groups. The study medications were generally well-tolerated with few adverse effects, yet rates of adherence were suboptimal (≤ 80%. Conclusion: Data from this preliminary investigation fail to provide evidential support for conducting a larger study of this dual-agonist medication combination for treatment of cocaine dependence.

  1. Metabolic profile of amphetamine and methamphetamine following administration of the drug famprofazone.

    Science.gov (United States)

    Greenhill, Brandy; Valtier, Sandra; Cody, John T

    2003-10-01

    There are a several drugs that lead to the production of methamphetamine and/or amphetamine in the body which are subsequently excreted in the urine. These drugs raise obvious concerns when interpreting positive amphetamine drug testing results. Famprofazone is an analgesic found in a multi-ingredient medication (Gewodin) used for pain relief. Two Gewodin tablets (50 mg of famprofazone) were administered orally to healthy volunteers with no history of amphetamine, methamphetamine, or famprofazone use. Following administration, urine samples were collected ad lib for up to six days, and pH, specific gravity, and creatinine values were determined. In order to determine the quantitative excretion profile of amphetamine and methamphetamine, samples were extracted using liquid-liquid extraction, derivatized with heptafluorobutyric anhydride, and analyzed by gas chromatography-mass spectrometry (GC-MS). The ions monitored were 91, 118, 240 for amphetamine and 254, 210, 118 for methamphetamine. Amphetamine-d(6) and methamphetamine-d(11) were used as internal standards. Peak concentrations for amphetamine ranged from 148 to 2271 ng/mL and for methamphetamine 615 to 7361 ng/mL. Concentrations of both compounds peaked between 3 and 7 h post-dose. Amphetamine and methamphetamine could be detected (limit of detection = 5 ng/mL) at 121 and 143 h post-dose, respectively. Using a cutoff of 500 ng/mL, all subjects had individual urine samples that tested positive. One subject had 14 samples above the cutoff with the last positive being detected over 48 h post-dose. The profile of methamphetamine and amphetamine enantiomers was also determined using liquid-liquid extraction, derivatization with N-trifluoroacetyl-l-prolyl chloride and analysis by GC-MS. Data showed the famprofazone metabolites amphetamine and methamphetamine to be both d- and l-enantiomers. The proportion of l-methamphetamine exceeded that of its d-enantiomer from the first sample collected. Initially, the

  2. Development and evaluation of a radioimmunoassay for the detection of amphetamine and related compounds in biological fluids

    International Nuclear Information System (INIS)

    Mason, P.A.; Bal, T.S.; Law, B.; Moffat, A.C.

    1983-01-01

    A radioimmunoassay has been developed for the detection of amphetamine and its analogues in blood and urine without any pretreatment of the samples. It is based on a commercially available antiserum and a [ 125 I] iodinated derivative of amphetamine. The assay can detect low levels of amphetamine (less than 10 ng ml - 1 ) in very small samples (50 μl) of blood and urine. It is cheap (3 pence per test), rapid, simple to perform and is specific for compounds closely related to amphetamine. A high, positive correlation was obtained (r = 0.93) when results of the analyses of urine samples from volunteers who had ingested amphetamine were compared with those produced by gas chromatography - mass spectrometry. The assay has proved very useful for the detection of amphetamine and closely related compounds in biological fluids. (author)

  3. Amphetamine use and its associated factors in body builders: a study from Tehran, Iran.

    Science.gov (United States)

    Angoorani, Hooman; Narenjiha, Hooman; Tayyebi, Behnoosh; Ghassabian, Akhgar; Ahmadi, Gelareh; Assari, Shervin

    2012-05-09

    Epidemiological studies on all types of illicit drug use among athletes are essential for both the sport community and drug control achievements. Here, we investigated the prevalence and associated factors of amphetamine use in body builders in Tehran, Iran, 2007. This study is a secondary analysis of a substance use survey done in 103 randomly selected gymnasia in Tehran (capital city of Iran). The survey was conducted from November 2007 to January 2008 and included 843 randomly selected bodybuilders (aged 40 years or less). By interviews via questionnaires the following data were obtained: age, job, marital status, education level, housing status, average monthly family income, number of family members, gymnasium area (m(2)), number of trainers, number of gymnasium members, initiation time (months), weekly duration of the sporting activity (h), monthly cost of the sporting activity, purpose of participating in sporting activity, and history of anabolic steroid and amphetamine use. One hundred twenty (13.3%) body builders reported a history of amphetamine use. According to the results of regression analysis, being married (risk ratio - RR = 0.540), and participating in body building to enhance self-esteem (RR = 0.423) or to enhance sport performance (RR = 0.545) had protective effects on amphetamine use. However, having university qualifications (RR = 1.843), using anabolic steroids (RR = 1.803) and participating in sport to maintain fitness (RR = 2.472) were linked to increased risk of amphetamine use. Well-educated bodybuilders were more likely to use amphetamines, and why this is so needs to be discovered. If further studies show that they are not aware of the dangers associated with amphetamine use, providing them with information should be considered.

  4. 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.

  5. Comparison of intranasal methamphetamine and d-amphetamine self-administration by humans

    Science.gov (United States)

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Johanson, Chris-Ellyn; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2012-01-01

    Aims Anecdotally, methamphetamine is considered to have a greater abuse potential compared to d-amphetamine, but there are no studies directly comparing self-administration of these drugs. This study characterized and compared self-administration as well as the mood, performance, and physiological effects of intranasal methamphetamine- and d-amphetamine. Design A randomized, double-blind, placebo-controlled, cross-over study. Setting An outpatient research unit at the New York State Psychiatric Institute. Participants Male recreational methamphetamine users (n = 13). Measurements Five 2-day blocks of sessions were conducted. On the first day of each block, participants “sampled” a single methamphetamine or d-amphetamine dose (0, 12, 50 mg/70 kg) and a monetary reinforcer ($5 or $20). Amphetamines plasma levels, cardiovascular, mood, and psychomotor performance effects were assessed before drug administration and repeatedly thereafter. On the second day of each block, participants chose between the sampled reinforcers (drug or money). Findings There were no significant differences between the drugs on the majority of measures. Under the $5 condition, both amphetamines dose-dependently increased self-administration, whereas under the $20 condition, few drug options were selected. Overall, participants selected more drug choices under the $5 condition compared with the $20 condition (41% versus 17%). Both drugs increased cardiovascular activity and “positive” mood, although methamphetamine produced more prominent effects on some measures (e.g., heart rate and ratings of ‘high’). Conclusions These data are consistent with previous findings suggesting that the two amphetamines produce a similar dose-related profile of acute effects in humans, with methamphetamine producing greater effects on some mood and cardiovascular measures. The amphetamines were self-administered equally indicating their equivalence for abuse potential. PMID:22050030

  6. Maintaining class, producing gender: enhancement discourses about amphetamine in entertainment media.

    Science.gov (United States)

    McKenna, Stacey A

    2011-11-01

    Since the 1930s, amphetamine has been used for a variety of socially and medically condoned purposes including personal and performance enhancement. In the contemporary U.S., although amphetamine and its derivatives share a history, similar chemical composition, and physiological and psychiatric effects, they are typically treated and researched as two distinct groups: illegally produced methamphetamine and prescription amphetamine. This study is an examination of the social meanings of these categories and their users as represented in popular media. To complement existing research on drug discourses in popular news media, this study analysed entertainment media: ten novels, three seasons of Breaking Bad, six television episodes, and eight movies. Media were coded inductively and deductively using tenets of critical discourse analysis and rhetorical criticism. The author identified discourses about user subject positions and ideologies pertaining to enhancement-related motivations for use. Two important themes emerged from this analysis that construct amphetamine use and users in ways that reflect, legitimize and reproduce class and gender ideologies. First, discourses illustrate that distinct meanings of methamphetamine versus prescription amphetamine are linked to expectations about the respective socioeconomic class and social status of their users. Second, the discourses reflect gendered values and ideals about productivity and sexuality. In reality, American cultural and political-economic contexts may encourage the use of amphetamine to meet a variety of social expectations and economic needs. However, many policy and prevention efforts surrounding amphetamine use disproportionately target methamphetamine users and women. Because policy and prevention efforts can be influenced as much by social values as by data, it is important to examine the many arenas in which social values are produced and disseminated. Copyright © 2011 Elsevier B.V. All rights

  7. Genetic variation of the ghrelin signalling system in individuals with amphetamine dependence.

    Directory of Open Access Journals (Sweden)

    Petra Suchankova

    Full Text Available The development of amphetamine dependence largely depends on the effects of amphetamine in the brain reward systems. Ghrelin, an orexigenic peptide, activates the reward systems and is required for reward induced by alcohol, nicotine, cocaine and amphetamine in mice. Human genetic studies have shown that polymorphisms in the pre-proghrelin (GHRL as well as GHS-R1A (GHSR genes are associated with high alcohol consumption, increased weight and smoking in males. Since the heritability factor underlying drug dependence is shared between different drugs of abuse, we here examine the association between single nucleotide polymorphisms (SNPs and haplotypes in the GHRL and GHSR, and amphetamine dependence. GHRL and GHSR SNPs were genotyped in Swedish amphetamine dependent individuals (n = 104 and controls from the general population (n = 310. A case-control analysis was performed and SNPs and haplotypes were additionally tested for association against Addiction Severity Interview (ASI composite score of drug use. The minor G-allele of the GHSR SNP rs2948694, was more common among amphetamine dependent individuals when compared to controls (pc  = 0.02. A significant association between the GHRL SNP rs4684677 and ASI composite score of drug use was also reported (pc  = 0.03. The haplotype analysis did not add to the information given by the individual polymorphisms. Although genetic variability of the ghrelin signalling system is not a diagnostic marker for amphetamine dependence and problem severity of drug use, the present results strengthen the notion that ghrelin and its receptor may be involved in the development of addictive behaviours and may thus serve as suitable targets for new treatments of such disorders.

  8. Short-term outcomes of mothers and infants exposed to antenatal amphetamines.

    Science.gov (United States)

    Oei, J; Abdel-Latif, M E; Clark, R; Craig, F; Lui, K

    2010-01-01

    To determine the short-term outcomes of newborn infants and mothers exposed to antenatal amphetamines in the state of New South Wales and the Australian Capital Territory during 2004. Amphetamine exposure was determined retrospectively using ICD-10 AM morbidity code searches of hospital medical records and from records of local drug and alcohol services. Records were reviewed on site. All public hospitals (n = 101) with obstetric services were included. Amphetamines were used by 200 (22.9%) of the 871 identified drug-using mothers. Most women (182, 91%) injected amphetamines intravenously. Compared with the other 669 drug users, amphetamine-using mothers were significantly more likely to use multiple classes of drugs (45.0% vs 7.8%), be subject to domestic violence (32.1% vs 17.5%), be homeless (14.8% vs 4.9%) and be involved with correctional services (19.8% vs 9.7%). The incidence of comorbid psychiatric illnesses were significantly higher (57.4% vs 41.7%) and their infants were more likely to be preterm (29.5% vs 20.4%), notified as children at risk (67.0% vs 32.8%), fostered before hospital discharge (14.5% vs 5.5%) and less likely to be breastfed (27.0% vs 41.6%). Amphetamine-exposed mothers and infants in public hospitals of NSW and the ACT are at significantly higher risk of adverse social and perinatal outcomes even when compared with mothers and infants exposed to other drugs of dependency. Increased vigilance for amphetamine exposure is recommended due to a high prevalence of use, especially in Australia, as a recreational drug.

  9. 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. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose administration of clobenzorex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    2001-04-01

    Clobenzorex (Asenlix) is an anorectic drug used as part of a weight-management program. The drug is metabolized by the body to amphetamine, which is then excreted in the urine, thus causing difficulty in interpretation of amphetamine-positive drug tests. Previous studies have shown that the parent drug and several metabolites are excreted in urine. Clobenzorex itself has been detected for as long as 29 h following administration of a single dose. However, the parent drug was not always detected in samples that contained amphetamine at > or =500 ng/mL, the administrative cutoff for a positive result. Consequently, the parent compound clobenzorex is not ideal for ascertaining whether the drug was the origin of the amphetamine. Several metabolites of clobenzorex have been shown to be detected for a longer period of time than the parent. One of these, a hydroxy metabolite, was shown to be detected for an extended period of time. In a study of urine samples provided following administration of a single 30-mg dose of this drug, 4-hydroxyclobenzorex could be detected for up to 91.5 h. More significantly, that study showed all samples that were positive for amphetamine also contained detectable amounts of 4-hydroxyclobenzorex. This metabolite proved to be easily detected and was typically found at higher levels than amphetamine in urine samples positive for amphetamine long after clobenzorex itself could no longer be detected. The present study analyzed samples from a controlled multidose administration (30 mg of clobenzorex daily for seven days) for the presence of 4-hydroxyclobenzorex. The analytical procedure used acid hydrolysis followed by liquid-liquid extraction and gas chromatographic-mass spectrometric analysis with monitoring of ions at m/z 125, 330, and 364 for 4-hydroxyclobenzorex and its 3-Cl regioisomer, which was used as an internal standard. Peak concentrations of 4-hydroxyclobenzorex ranged from 17,786 to 99,044 ng/mL. Most importantly, this study also

  11. Verbal memory improved by D-amphetamine: influence of the testing effect.

    Science.gov (United States)

    Zeeuws, Inge; Deroost, Natacha; Soetens, Eric

    2010-07-01

    The improvement of long-term retention of verbal memory after an acute administration of D-amphetamine in recall and recognition tasks has been ascribed to an influence of the drug on memory consolidation. Because recent research has demonstrated that intermediate testing is of overriding importance for retention, we investigated whether D-amphetamine modulates the repeated testing effect in verbal long-term recognition. Forty men participated in two double blind placebo controlled studies. In Experiment 1, we manipulated the number of recognition tests and in Experiment 2, we compared repeated with nonrepeated testing of the same items. Drug effects were observed on delayed tests only, leaving immediate recognition unaffected. Number of intermediate recognition tests and repeated testing of the same items were not affected by D-amphetamine. We conclude that the D-amphetamine memory enhancement is not related to the testing effect. This result supports that D-amphetamine modulates other aspects of the consolidation process, probably related to context effects. (c) 2010 John Wiley & Sons, Ltd.

  12. Associations Between Behavioral and Neural Correlates of Inhibitory Control and Amphetamine Reward Sensitivity.

    Science.gov (United States)

    Weafer, Jessica; Gorka, Stephanie M; Hedeker, Donald; Dzemidzic, Mario; Kareken, David A; Phan, K Luan; de Wit, Harriet

    2017-08-01

    Poor inhibitory control and sensitivity to drug reward are two significant risk factors for drug abuse. Although the two have been largely viewed as separate and independent risk factors, there is new evidence to suggest that they may be related at both the behavioral and neural level. This study examined associations between behavioral and neural correlates of inhibitory control and sensitivity to the subjective rewarding effects of amphetamine in humans. Healthy volunteers (n=63) first completed the stop signal task, a behavioral measure of inhibitory control. Then they participated in four sessions in which they received amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and arousal at regular intervals. Finally, a subset of participants (n=38) underwent an fMRI scan to assess neural correlates of inhibitory control. In the first phase of the study, participants with longer stop signal reaction time (SSRT) reported greater amphetamine-induced euphoria and stimulation than those with shorter SSRT. In the second phase, fMRI of response inhibition showed the expected activation in right prefrontal regions. Further, individuals who exhibited less activation in the right middle frontal gyrus during the inhibition task reported more euphoria during the amphetamine sessions. This study is the first to show associations between poor inhibitory control and amphetamine reward sensitivity at both behavioral and neural levels in humans. These findings extend our understanding of risk for drug abuse in individuals with poor inhibitory control and suggest novel targets for prevention efforts.

  13. The Relative Reinforcing Strength of Methamphetamine and d-Amphetamine in Monkeys Self-Administering Cocaine

    Science.gov (United States)

    Lile, Joshua A.; Charnigo, Richard J.; Nader, Michael A.

    2013-01-01

    Epidemiological data indicate that rates of methamphetamine misuse surpass those of d-amphetamine, but self-administration research in animals and humans has not typically demonstrated differences in their reinforcing effects. The present study used a within-session, exponentially-increasing progressive-ratio schedule and extended-access conditions to assess the relative reinforcing strength of d-amphetamine and methamphetamine in rhesus monkeys (n=5) trained to self-administer cocaine. A range of doses of methamphetamine (0.003–0.1 mg/kg/injection), d-amphetamine (0.003–0.1 mg/kg/injection) and cocaine (0.003–0.3 mg/kg/injection) was tested to capture the ascending and descending limbs of the dose-effect functions. Each drug functioned as a reinforcer, but the peak number of self-administered d-amphetamine injections was significantly lower compared to methamphetamine and cocaine; the peak number of self-administered injections of cocaine and methamphetamine did not differ. Although differences in availability and other social factors likely impact relative rates of abuse, the present data suggest that the greater reinforcing strength of methamphetamine contributes to its increased use compared to d-amphetamine. PMID:23907377

  14. Hollow-fiber liquid-phase microextraction of amphetamine-type stimulants in human hair samples.

    Science.gov (United States)

    do Nascimento Pantaleão, Lorena; Bismara Paranhos, Beatriz Aparecida Passos; Yonamine, Mauricio

    2012-09-07

    A fast method was optimized and validated in order to quantify amphetamine-type stimulants (amphetamine, AMP; methamphetamine, MAMP; fenproporex, FPX; 3,4-methylenedioxymethamphetamine, MDMA; and 3,4-methylenedioxyamphetamine, MDA) in human hair samples. The method was based in an initial procedure of decontamination of hair samples (50 mg) with dichloromethane, followed by alkaline hydrolysis and extraction of the amphetamines using hollow-fiber liquid-phase micro extraction (HF-LPME) in the three-phase mode. Gas chromatography-mass spectrometry (GC-MS) was used for identification and quantification of the analytes. The LoQs obtained for all amphetamines (around 0.05 ng/mg) were below the cut-off value (0.2 ng/mg) established by the Society of Hair Testing (SoHT). The method showed to be simple and precise. The intra-day and inter-day precisions were within 10.6% and 11.4%, respectively, with the use of only two deuterated internal standards (AMP-d5 and MDMA-d5). By using the weighted least squares linear regression (1/x²), the accuracy of the method was satisfied in the lower concentration levels (accuracy values better than 87%). Hair samples collected from six volunteers who reported regular use of amphetamines were submitted to the developed method. Drug detection was observed in all samples of the volunteers. Copyright © 2012 Elsevier B.V. All rights reserved.

  15. Exposure to Amphetamines Leads to Development of Amphetamine Type Stimulants Associated Cardiomyopathy (ATSAC).

    Science.gov (United States)

    Jafari Giv, Mahsa

    2017-01-01

    With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC. Several animal studies, case reports, case series and case-control studies support the association between ATS exposure and ATSAC. Oxidative stress, accelerated apoptosis, increased p53 activity, cardiomyocyte necrosis, perfusion defects, fatty acid toxicity, altered gene expression, abnormal cardiac protein synthesis and function in addition to defects in intracellular calcium hemostasis present themselves as likely mechanisms of cardiotoxicity in ATSAC. Majority of patients with ATSAC were found to be male, young and presented late with severe dilated cardiomyopathy. Female ATS users predominantly develop Takotsubo type of ATSAC and in particular its atypical basal variant. Overall, cessation of ATS exposure seems to be associated with some degree of reversibility and recovery in ATSAC sufferers.

  16. 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.; Oliveira, Tiago F.; 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...

  17. Hypoinsulinemia regulates amphetamine-induced reverse transport of dopamine.

    Directory of Open Access Journals (Sweden)

    Jason M Williams

    2007-10-01

    Full Text Available The behavioral effects of psychomotor stimulants such as amphetamine (AMPH arise from their ability to elicit increases in extracellular dopamine (DA. These AMPH-induced increases are achieved by DA transporter (DAT-mediated transmitter efflux. Recently, we have shown that AMPH self-administration is reduced in rats that have been depleted of insulin with the diabetogenic agent streptozotocin (STZ. In vitro studies suggest that hypoinsulinemia may regulate the actions of AMPH by inhibiting the insulin downstream effectors phosphotidylinositol 3-kinase (PI3K and protein kinase B (PKB, or Akt, which we have previously shown are able to fine-tune DAT cell-surface expression. Here, we demonstrate that striatal Akt function, as well as DAT cell-surface expression, are significantly reduced by STZ. In addition, our data show that the release of DA, determined by high-speed chronoamperometry (HSCA in the striatum, in response to AMPH, is severely impaired in these insulin-deficient rats. Importantly, selective inhibition of PI3K with LY294002 within the striatum results in a profound reduction in the subsequent potential for AMPH to evoke DA efflux. Consistent with our biochemical and in vivo electrochemical data, findings from functional magnetic resonance imaging experiments reveal that the ability of AMPH to elicit positive blood oxygen level-dependent signal changes in the striatum is significantly blunted in STZ-treated rats. Finally, local infusion of insulin into the striatum of STZ-treated animals significantly recovers the ability of AMPH to stimulate DA release as measured by high-speed chronoamperometry. The present studies establish that PI3K signaling regulates the neurochemical actions of AMPH-like psychomotor stimulants. These data suggest that insulin signaling pathways may represent a novel mechanism for regulating DA transmission, one which may be targeted for the treatment of AMPH abuse and potentially other dopaminergic disorders.

  18. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

    Science.gov (United States)

    Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

    2013-01-01

    Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

  19. 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.

  20. Effects of modafinil and amphetamine on sleep-wake cycle after sleep deprivation in cats.

    Science.gov (United States)

    Hou, Y P; Lin, J S

    1999-09-01

    The effects of modafinil and amphetamine on sleep-wake cycle and cortical power spectrum were assessed in the cats before and after sleep deprivation. The sleep deprivation in the cats was used with the water tank technique. Cats were administrated with modafinil (5 mg.kg-1 p.o.) or amphetamine (1 mg.kg-1) before and after sleep deprivation. The waking effect of 8-10 h induced by modafinil before and after sleep deprivation was similar and was not followed by an increase in sleep rebound. On the contrary, the arousal effect about 8 h evoked by amphetamine after sleep deprivation was less lasting than that of 10-12 h observed in normal conditions and followed by an amplified rebound in both deep slow wave sleep and paradoxical sleep. These results suggest the efficiency of modafinil against somnolence and hypersomnia without increasing subsequent sleep.

  1. 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.

  2. 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...

  3. Sweet taste liking is associated with subjective response to amphetamine in women but not men.

    Science.gov (United States)

    Weafer, Jessica; Lyon, Nicholas; Hedeker, Donald; de Wit, Harriet

    2017-11-01

    Preference for sweet taste rewards has been linked to the propensity for drug use in both animals and humans. Here, we tested the association between sweet taste liking and sensitivity to amphetamine reward in healthy adults. We hypothesized that sweet likers would report greater euphoria and stimulation following D-amphetamine (20 mg) compared to sweet dislikers. Men (n = 36) and women (n = 34) completed a sweet taste test in which they rated their liking of various concentrations of sucrose and filtered water (0.05, 0.10, 0.21, 0.42, and 0.83 M). Participants who preferred the highest concentration were classified as "sweet likers." All others were classified as "sweet dislikers." They then completed four sessions in which they received D-amphetamine (20 mg) and placebo in alternating order, providing self-report measures of euphoria and stimulation on the Addiction Research Center Inventory (ARCI) at regular intervals. We conducted linear mixed effects models to examine relationships between sweet liking and drug-induced euphoria and stimulation. Sweet likers reported significantly greater amphetamine-induced euphoria than did sweet dislikers among women. By contrast, sweet liking was not associated with amphetamine response in men. No associations with stimulation were observed. The association between sweet preference and amphetamine response in women is consistent with animal studies linking sweet taste preference and drug reward and also fits with observations that individuals who use drugs show a preference for sweet tastes. Whether the sex difference is related to circulating hormones, or other variables, remains to be determined.

  4. Serotonin in the ventral hippocampus modulates anxiety-like behavior during amphetamine withdrawal.

    Science.gov (United States)

    Tu, W; Cook, A; Scholl, J L; Mears, M; Watt, M J; Renner, K J; Forster, G L

    2014-12-05

    Withdrawal from amphetamine is associated with increased anxiety and sensitivity to stressors which are thought to contribute to relapse. Rats undergoing amphetamine withdrawal fail to exhibit stress-induced increases in serotonin (5-HT) release in the ventral hippocampus and show heightened anxiety-like behaviors. Therefore, we tested the hypothesis that reducing 5-HT levels in the ventral hippocampus is a causal mechanism in increasing anxiety-like behaviors during amphetamine withdrawal. First, we tested whether reducing 5-HT levels in the ventral hippocampus directly increases anxiety behavior. Male rats were bilaterally infused with 5,7-dihydroxytryptamine (5,7-DHT) into the ventral hippocampus, which produced a 83% decrease in ventral hippocampus 5-HT content, and were tested on the elevated plus maze (EPM) for anxiety-like behavior. Reducing ventral hippocampus 5-HT levels decreased the time spent in the open arms of the maze, suggesting that diminished ventral hippocampus 5-HT levels increases anxiety-like behavior. Next, we tested whether increasing 5-HT levels in the ventral hippocampus reverses anxiety behavior exhibited by rats undergoing amphetamine withdrawal. Rats were treated daily with either amphetamine (2.5-mg/kg, i.p.) or saline for 2weeks, and at 2weeks withdrawal, were infused with the selective serotonin reuptake inhibitor paroxetine (0.5μM) bilaterally into the ventral hippocampus and tested for anxiety-like behavior on the EPM. Rats pre-treated with amphetamine exhibited increased anxiety-like behavior on the EPM. This effect was reversed by ventral hippocampus infusion of paroxetine. Our results suggest that 5-HT levels in the ventral hippocampus are critical for regulating anxiety behavior. Increasing 5-HT levels during withdrawal may be an effective strategy for reducing anxiety-induced drug relapse. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Reece, Albert Stuart; Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

    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. 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. 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 p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA) 2 and (CA) 3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001). These results show that subacute exposure to amphetamines 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.

  6. Cdk5 Is Essential for Amphetamine to Increase Dendritic Spine Density in Hippocampal Pyramidal Neurons

    Directory of Open Access Journals (Sweden)

    Soledad Ferreras

    2017-11-01

    Full Text Available Psychostimulant drugs of abuse increase dendritic spine density in reward centers of the brain. However, little is known about their effects in the hippocampus, where activity-dependent changes in the density of dendritic spine are associated with learning and memory. Recent reports suggest that Cdk5 plays an important role in drug addiction, but its role in psychostimulant’s effects on dendritic spines in hippocampus remain unknown. We used in vivo and in vitro approaches to demonstrate that amphetamine increases dendritic spine density in pyramidal neurons of the hippocampus. Primary cultures and organotypic slice cultures were used for cellular, molecular, pharmacological and biochemical analyses of the role of Cdk5/p25 in amphetamine-induced dendritic spine formation. Amphetamine (two-injection protocol increased dendritic spine density in hippocampal neurons of thy1-green fluorescent protein (GFP mice, as well as in hippocampal cultured neurons and organotypic slice cultures. Either genetic or pharmacological inhibition of Cdk5 activity prevented the amphetamine–induced increase in dendritic spine density. Amphetamine also increased spine density in neurons overexpressing the strong Cdk5 activator p25. Finally, inhibition of calpain, the protease necessary for the conversion of p35 to p25, prevented amphetamine’s effect on dendritic spine density. We demonstrate, for the first time, that amphetamine increases the density of dendritic spine in hippocampal pyramidal neurons in vivo and in vitro. Moreover, we show that the Cdk5/p25 signaling and calpain activity are both necessary for the effect of amphetamine on dendritic spine density. The identification of molecular mechanisms underlying psychostimulant effects provides novel and promising therapeutic approaches for the treatment of drug addiction.

  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. The acetylcholinesterase inhibitor galantamine inhibits d-amphetamine-induced psychotic-like behavior in Cebus monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Werge, Thomas; Fink-Jensen, Anders

    2007-01-01

    allosterically potentiates nicotinic receptor stimulation. To this end, we investigated its ability to antagonize d-amphetamine-induced psychotic-like behavior in extrapyramidal side effects (EPS)-primed Cebus monkeys. Galantamine inhibited d-amphetamine-induced unrest, arousal, and stereotypy. Side effects...... such as emesis, sedation, and EPS were minor or not existing. The results indicate that AChE inhibitors have antipsychotic potentials and suggest that clinical trials investigating antipsychotic effects of AChE inhibitors as monotherapy would be of interest....

  9. The Impact of Illicit Use of Amphetamine on Male Sexual Functions.

    Science.gov (United States)

    Chou, Nan-Hua; Huang, Yung-Jui; Jiann, Bang-Ping

    2015-08-01

    Data concerning the impact of amphetamine on male sexual functions are limited, although amphetamine has been used as an aphrodisiac. This cross-sectional study was to assess the impact of illicit use of amphetamine on male sexual functions. Male illicit drug users in a Drug Abstention and Treatment Center were recruited to complete a self-administered questionnaire, and data were compared with age-matched controls. The International Index of Erectile Function (IIEF) and global assessment questions were used to assess sexual functions. Of 1,159 amphetamine mono-illicit drug users, the mean age was 31.9 ± 7.5 (18-57) years, and mean duration of drug use was 30.7 ± 52.2 (median 9, range 0.1-252) months. Half of them reported that drug use had no impact on their sexual functions. The other half reported drug impacts as reduced erectile rigidity and sexual life satisfaction, enhanced orgasmic intensity, and prolonged ejaculation latency time more often than the opposite effects, while they reported enhanced or reduced effect equally on sexual desire. Dosing frequency of amphetamine was associated with its impact on sexual functions, but duration of its use had little association with that. Compared with 211 age-matched controls, the amphetamine mono-illicit drug users had lower IIEF scores in the domains of erectile function, orgasmic function, and overall satisfaction, but there are no significant differences in intercourse satisfaction and sexual desire scores. The prevalence of erectile dysfunction (ED) was significantly higher in the drug users than in the controls (29.3% vs. 11.9%). The odds ratio of ED for amphetamine use was 2.1 (95% confidence interval 1.2-3.6) after adjustment for other risk factors. The impact of illicit use of amphetamine on male sexual functions varied among users, and their ED prevalence was higher than the controls. © 2015 International Society for Sexual Medicine.

  10. Amphetamines for attention deficit hyperactivity disorder (ADHD) in children and adolescents.

    Science.gov (United States)

    Punja, Salima; Shamseer, Larissa; Hartling, Lisa; Urichuk, Liana; Vandermeer, Ben; Nikles, Jane; Vohra, Sunita

    2016-02-04

    Attention deficit hyperactivity disorder (ADHD) is one of the most common psychiatric conditions affecting children and adolescents. Amphetamines are among the most commonly prescribed medications to manage ADHD. There are three main classes of amphetamines: dexamphetamine, lisdexamphetamine and mixed amphetamine salts, which can be further broken down into short- and long-acting formulations. A systematic review assessing their efficacy and safety in this population has never been conducted. To assess the efficacy and safety of amphetamines for ADHD in children and adolescents. In August 2015 we searched CENTRAL, Ovid MEDLINE, Embase, PsycINFO, ProQuest Dissertation and Theses, and the Networked Digital Library of Theses and Dissertations. We also searched ClinicalTrials.gov, and checked the reference lists of relevant studies and reviews identified by the searches. No language or date restrictions were applied. Parallel-group and cross-over randomized controlled trials (RCTs) comparing amphetamine derivatives against placebo in a pediatric population (ADHD. Two authors independently extracted data on participants, settings, interventions, methodology, and outcomes for each included study. For continuous outcomes, we calculated the standardized mean difference (SMD) and for dichotomous outcomes we calculated the risk ratio (RR). Where possible, we conducted meta-analyses using a random-effects model. We also performed a meta-analysis of the most commonly reported adverse events in the primary studies. We included 23 trials (8 parallel-group and 15 cross-over trials), with 2675 children aged three years to 17 years. All studies compared amphetamines to placebo. Study durations ranged from 14 days to 365 days, with the majority lasting less than six months. Most studies were conducted in the United States; three studies were conducted across Europe. We judged 11 included studies to be at a high risk of bias due to insufficient blinding methods, failing to account

  11. Behavioral sensitization and cross-sensitization between methylphenidate amphetamine, and 3-4, methylenedioxymethamphetamine (MDMA) in female SD rats

    Science.gov (United States)

    Yang, Pamela B.; Atkins, Kristal D.; Dafny, Nachum

    2014-01-01

    The psychostimulants amphetamine and methylphenidate (MPD / Ritalin) are the drugs most often used to treat attention deficit hyperactivity disorder (ADHD). In addition, students of all ages take these drugs to improve academic performance but also abuse them for pleasurable enhancement. In addition, other psychostimulants such 3,4 methylenedioxymethamphetamine (MDMA / ecstasy) are used / abused for similar objectives. One of the experimental markers for the potential of a drug to produce dependence is its ability to induce behavioral sensitization and cross sensitization with other drugs of abuse. The objective of this study is to use identical experimental protocols and behavioral assays to compare in female rats the effects of amphetamine, MPD and MDMA on locomotor activity and to determine if they induce behavioral sensitization and/or cross sensitization with each other. The main findings of this study are 1. Acute amphetamine, MPD and MDMA all elicited increases in locomotor activity. 2. Chronic administration of an intermediate dose of amphetamine or MPD elicited behavioral sensitization. 3. Chronic administration of MDMA elicited behavioral sensitization in some animals and behavioral tolerance in others. 4. Cross sensitization between MPD and amphetamine was observed. 5. MDMA did not show either cross sensitization or cross tolerance with amphetamine. In conclusion, these results suggest that MDMA act by different mechanisms compared to MPD and amphetamine. PMID:21549116

  12. Glucostatic regulation of (+)-[3H]amphetamine binding in the hypothalamus: correlation with Na+, K+-ATPase activity

    International Nuclear Information System (INIS)

    Angel, I.; Hauger, R.L.; Luu, M.D.; Giblin, B.; Skolnick, P.; Paul, S.M.

    1985-01-01

    Preincubation of rat hypothalamic slices in glucose-free Krebs-Ringer buffer (37 0 C) resulted in a time-dependent decrease in specific (+)-[ 3 H]amphetamine binding in the crude synaptosomal fraction prepared from these slices. The addition of D-glucose resulted in a dose- and time-dependent stimulation of (+)-[ 3 H]amphetamine binding, whereas incubations with L-glucose, 2-deoxy-D-glucose, or 3-O-methyl-D-glucose failed to increase the number of (+)-[ 3 H]amphetamine binding sites. Ouabain potently inhibited the glucose-induced stimulation of (+)-[ 3 H]amphetamine binding, suggesting the involvement of Na + , K + -ATPase. Preincubation of hypothalamic slices with glucose also resulted in an increase in Na + ,K + -ATPase activity and the number of specific high-affinity binding sites for [ 3 H]ouabain, and a good correlation was observed between the glucose-stimulated increase in (+)-[ 3 H]amphetamine and [ 3 H]ouabain binding. These data suggest that the (+)-[ 3 H]amphetamine binding site in hypothalamus, previously linked to the anorectic actions of various phenylethylamines, is regulated both in vitro and in vivo by physiological concentrations of glucose. Glucose and amphetamine appear to interact at common sites in the hypothalamus to stimulate Na + ,K + -ATPase activity, and the latter may be involved in the glucostatic regulation of appetite

  13. Mazindol and amphetamine as inhibitors of the uptake and releasers of 3H-dopamine by rat striatal synaptosomes.

    Science.gov (United States)

    Carruba, M O; Picotti, G B; Zambotti, F; Mantegazza, P

    1977-05-01

    The effects of mazindol, amphetamine and fenfluramine on uptake and release of 3H-DA by synaptosomes were studied in different systems. In in vitro incubations of 3H-DA with synaptosomes isolated from the caudate nucleus of the rat, mazindol inhibited the uptake of the radioactivity more potently than did amphetamine. When the synaptosomes were isolated from the caudate nuclei of rats treated in vivo with either mazindol or amphetamine, the uptake of 3H-DA during in vitro incuation was lower with synaptosomes of amphetamine-treated rats than with those of mazindol-treated rats. When synaptosomes of untreated rats were prelabelled with 3H-DA and incubated in the presence of amphetamine or of mazindol, amphetamine caused a greater release of radioactivity than did mazindol. Fenfluramine was without activity in all these systems. In spite of the quantitative differences, both amphetamine and mazindol appear to have similar effects on uptake and release of dopamine, and this may account for their analogous pharmacological profile.

  14. Cannabis and Amphetamine Use and Associated Factors among School-Going Adolescents in Nine African Countries

    Science.gov (United States)

    Peltzer, Karl; Pengpid, Supa

    2018-01-01

    The aim of this study was to assess the prevalence of cannabis and amphetamine use and associated factors among adolescents in nine African countries. We analyzed cross-sectional data from 25,372 adolescents (mean age 14.3 years, SD = 1.6) from nine African countries that participated in the Global School-Based Student Health Survey (GSHS) in…

  15. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.

    Science.gov (United States)

    Achterberg, E J Marijke; Trezza, Viviana; Siviy, Stephen M; Schrama, Laurens; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J

    2014-04-01

    Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.

  16. 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...

  17. 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...

  18. 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...

  19. [Pathomorphological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of a street drugs brand].

    Science.gov (United States)

    Ruzin, G P; Tkachenko, O V; Miroshnichenko, M S; Pliten', O N

    2013-06-01

    In the article the authors present the pathological features of chronic toxic osteomyelitis in drug addicts taking amphetamine of handicraft production (pervitin, vint). It is shown that this pathology is characterized by the predominance of marked degenerative, necrotic and inflammatory changes over the reparative processes.

  20. Effects of OROS-MPH Versus Dl-Amphetamine-XR on Driving Performance of ADHD Adolescents

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2006-10-01

    Full Text Available Driving performance of 35 adolescent ADHD patients (19 boys/16 girls; mean age 17.8 years on a driving simulator was compared while taking OROS methylphenidate (Concerta, 72 mg, mixed dl-amphetamine salts (Adderall XR, 30 mg, or placebo in a randomized, double-blind, crossover study at University of Virginia, Charlottesville.

  1. [Acute poisoning with weight-loss dietary supplement falsely suggesting the use of amphetamine].

    Science.gov (United States)

    Łukasik-Głebocka, Magdalena; Sommerfeld, Karina; Tezyk, Artur; Zielińska-Psuja, Barbara

    2013-01-01

    We report a case of abuse of weight-loss dietary supplement in 27-year-old man, with characteristic for amphetamine sympathomimetic symptoms and positive analysis of this drug in the urine by immunoassay method (FPIA; Axsym, Abbott). However positive result was not confirmed by liquid chromatography coupled with tandem mass spectrometry (LC-MS-MS). The patient ate nine tablets of the Thermal Pro with declared composition of caffeine (250 mg), bitter orange (200 mg), beta-phenylethylamine (100 mg), willow bark (75 mg), Cayenne pepper (40 mg), 1,3-dimethyloamyloamine (DMAA, 35 mg), gooseberry extract (20 mg), bergamot orange (20 mg), black pepper (5 mg), after two-month period of regular consumption at dose of 2-3 capsules per day. After 4 hours, during admission to the Department of Toxicology, patient manifested typical sympathomimetic symptoms: anxiety, agitation, pale skin, sweats, tachycardia 120/min, mydriasis. Following the outcome of detecting amphetamine/methamphetamine in the patient's urine at 2377 ng/mL concentration using FPIA method, drug intoxication was suspected. It was considered that the ingestion was intentional or unconscious of adulterated dietary supplement. In view of the strong opposition of the patient, who denied any use of psychoactive substances, it was decided to re-examine collected speciments. The liquid chromatography coupled to tandem mass spectrometry (LC-MS-MS) method did not confirm the presence of amphetamine in the patient's blood and urine. Based on the composition of dietary supplements for substances which could be responsible for the positive amphetamine result in urine by FPIA method and available literature data, it was concluded that the substances that may react in the immunoassay could be dimethylamyloamine (DMAA, geranamine) or bitter orange components. False positive urinalysis towards amphetamine/methamphetamine by immunoassay and presence of sympathomimetic effects may contribute to a false diagnosis of this drug

  2. Amphetamine-related myocardial infarction in a 42-year old man

    Directory of Open Access Journals (Sweden)

    Anna Smędra

    2016-03-01

    Full Text Available Myocardial infarction is an infrequent condition in young adults. In most cases, it occurs due to causes other than atherosclerosis of the coronary arteries, including blood hypercoagulability, congenital anomalies of the coronary arteries, their inflammation or spasm induced by amphetamine or cocaine use. Amphetamine and its derivatives, via increasing the levels of epinephrine, serotonin and dopamine in the central nervous system, exert their effect also on the cardiovascular system, causing coronary spasm, enhancing platelet aggregation and inducing tachyarrhythmias. The paper presents a case of a 42-year-old man admitted to the emergency department because of emaciation and dehydration. The man was conscious, without contact, with a significant elevation of body temperature and tachycardia. On the basis of examinations, a fresh infarction of the anterolateral wall of the heart was diagnosed and the patient was transferred to a cardiac intensive care unit. There, laboratory tests revealed significantly elevated markers of myocardial necrosis and the presence of amphetamine in blood and urine. In spite of the institution of treatment the patient developed cardiorespiratory arrest. Advanced resuscitation procedures were undertaken, however, they proved unsuccessful. The presence of an infarction focus was confirmed in autopsy. Toxicological analysis of the blood for the presence of alcohol-like substances detected amphetamine at a concentration of 269.5 ng/ml. After examining the complete body of evidence it was established that the patient had died of acute cardiorespiratory failure secondary to an extensive fresh myocardial infarction. As indicated by the accumulated data, the most probable cause of myocardial infarction was amphetamine poisoning.

  3. 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.

  4. 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...

  5. 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. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. Breakingtheice: A protocol for a randomised controlled trial of an internet-based intervention addressing amphetamine-type stimulant use

    Directory of Open Access Journals (Sweden)

    Tait Robert J

    2012-06-01

    Full Text Available Abstract Background The prevalence of amphetamine-type stimulant use is greater than that of opioids and cocaine combined. Currently, there are no approved pharmacotherapy treatments for amphetamine-type stimulant problems, but some face-to-face psychotherapies are of demonstrated effectiveness. However, most treatment services focus on alcohol or opioid disorders, have limited reach and may not appeal to users of amphetamine-type stimulants. Internet interventions have proven to be effective for some substance use problems but none has specifically targeted users of amphetamine-type stimulants. Design/method The study will use a randomized controlled trial design to evaluate the effect of an internet intervention for amphetamine-type stimulant problems compared with a waitlist control group. The primary outcome will be assessed as amphetamine-type stimulant use (baseline, 3 and 6 months. Other outcomes measures will include ‘readiness to change’, quality of life, psychological distress (K-10 score, days out of role, poly-drug use, help-seeking intention and help-seeking behavior. The intervention consists of three modules requiring an estimated total completion time of 90 minutes. The content of the modules was adapted from face-to-face clinical techniques based on cognitive behavior therapy and motivation enhancement. The target sample is 160 men and women aged 18 and over who have used amphetamine-type stimulants in the last 3 months. Discussion To our knowledge this will be the first randomized controlled trial of an internet intervention specifically developed for users of amphetamine-type stimulants. If successful, the intervention will offer greater reach than conventional therapies and may engage clients who do not generally seek treatment from existing service providers. Trial registration Australian and New Zealand Clinical Trials Registry (http://www.anzctr.org.au/ ACTRN12611000947909

  7. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys

    OpenAIRE

    Banks, Matthew L.; Smith, Douglas A.; Kisor, David F.; Poklis, Justin L.

    2015-01-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphet...

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Effects of amphetamine and cocaine on the development of acute experimental allergic encephalomyelitis in Lewis rats.

    Science.gov (United States)

    Núñez, María J; Balboa, José; Rey-Méndez, Manuel; Brenlla, Julio; González-Peteiro, Mercedes; Rodrigo, Elena; Freire-Garabal, Manuel

    2007-08-01

    The present experiment deals with the effects of amphetamine and cocaine on the development and course of experimental allergic encephalomyelitis (EAE) induced in Lewis rats. Rats were immunized at the age of eight weeks with purified myelin basic protein isolated from guinea pig brain in complete Freund's adjuvant. Drug administration and recording of EAE clinical signs was performed daily since day 1 post-immunization (PI). On day 14 and 28 PI, six rats per group were bled and sacrificed. Spinal cord was examined histologically for EAE lesions. In vivo administration of 0.5 and 1 mg/Kg of amphetamine or cocaine resulted in a dose-related enhancement of neurological and histological signs of acute EAE in comparison with control rats. Both drugs caused a reduction of latent period together with a delayed regression of neurological signs along with an increase in inflammation in the central nervous system in comparison with placebo. Human & Experimental Toxicology (2007) 26, 637-643.

  10. 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.

  11. Amphetamine primes enhanced motivation toward uncertain choices in rats with genetic alcohol preference.

    Science.gov (United States)

    Oinio, Ville; Sundström, Mikko; Bäckström, Pia; Uhari-Väänänen, Johanna; Kiianmaa, Kalervo; Raasmaja, Atso; Piepponen, Petteri

    2018-02-09

    Comorbidity with gambling disorder (GD) and alcohol use disorder (AUD) is well documented. The purpose of our study was to examine the influence of genetic alcohol drinking tendency on reward-guided decision making behavior of rats and the impact of dopamine releaser D-amphetamine on this behavior. In this study, Alko alcohol (AA) and Wistar rats went through long periods of operant lever pressing training where the task was to choose the profitable of two options. The lever choices were guided by different-sized sucrose rewards (one or three pellets), and the probability of gaining the larger reward was slowly changed to a level where choosing the smaller reward would be the most profitable in the long run. After training, rats were injected (s.c.) with dopamine releaser D-amphetamine (0.3, 1.0 mg/kg) to study the impact of rapid dopamine release on this learned decision making behavior. Administration of D-amphetamine promoted unprofitable decision making of AA rats more robustly when compared to Wistar rats. At the same time, D-amphetamine reduced lever pressing responses. Interestingly, we found that this reduction in lever pressing was significantly greater in Wistar rats than in AA rats and it was not linked to motivation to consume sucrose. Our results indicate that conditioning to the lever pressing in uncertain environments is more pronounced in AA than in Wistar rats and indicate that the reinforcing effects of a gambling-like environment act as a stronger conditioning factor for rats that exhibit a genetic tendency for high alcohol drinking.

  12. 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.

  13. 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.

  14. A triazolam/amphetamine dose-effect interaction study: dissociation of effects on memory versus arousal.

    Science.gov (United States)

    Mintzer, Miriam Z; Griffiths, Roland R

    2007-06-01

    In addition to producing robust memory impairment, benzodiazepines also induce marked sedation. Thus, it is possible that the observed amnestic effects are secondary to more global sedative effects and do not reflect a specific primary benzodiazepine effect on memory mechanisms. The objective was to use the nonspecific stimulant d-amphetamine to dissociate the sedative and memory-impairing effects of the benzodiazepine triazolam. Single oral doses of placebo, triazolam alone (0.25, 0.50 mg/70 kg), d-amphetamine sulfate alone (20, 30 mg/70 kg), and triazolam (0.25, 0.50 mg/70 kg) and d-amphetamine sulfate (20, 30 mg/70 kg) conjointly (at all dose combinations) were administered to 18 healthy adult participants across nine sessions in a double-blind, staggered-dosing, crossover design. In addition to standard data analyses, analyses were also conducted on z-score standardized data, enabling effects to be directly compared across measures. Relative to the sedative measures, the memory measures generally exhibited a pattern of less reversal of triazolam's effects by d-amphetamine. The memory measures ranged in degree of reversal such that the most reversal was observed for reaction time on the n-back working memory task, and the least reversal was observed for accuracy on the Sternberg working memory task, with most measures showing an overall pattern of partial reversal. Benzodiazepines have specific effects on memory that are not merely a by-product of the drugs' sedative effects, and the degree to which sedative effects contribute to the amnestic effects varies as a function of the particular memory process being assessed.

  15. A comparison of tyrosine against placebo, phentermine, caffeine, and D-amphetamine during sleep deprivation.

    Science.gov (United States)

    Waters, William F; Magill, Richard A; Bray, George A; Volaufova, Julia; Smith, Steven R; Lieberman, Harris R; Rood, Jennifer; Hurry, Mark; Anderson, Tai; Ryan, Donna H

    2003-08-01

    Sleep deprivation can impair alertness and cognitive and motor performance. We hypothesized that the amino acid tyrosine might reduce deleterious effects of sleep deprivation. Seventy-six healthy males, age 18-35 years, participated in a four-day protocol that included a habituation night, a baseline night, a 40.5 h period without sleep, and a recovery night. Tyrosine 150 mg/kg, caffeine 300 mg/70 kg, phentermine 37.5 mg, D-amphetamine 20 mg and placebo were administered in a double-blind, randomized fashion to compare their effects on the time it took to fall asleep, on endocrine responses during sleep deprivation, and on sleep quantity, quality and architecture as measured by polysomnography during recovery sleep. When given after 36 h without sleep, tyrosine had no significant effect on any parameter of sleep. D-amphetamine produced marked decrease in sleep drive but caused deleterious effects on many aspects of recovery sleep. Still, D-amphetamine was associated with increased alertness on the first recovery day. Phentermine and caffeine both decreased sleep drive during sleep deprivation, but phentermine impaired rapid-eye-movement (REM) recovery sleep. Tyrosine (when compared to placebo) had no effect on any sleep related measure, but it did stimulate prolactin release.

  16. Dopamine Development in the Mouse Orbital Prefrontal Cortex Is Protracted and Sensitive to Amphetamine in Adolescence.

    Science.gov (United States)

    Hoops, Daniel; Reynolds, Lauren M; Restrepo-Lozano, Jose-Maria; Flores, Cecilia

    2018-01-01

    The prefrontal cortex (PFC) is divided into subregions, including the medial and orbital prefrontal cortices. Dopamine connectivity in the medial PFC (mPFC) continues to be established throughout adolescence as the result of the continuous growth of axons that innervated the nucleus accumbens (NAcc) prior to adolescence. During this period, dopamine axons remain vulnerable to environmental influences, such as drugs used recreationally by humans. The developmental trajectory of the orbital prefrontal dopamine innervation remains almost completely unstudied. Nonetheless, the orbital PFC (oPFC) is critical for some of the most complex functions of the PFC and is disrupted by drugs of abuse, both in adolescent humans and rodents. Here, we use quantitative neuroanatomy, axon-initiated viral-vector recombination, and pharmacology in mice to determine the spatiotemporal development of the dopamine innervation to the oPFC and its vulnerability to amphetamine in adolescence. We find that dopamine innervation to the oPFC also continues to increase during adolescence and that this increase is due to the growth of new dopamine axons to this region. Furthermore, amphetamine in adolescence dramatically reduces the number of presynaptic sites on oPFC dopamine axons. In contrast, dopamine innervation to the piriform cortex is not protracted across adolescence and is not impacted by amphetamine exposure during adolescence, indicating that dopamine development during adolescence is a uniquely prefrontal phenomenon. This renders these fibers, and the PFC in general, particularly vulnerable to environmental risk factors during adolescence, such as recreational drug use.

  17. 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.

  18. Presentation of regional cerebral blood flow in amphetamine abusers by 99Tcm-HMPAO brain SPECT

    International Nuclear Information System (INIS)

    Kao, C.H.; Wang, S.J.; Yeh, S.H.

    1994-01-01

    The aim of this study was to describe the effectiveness of 99 Tc m -hexamethylpropyleneamine oxime ( 99 Tc 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 99 Tc 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, 99 Tc m -HMPAO brain SPECT is a sensitive but not specific test for neuropsychogenic abnormalities associated with amphetamine abuse. (Author)

  19. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo

    Science.gov (United States)

    Liu, Christina H.; Yang, Jinsheng; Ren, Jia Q.; Liu, Charng-Ming; You, Zerong; Liu, Philip K.

    2013-01-01

    How amphetamine affects the neuroglia in living brains is not well understood. In an effort to elucidate this effect, we investigated neuroglia in response to amphetamine exposure using antisense (AS) or sense (S) phosphorothioate-modified oligodeoxynucleotide (sODN) sequences that correspond to glial fibrillary acidic protein (GFAP) mRNA (AS-gfap or S-gfap, respectively) expression. The control is a random-sequence sODN (Ran). Using cyanine 5.5-superparamagnetic iron oxide nanoparticle (Cy5.5-SPION) labeling and fluorescent microscopy, we demonstrated that living neural progenitor cells (PC-12.1), as well as the cells in fresh brain slices and intact brains of male C57BL6 mice, exhibited universal uptake of all of the sODNs but rapidly excluded all sODN-Ran and most S-gfap. Moreover, transmission electron microscopy revealed electron-dense nanoparticles only in the neuroglia of normal or transgenic mice [B6;DBA-Tg(Fos-tTA, Fos-EGFP*)1MmayTg(tetO-lacZ,tTA*)1Mmay/J] that had been administered AS-gfap or Cy5.5-SPION-gfap. Subtraction R2* maps from mice with acute and chronic amphetamine exposure demonstrated, validated by postmortem immunohistochemistry, a reduction in striatal neuroglia, with gliogenesis in the subventricular zone and the somatosensory cortex in vivo. The sensitivity of our unique gene transcript targeted MRI was illustrated by a positive linear correlation (r2=1.0) between in vivo MRI signal changes and GFAP mRNA copy numbers determined by ex vivo quantitative RT-PCR. The study provides direct evidence for targeting neuroglia by antisense DNA-based SPION-gfap that enables in vivo MRI of inaccessible tissue with PCR sensitivity. The results enable us to conclude that amphetamine induces toxicity to neuroglia in vivo, which may cause remodeling or reconnectivity of neuroglia.—Liu, C. H., Yang, J., Ren, J. Q., Liu, C.-M., You, Z., Liu, P. K. MRI reveals differential effects of amphetamine exposure on neuroglia in vivo. PMID:23150521

  20. Chronic variable stress prevents amphetamine-elicited 50-kHz calls in rats with low positive affectivity.

    Science.gov (United States)

    Kõiv, Kadri; Metelitsa, Mait; Vares, Marten; Tiitsaar, Kai; Raudkivi, Karita; Jaako, Külli; Vulla, Kaspar; Shimmo, Ruth; Harro, Jaanus

    2016-04-01

    The relationship between stress response and positive affective states is thought to be bidirectional: whilst stress can lead to a blunted hedonic response, positive affect reduces the negative effects of stress. We have previously shown that persistently high positive affectivity as measured by 50-kHz ultrasonic vocalizations (USVs) is protective against chronic variable stress (CVS). The present study examined the effect of CVS on 50-kHz USVs elicited by amphetamine administration, simultaneously considering the stable inter-individual differences in positive affectivity. Forty juvenile male Wistar rats were categorised as of high (HC) or low (LC) positive affectivity based on their 50-kHz USV response to imitation of rough-and-tumble play ('tickling'). As adults, the rats were subjected to four weeks of CVS, after which D-amphetamine was administered in five daily doses followed by a challenge dose (all 1mg/kg IP) nine days later. CVS reduced sucrose preference in LC-rats only. After CVS, amphetamine-elicited 50-kHz USVs were significantly reduced in LC-rats, the effect of stress in HC-rats being smaller and less consistent. In previously stressed and amphetamine-treated LC-rats, locomotor response to amphetamine was attenuated. In stressed LC-rats, DOPAC levels and dopamine turnover were increased in striatum after amphetamine treatment, and dopamine D1 receptor levels were upregulated in nucleus accumbens. LC-rats had lower isoleucine levels in frontal cortex. These results show that stress-related changes in response to amphetamine are dependent on inter-individual differences in positive affectivity both at neurochemical and behavioural levels, and further support the notion of higher vulnerability of animals with low positive affect. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  1. Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: Evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys.

    Science.gov (United States)

    Banks, Matthew L; Snyder, Rodney W; Fennell, Timothy R; Negus, S Stevens

    2017-05-01

    Benzphetamine is a Schedule III anorectic agent that is a prodrug for d-amphetamine and d-methamphetamine and may have utility as an "agonist" medication for cocaine use disorder treatment. This study evaluated the pharmacokinetic-pharmacodynamic profile of benzphetamine using a drug discrimination procedure in rhesus monkeys. The potency and time course of cocaine-like discriminative stimulus effects were compared for benzphetamine (10-18mg/kg, intramuscular (IM)) and d-amphetamine (0.032-0.32mg/kg, IM) in monkeys (n=3-4) trained to discriminate IM cocaine (0.32mg/kg) from saline in a two-key food-reinforced discrimination procedure. Parallel pharmacokinetic studies in the same monkeys determined plasma benzphetamine, d-methamphetamine and/or d-amphetamine levels for correlation with behavioral effects. d-Amphetamine produced dose-dependent, time-dependent, and full cocaine-like effects, i.e. ≥90% cocaine-appropriate responding, in all monkeys without altering response rates. The time course of d-amphetamine's cocaine-like discriminative stimulus effects correlated with plasma d-amphetamine levels. Benzphetamine was 180-fold less potent than d-amphetamine and produced full cocaine-like effects in only 2 of 4 monkeys while significantly decreasing response rates. Benzphetamine administration increased plasma d-methamphetamine (peak at 100min) and d-amphetamine (peak at 24h) levels, but the time course of behavioral effects did not correlate with increased levels of benzphetamine, d-methamphetamine or d-amphetamine. These results suggest that benzphetamine yields d-amphetamine and d-methamphetamine as active metabolites in rhesus monkeys, but generation of these metabolites is not sufficient to account for benzphetamine behavioral effects. The incomplete cocaine substitution profile and protracted d-amphetamine plasma levels suggest that benzphetamine may still warrant further evaluation as a candidate pharmacotherapy for cocaine use disorder treatment. Copyright

  2. The pharmacology of amphetamine and methylphenidate: Relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities.

    Science.gov (United States)

    Faraone, Stephen V

    2018-04-01

    Psychostimulants, including amphetamines and methylphenidate, are first-line pharmacotherapies for individuals with attention-deficit/hyperactivity disorder (ADHD). This review aims to educate physicians regarding differences in pharmacology and mechanisms of action between amphetamine and methylphenidate, thus enhancing physician understanding of psychostimulants and their use in managing individuals with ADHD who may have comorbid psychiatric conditions. A systematic literature review of PubMed was conducted in April 2017, focusing on cellular- and brain system-level effects of amphetamine and methylphenidate. The primary pharmacologic effect of both amphetamine and methylphenidate is to increase central dopamine and norepinephrine activity, which impacts executive and attentional function. Amphetamine actions include dopamine and norepinephrine transporter inhibition, vesicular monoamine transporter 2 (VMAT-2) inhibition, and monoamine oxidase activity inhibition. Methylphenidate actions include dopamine and norepinephrine transporter inhibition, agonist activity at the serotonin type 1A receptor, and redistribution of the VMAT-2. There is also evidence for interactions with glutamate and opioid systems. Clinical implications of these actions in individuals with ADHD with comorbid depression, anxiety, substance use disorder, and sleep disturbances are discussed. Copyright © 2018 The Author. Published by Elsevier Ltd.. All rights reserved.

  3. 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.

  4. Serotonin (5-HT) precursor loading with 5-hydroxy-l-tryptophan (5-HTP) reduces locomotor activation produced by (+)-amphetamine in the rat.

    Science.gov (United States)

    Baumann, Michael H; Williams, Zakia; Zolkowska, Dorota; Rothman, Richard B

    2011-04-01

    Evidence suggests that increases in synaptic serotonin (5-HT) can reduce the stimulant properties of amphetamine-type drugs. Here we tested the hypothesis that administration of the 5-HT precursor 5-hydroxy-l-tryptophan (5-HTP), along with the peripheral decarboxylase inhibitor benserazide, would decrease locomotor effects of (+)-amphetamine. Drug treatments were administered to conscious male rats undergoing in vivo microdialysis in nucleus accumbens. During dialysis sampling, rats were housed in chambers equipped with photobeams to detect forward locomotion (i.e., ambulation) and repetitive movements (i.e., stereotypy). Extracellular concentrations of dopamine (DA) and 5-HT were measured by high-pressure liquid chromatography with electrochemical detection. 5-HTP (10 & 30 mg/kg, i.p.) plus benserazide (30 mg/kg, i.p.) caused dose-related increases in 5-HT but failed to alter other parameters. (+)-Amphetamine (0.3 & 1.0 mg/kg, i.p.) produced dose-related increases in DA, ambulation and stereotypy. Combined administration of 5-HTP and (+)-amphetamine evoked large elevations in extracellular DA and 5-HT, but caused significantly less ambulation than (+)-amphetamine alone (~50% reduction). Our results confirm that 5-HTP can decrease hyperactivity produced by (+)-amphetamine, even in the presence of elevations in dialysate DA. The data suggest that 5-HTP and (+)-amphetamine may be useful to broadly enhance monoamine function in the clinical setting, while reducing undesirable effects of (+)-amphetamine. Published by Elsevier Ireland Ltd.

  5. 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...

  6. Interactions of [3H]amphetamine with rat brain synaptosomes. I. Saturable sequestration

    International Nuclear Information System (INIS)

    Zaczek, R.; Culp, S.; Goldberg, H.; Mccann, D.J.; De Souza, E.B.

    1991-01-01

    Previous studies have identified a saturable site of d-[ 3 H]amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37 degree C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. (Abstract Truncated)

  7. 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 <13% and control samples made from authentic hair demonstrated an imprecision <26%. The method was applied to samples from a controlled study of amphetamine intake as well as 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. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. I. Saturable sequestration

    Energy Technology Data Exchange (ETDEWEB)

    Zaczek, R.; Culp, S.; Goldberg, H.; Mccann, D.J.; De Souza, E.B. (Addiction Research Center, Baltimore, MD (USA))

    1991-05-01

    Previous studies have identified a saturable site of d-({sup 3}H)amphetamine sequestration (AMSEQ) in rat brain synaptosomes. The present study characterized AMSEQ with respect to its subcellular, neuronal and regional distributions, ontogenetic development, pharmacological specificity and factors required for its maintenance. Although AMSEQ was reduced when assays were performed in Krebs' buffer incubated at 37{degree}C as compared to assays performed in isotonic Tris-sucrose buffer incubated at room temperature, the pharmacological profiles of AMSEQ were virtually identical under both conditions. AMSEQ was negligible in tissues outside the central nervous system, enriched in synaptosomes and partially reduced by striatal kainic acid lesion, indicating neuronal localization. The distribution of AMSEQ in the central nervous system was heterogenous. Highest levels were present in hypothalamus with progressively lower levels noted in parietal cortex, frontal cortex, striatum, thalamus, hippocampus, midbrain, cerebellum, pons-medulla and spinal cord. With regard to its ontogeny, AMSEQ increased early in neonatal life, reaching adult levels by postnatal day 14. Although the effects of amphetamine to abolish the transynaptosomal pH gradient suggest a possible role for this gradient in the maintenance of AMSEQ, the pharmacological profile of AMSEQ indicates that other factors are involved. An interaction with an intrasynaptosomal acid, such as N-acetylaspartate, may account for AMSEQ maintenance. AMSEQ did not possess a stereospecific preference for either d-(IC50 = 177 microM) or I-amphetamine (IC50 = 173 microM). However, the pharmacological profile of AMSEQ indicated structural specificity with antidepressants being relatively potent inhibitors. (Abstract Truncated)

  9. Cerebral radionuclide tomography using 123I-isopropyl-amphetamine in cerebral ischaemic pathology

    International Nuclear Information System (INIS)

    Cesaro, P.; Moretti, J.L.; Caron, J.P.; Roualdes, B.; Louarn, F.; N'Guyen, J.P.; Gaston, A.; Degos, J.D.

    1985-01-01

    Thirty patients with previous cerebral ischaemic accident were explored by both computerized tomography (CT) and radionuclide tomography after injection of 123 I-labeled N-isopropyl-iodo-amphetamine. All lesions that were visible at CT were also visible at radionuclide tomography. However, in 7 patients with normal CT results the latter method showed areas of cerebral activity anatomically correlated with neurological signs or vascular lesions. Cerebellar diaschisis was observed in 50% of established lesions in the carotid territory. Radionuclide tomography therefore appears as a very sensitive method to be used in ischaemic pathology with transient or regressive accidents [fr

  10. Brain lipidomic changes after morphine, cocaine and amphetamine administration - DESI - MS imaging study.

    Science.gov (United States)

    Bodzon-Kulakowska, Anna; Antolak, Anna; Drabik, Anna; Marszalek-Grabska, Marta; Kotlińska, Jolanta; Suder, Piotr

    2017-07-01

    Drug addiction is a complex disorder, evoking significant changes in the proteome of the central nervous system. To check if there are also changes in the lipidomic profiles we used desorption electrospray-MS technique for imaging of the brain slices of rats exposed to morphine, cocaine and amphetamine. Our investigations showed alternative regulation of selected lipid's levels in the central nervous system structures, under the influence of applied drugs. Results of our investigations can show changes in the brain treated with drugs of abuse in the new light, indicating role of the lipids in the addiction development. Copyright © 2017. Published by Elsevier B.V.

  11. 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.

  12. Cerebral radionuclide tomography using /sup 123/I-isopropyl-amphetamine in cerebral ischaemic pathology

    Energy Technology Data Exchange (ETDEWEB)

    Cesaro, P.; Moretti, J.L.; Caron, J.P.; Roualdes, B.; Louarn, F.; N' Guyen, J.P.; Gaston, A.; Degos, J.D. (C.H.U. Henri Mondor, Dept. de Neurosciences Medicales, 94 - Creteil (France))

    1985-02-02

    Thirty patients with previous cerebral ischaemic accident were explored by both computerized tomography (CT) and radionuclide tomography after injection of /sup 123/I-labeled N-isopropyl-iodo-amphetamine. All lesions that were visible at CT were also visible at radionuclide tomography. However, in 7 patients with normal CT results the latter method showed areas of cerebral activity anatomically correlated with neurological signs or vascular lesions. Cerebellar diaschisis was observed in 50% of established lesions in the carotid territory. Radionuclide tomography therefore appears as a very sensitive method to be used in ischaemic pathology with transient or regressive accidents.

  13. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

    OpenAIRE

    Romana Šlamberová; Eva Macúchová; Kateryna Nohejlová; Andrea Štofková; Jana Jurčovičová

    2014-01-01

    The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA) exposure to adult amphetamine (AMP) treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg) or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed) were administered with AMP (5 mg/kg) or saline (1 ml/kg) in adulthood. Behaviour in unknown environment was examined in open field test (Laboras), activ...

  14. Cannabinoid CB1 Receptor Activation Mediates the Opposing Effects of Amphetamine on Impulsive Action and Impulsive Choice

    Science.gov (United States)

    Wiskerke, Joost; Stoop, Nicky; Schetters, Dustin; Schoffelmeer, Anton N. M.; Pattij, Tommy

    2011-01-01

    It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior. PMID:22016780

  15. 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......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...

  16. Brain SPECT with /sup 123/I-labelled amphetamine derivatives in epilepsy and migraine

    International Nuclear Information System (INIS)

    Biersack, H.J.; Froscher, W.; Penin, H.; Bulau, P.; Reichmann, K.; Winkler, C.

    1986-01-01

    On the basis of positron tomography (PET) results it has been well established that seizures are connected with increases in regional cerebral blood flow and metabolism. In the interictal stage, however, regionally diminished perfusion can be observed in the affected cortical areas. As changes in cerebral function due to seizures are seldom accompanied by structural changes they often cannot be detected by radiographic techniques. Here the EEG is useful, but has significant limitations: It is often difficult to lateralize or localize the origin of the seizure or to assess the severity and extent of underlying cerebral involvement. Since 1982 SPECT with /sup 123/I-labelled N-isopropyl amphetamines (IMP) has been used for the evaluation of epilepsy. By means of this technique, identical findings - ictally increased, interictally decreased tracer accumulation - as with PET were established. In addition, amphetamine SPECT can reveal increased perfusion in epileptic foci at a time when there is focal electrical discharge, even in the absence of clinically recognizable seizures. The present paper presents an overview of the authors' results in a relatively large series of patients with epilepsy. Data are also included of patients with migraine accompagnee - a disease in which EEG pathology may also be observed

  17. Cocaine versus food choice procedure in rats: environmental manipulations and effects of amphetamine.

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C; Negus, S Stevens; Caine, S Barak

    2013-03-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0-1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. © Society for the Experimental Analysis of Behavior.

  18. Self-monitoring cognitive performance during sleep deprivation: effects of modafinil, d-amphetamine and placebo.

    Science.gov (United States)

    Baranski, J V; Pigeau, R A

    1997-06-01

    Self-monitoring refers to the ability to assess accurately one's own performance in a specific environment. The present study investigated the effects of the stimulating drugs modafinil (300 mg) and d-amphetamine (20 mg) on the ability to self-monitor cognitive performance during 64 h of sleep deprivation (SD) and sustained mental work. Two cognitive tasks were investigated: a visual (perceptual) judgement task and a complex mental addition task. Subjects in the placebo condition displayed marked circadian and SD effects on cognitive task performance but their self-monitoring was substantively undisturbed by SD. Subjects performing under the influence of d-amphetamine likewise displayed highly proficient self-monitoring throughout the SD period. In contrast, modafinil had a disruptive effect on self-monitoring, inducing a reliable 'overconfidence' effect (i.e. an overestimation of actual cognitive performance), which was particularly marked 2-4 h post-dose. Although modafinil has proven to be a safe and effective countermeasure to the effects of extensive SD on cognitive task performance, we encourage a more comprehensive understanding of the relation between its subjective and performance enhancing effects before the drug is recommended as a viable fatigue countermeasure.

  19. [Determination of amphetamine and methamphetamine in human hair using gas chromatography/mass spectrometry].

    Science.gov (United States)

    Láznicková, J; Dĕdicová, M; Vorel, F

    2000-05-01

    The authors present a procedure of concurrent identification and quantification of amphetamine and metamphetamine in human hair. The method involves rinsing of the hair (distilled water 55 degrees C, 0.1 M hydrochloric acid, distilled water to neutral reaction, methanol) drying in air, homogenization by cutting (1-2 mm long), alkaline hydrolysis (20 mg hair, 1 ml 1 M sodium hydroxide, 55 degrees C, 120 min.), neutralization with 1 M hydrochloric acid to pH = 7, extracting benzoylation with 2,3,4,5,6-pentafluorobenzoyl chloride (0.3 ml 1 M sodium hydroxide, 4 ml cyclohexane, 30 ul cyclohexylamine in cyclohexane of a concentration of 20 ng/ul--internal standard, 50 ul aqueous solution of triethylamine hydrochloride concentration of 100 mg/ml--reaction catalyst and 10 ul of derivation agent 2,3,4,5,6-pentafluorobenzoyl chloride dilution 1:10, shaking for 5 mins. by hand and leaving to stand for 10 mins.), centrifugation (5 mins., 3000 rotations/min.), collection of 2 ml cyclohexane layer, its evaporation at 40 degrees C in nitrogen atmosphere and dilution with 100 ul cyclohexane. The derivated extract was subjected to analysis by the GC-MS method. The procedure was used for segmentation analysis of hair of two subjects abusing metamphetamine for prolonged periods. The revealed concentrations varied within the range of 0.99-5.25 mg/kg metamphetamine and 0.13-0.73 mg/kg amphetamine.

  20. 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.

  1. Which amphetamine-type stimulants can be detected by oral fluid immunoassays?

    Science.gov (United States)

    Souza, Daniele Z; Boehl, Paula O; Comiran, Eloisa; Prusch, Débora S; Zancanaro, Ivomar; Fuentefria, Alexandre M; Pechansky, Flavio; Duarte, Paulina C A V; De Boni, Raquel B; Fröehlich, Pedro E; Limberger, Renata P

    2012-02-01

    The use of oral fluid for monitoring drug consumption on roads has many advantages over conventional biological fluids; therefore, several immunoassays have been developed for this purpose. In this work, the ability of 3 commercial immunoassays to detect amphetamine-type stimulants (ATSs) in oral fluid was assessed. In addition, it was reviewed the main controlled ATSs available worldwide, as well as the oral fluid immunological screening tests that have been used for identifying ATSs in drivers. The analytical specificity of amphetamine direct enzyme-linked immunosorbent assay (ELISA), methamphetamine direct ELISA (Immunalysis Corporation), and Oral-View saliva multidrug of abuse test (Alfa Scientific Designs) was evaluated using ATS-spiked oral fluid. Legislation and published articles that report the use of immunological screening tests to detect ATS consumption in conductors were reviewed, including the kit's technical information, project reports, police and drug databases. Even at high concentrations, the tested assays were not able to detect methylphenidate, fenproporex, or diethylpropion, controlled ATSs legally marketed in many countries. This evidences the need to develop new kits that enable one to control the misuse of prescription ATSs on roads through oral fluid immunoassays.

  2. Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

    Science.gov (United States)

    Nazarali, A J; Baker, G B; Coutts, R T; Pasutto, F M

    1983-01-01

    Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

  3. Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use.

    Science.gov (United States)

    Poklis, A; Moore, K A

    1995-02-01

    The cross-reactivity of l-methamphetamine (l-desoxyephedrine) to the EMIT-d.a.u. class (EC) and EMIT-d.a.u. monoclonal amphetamine/methamphetamine (EM) assays was evaluated in urine specimens collected from six subjects using Vicks inhalers. The subjects were five men and a woman ranging from 27 to 47 years old. Four subjects used the inhaler as recommended by the manufacturer for five consecutive days; two subjects used double this dosage for three consecutive days. All urine voids were collected, totaling 132 specimens. All specimens were analyzed by the EC and EM assays. Specimens yielding a positive response were then analyzed by chiral and achiral gas chromatography/mass spectrometry (GC/MS). No specimen was positive by the EM assay, whereas 17 specimens yielded positive EC results. One subject for form the "as recommended" group had six positive specimens with maximum l-desoxyephedrine of 872 ng/ml. Both subjects using twice the recommended dosage had positive specimens, maximum l-desoxyephedrine of 1,560 ng/ml. No positive specimen contained > 200 ng/ml l-amphetamine.

  4. Cocaine Versus Food Choice Procedure in Rats: Environmental Manipulations and Effects of Amphetamine

    Science.gov (United States)

    Thomsen, Morgane; Barrett, Andrew C.; Negus, S. Stevens; Caine, S. Barak

    2014-01-01

    We have adapted a nonhuman primate model of cocaine versus food choice to the rat species. To evaluate the procedure, we tested cocaine versus food choice under a variety of environmental manipulations as well as pharmacological pretreatments. Complete cocaine-choice dose-effect curves (0–1.0 mg/kg/infusion) were obtained for each condition under concurrent fixed ratio schedules of reinforcement. Percentage of responding emitted on the cocaine-reinforced lever was not affected significantly by removal of cocaine-associated visual or auditory cues, but it was decreased after removal of response-contingent or response-independent cocaine infusions. Cocaine choice was sensitive to the magnitude and fixed ratio requirement of both the cocaine and food reinforcers. We also tested the effects of acute (0.32, 0.56, 1.0, 1.8 mg/kg) and chronic (0.1, 0.32 mg/kg/hr) d-amphetamine treatment on cocaine choice. Acute and chronic d-amphetamine had opposite effects, with acute increasing and chronic decreasing cocaine choice, similar to observations in humans and in nonhuman primates. The results suggest feasibility and utility of the choice procedure in rats and support its comparability to similar procedures used in humans and monkeys. PMID:23319458

  5. Matrix effect and cross-reactivity of select amphetamine-type substances, designer analogues, and putrefactive amines using the Bio-Quant direct ELISA presumptive assays for amphetamine and methamphetamine.

    Science.gov (United States)

    Apollonio, Luigino G; Whittall, Ian R; Pianca, Dennis J; Kyd, Jennelle M; Maher, William A

    2007-05-01

    The aim of this study was to evaluate the Bio-Quant Direct ELISA assays for amphetamine and methamphetamine in the routine presumptive screening of biological fluids. Standard concentration curves of the target analytes were assayed to assess sensitivity, and known concentrations of common amphetamine-type substances (ephedrine, pseudoephedrine, phentermine), designer analogues (MDA, MDMA, MDEA, MBDB, PMA, 4-MTA, 2CB), and putrefactive amines (phenylethylamine, putrescine, tryptamine, tyramine) were analyzed to determine cross-reactivity. Results of the standard curve studies show the capacity of both Direct ELISA kits to confidently detect down to 3 ng/mL interday (PBS matrix; CVs 6.3-15.5%). Cross-reactivity relative to that of 50 ng/mL preparations of the target compounds demonstrated that the Direct ELISA kit for amphetamine also detected MDA (282%), PMA (265%), 4-MTA (280%), and phentermine (61%), and the Direct ELISA for methamphetamine also assayed positive for MDMA (73%), MDEA (18%), pseudoephedrine (19%), MBDB (8%), and ephedrine (9%). Matrix studies demonstrated that both ELISA kits could be applied to screening of blood, urine, and saliva to a concentration of 6 ng/mL or lower. In conclusion, the Bio-Quant Direct ELISA kits for amphetamine and methamphetamine are fast and accurate and have demonstrated themselves to be useful tools in routine toxicological testing.

  6. 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

  7. Anorexic and behavioural effects of a new imidazo-isoindole derivative (mazindol) in comparison with d-amphetamine in the rat.

    Science.gov (United States)

    Babbini, M; Gaiardi, M; Bartoletti, M

    1977-01-01

    The effect of an imidazo-isoindole derivative (mazindol) upon motor and feeding activity and two different avoidance behaviours have been compared with those of d-amphetamine in rats. It was found that both drugs depress feeding activity in a dose-related manner and increase the motor activity of the animals. However, the ratio of the lowest motility-increasing dose and the lowest appetite suppressant dose is 0.5 for d-amphetamine and 2 for mazindol. Mazindol, like d-amphetamine, caused a stereotyped behaviour in rats when given in very high doses, but the range between the anorexic and the stereotyped behaviour dose is much higher for mazindol than for d-amphetamine. The shuttle-box avoidance behaviour suppressed by tetrabenazine is completely restored by d-amphetamine and partially by mazindol. Lever-pressing avoidance suppressed by tetrabenazine is restored by d-amphetamine while mazindol at the doses used is ineffective. It is concluded that mazindol could be an anorexic agent better suited than d-amphetamine for clinical use.

  8. Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core

    NARCIS (Netherlands)

    Nordquist, R.E.; Vanderschuren, L.J.M.J.; Jonker, A.J.; Bergsma, M.; de Vries, T.J.; Pennartz, C.M.A.; Voorn, P.

    2008-01-01

    Rationale: Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals

  9. Association of Cocaine- and Amphetamine-Regulated Transcript (CART) Messenger RNA Level, Food Intake, and Growth in Channel Catfish

    Science.gov (United States)

    Cocaine-and Amphetamine-Regulated Transcript (CART) is a potent hypothalamic anorectic peptide in mammals and fish. We hypothesized that increased food intake is associated with changes in expression of CART mRNA within the brain of channel catfish. Objectives were to clone the CART gene, examine ...

  10. 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...

  11. 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.

  12. 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

    to the distal C terminus of DAT and colocalized with DAT in dopaminergic neurons. CaMKIIalpha stimulated dopamine efflux via DAT in response to amphetamine in heterologous cells and in dopaminergic neurons. CaMKIIalpha phosphorylated serines in the distal N terminus of DAT in vitro, and mutation...

  13. 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.

  14. Long-Term Tolerability and Effectiveness of Once-Daily Mixed Amphetamine Salts (Adderall XR) in Children with ADHD

    Science.gov (United States)

    McGough, James J.; Biederman, Joseph; Wigal, Sharon B.; Lopez, Frank A.; McCracken, James T.; Spencer, Thomas; Zhang, Yuxin; Tulloch, Simon J.

    2005-01-01

    Objective: To evaluate the long-term tolerability and effectiveness of extended-release mixed amphetamine salts (MAS XR; Adderall XR[R]) in children with attention-deficit/hyperactivity disorder (ADHD). Method: This was a 24-month, multicenter, open-label extension of TWO placebo-controlled studies of MAS XR in children with ADHD aged 6 to 12…

  15. 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

    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...

  16. Effects of high amphetamine dose on mood and cerebral glucose metabolism in normal volunteers using positron emission tomography (PET)

    NARCIS (Netherlands)

    Vollenweider, FX; Maguire, RP; Leenders, KL; Mathys, K; Angst, J

    1998-01-01

    The effects of high euphorigenic doses of D-amphetamine (0.9-1.0 mg/kg p.o.) on regional cerebral glucose metabolism (rCMRglu) and psychological measures were investigated in 10 healthy human volunteers using a within-subject design and [F-18]-fluorodeoxygrucose positron emission tomography

  17. Amphetamine and Dopamine-Induced Immediate Early Gene Expression in Striatal Neurons Depends on Postsynaptic NMDA Receptors and Calcium

    Science.gov (United States)

    Konradi, Christine; Leveque, Jean-Christophe; Hyman, Steven E.

    2014-01-01

    Amphetamine and cocaine induce the expression of both immediate early genes (IEGs) and neuropeptide genes in rat striatum. Despite the demonstrated dependence of these effects on D1 dopamine receptors, which activate the cyclic AMP pathway, there are several reports that amphetamine and cocaine-induced IEG expression can be inhibited in striatum in vivo by NMDA receptor antagonists. We find that in vivo, the NMDA receptor antagonist MK-801 inhibits amphetamine induction of c-fos acutely and also prevents downregulation of IEG expression with chronic amphetamine administration. Such observations raise the question of whether dopamine/glutamate interactions occur at the level of corticostriatal and mesostriatal circuitry or within striatal neurons. Therefore, we studied dissociated striatal cultures in which midbrain and cortical presynaptic inputs are removed. In these cultures, we find that dopamine- or forskolin-mediated IEG induction requires Ca2+ entry via NMDA receptors but not via L-type Ca2+ channels. Moreover, blockade of NMDA receptors diminishes the ability of dopamine to induce phosphorylation of the cyclic AMP responsive element binding protein CREB. Although these results do not rule out a role for circuit-level dopamine/glutamate interactions, they demonstrate a requirement at the cellular level for interactions between the cyclic AMP and NMDA receptor pathways in dopamine-regulated gene expression in striatal neurons. PMID:8753884

  18. Acute effects of lisdexamfetamine and D-amphetamine on social cognition and cognitive performance in a placebo-controlled study in healthy subjects.

    Science.gov (United States)

    Dolder, Patrick C; Strajhar, Petra; Vizeli, Patrick; Odermatt, Alex; Liechti, Matthias E

    2018-02-09

    Amphetamines are used as medications but are also misused as cognitive enhancers by healthy subjects and may have additional effects on social cognition. We investigated the acute effects of single, high, equimolar doses of D-amphetamine (40 mg) and lisdexamfetamine (100 mg) on social cognition and cognitive performance using a randomized, placebo-controlled, double-blind, cross-over design in 24 healthy volunteers. Effects on social cognition were assessed using the Facial Emotion Recognition Task (FERT), Multifaceted Empathy Test (MET), and Sexual Arousal Task (SAT). Cognitive performance was measured using the Digit Symbol Substitution Test (DSST), Digit Span (DS), Stop-Signal Task (SST), and Mackworth Clock Test (MCT). D-Amphetamine and lisdexamfetamine had small effects on measures of social cognition. There were no effects on emotion recognition on the FERT. D-Amphetamine increased direct empathy on the MET, but only for positive stimuli. Both amphetamines increased ratings of pleasantness and attractiveness on the SAT in response to sexual but also to neutral stimuli. D-Amphetamine and lisdexamfetamine increased cognitive performance (go-accuracy and vigilance on the SST and MCT, respectively). Lisdexamfetamine increased processing speed on the DSST. Neither drug had an effect on the DS. Single, high, equimolar doses of D-amphetamine and lisdexamfetamine enhanced certain aspects of cognitive performance in healthy non-sleep-deprived subjects. Both amphetamines also slightly altered aspects of social cognition. Whether these small effects also influence social interaction behavior in amphetamine users remains to be investigated. The study was registered at ClinicalTrials.gov (NCT02668926).

  19. 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.

  20. Different oxidative profile and nicotinic receptor interaction of amphetamine and 3,4-methylenedioxy-methamphetamine.

    Science.gov (United States)

    Chipana, C; García-Ratés, S; Camarasa, J; Pubill, D; Escubedo, E

    2008-02-01

    d-Amphetamine (AMPH) and MDMA increased intracellular production of reactive oxygen species (ROS) in isolated mouse striatal synaptosomes. MDMA showed a maximal oxidative effect at 50-100 microM. However, for AMPH a double maximum was obtained, the first between 0.1 and 1 microM and the second at 1mM. No oxidative effect was present in synaptosomes from reserpinized mice. Cocaine and l-deprenyl inhibited MDMA and AMPH (0.1 microM) ROS production but not that of AMPH at a higher concentration (1mM). When this high concentration was used, its oxidative effect was abolished by a phospholipase A(2) inhibitor. Delta(9)-Tetrahydrocannabinol fully prevented the oxidative effect of AMPH and MDMA, by a CB(1) receptor-independent mechanism, as did it NPC 15437 and genistein. The pro-oxidative effect induced by AMPH and MDMA showed a strong dependence on calcium (extracellular and from internal stores) and also was inhibited by nicotinic receptor (nAChR) antagonists dihydro-beta-erythroidine, methyllycaconitine (MLA) and alpha-bungarotoxin. MDMA displaced [(3)H]epibatidine and [(3)H]MLA binding with higher affinity than AMPH. Both amphetamines competitively displaced [(3)H]epibatidine from heteromeric receptors but results obtained from [(3)H]MLA binding demonstrated a non-competitive profile. Preincubation of PC12 cells with AMPH or MDMA reduced [(3)H]dopamine uptake. For MDMA, this effect was prevented by MLA. To summarize, comparing AMPH and MDMA we have demonstrated that these drugs induce an oxidative effect dependent on drug concentration and also reduce dopamine uptake. Processes that are known to affect dopamine transporter functionality also seem to modulate amphetamine derivatives-induced ROS production. For MDMA, acute effects tested are blocked by nAChR antagonists, which points to the possibility that these antagonists could be used to treat some of the adverse effects described in MDMA abusers. Conversely, no implication of nicotinic receptors has been proved

  1. Comparison of radioimmunoassay and gas chromatographic mass spectrometric assay for d-amphetamine

    International Nuclear Information System (INIS)

    Powers, K.H.; Ebert, M.H.

    1979-01-01

    Quantification of low levels of psychotropic drugs (10 -7 to 10 -9 g ml -1 ) in small volumes of plasma requires sensitive and accurate methods. Validation of these methods is best achieved by comparing results obtained using several techniques. In this study, amphetamine levels in plasma were measured using gas chromatography mass spectrometry and radioimmunoassay. Correlation of the results obtained by the two methods was found to be positive and high (R = 0.9822). The average coefficient of variation between assays for gas chromatography mass spectrometry was 5.8% and for radioimmunoassay was 12.3%, while the average coefficient of variation within assays for gas chromatography mass spectrometry was 4.9% and for radioimmunoassay 6.9%. Although gas chromatography mass spectrometry was 1.9 times more sensitive than radioimmunoassay, for most purposes, the convenience of the radioimmunoassay method outweighs the technical superiority of gas chromatography mass spectrometry. (author)

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

    International Nuclear Information System (INIS)

    He Yi; Vargas, Angelica; Kang, Youn-Jung

    2007-01-01

    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 3 PO 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 μg L -1 , repeatability of the extraction (R.S.D. -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

  3. Contribution of the dorsal noradrenergic bundle to the effect of amphetamine on acetylcholine turnover

    International Nuclear Information System (INIS)

    Robinson, S.E.

    1986-01-01

    In order to determine the contribution of the noradrenergic projections of the locus coeruleus to the action of amphetamine on cholinergic neurons in several areas of the brain, the dorsal noradrenergic bundle was selectively lesioned by injection of the neurotoxin 6-hydroxydopamine. The bundles of Equithesin-anesthetized male rats were lesioned bilaterally by stereotaxically-placed injections of 6-OHDA. The animals were killed in the microwave and constant rate infusion with phosphoryl ( 2 H 9 )-choline was begun. Levels of ACh and choline and TR /SUB ACh/ were determined by a mass fragmentographic technique. Rats not exhibiting the proper decrease in NE were excluded from all data calculations. It is shown that noradrenergic neurons travelling in the dorsal noradrenergic bundle do not exert a tonic action on cholinergic neurons in the cortex, hippocampus or hypothalamus

  4. 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.

  5. Prenatal tetrahydrocannabinol (THC) alters cognitive function and amphetamine response from weaning to adulthood in the rat.

    Science.gov (United States)

    Silva, Lindsay; Zhao, Ning; Popp, Susanna; Dow-Edwards, Diana

    2012-01-01

    Research suggests that not only is marijuana use prevalent among women of reproductive age, but a significant number of women continue to use marijuana and its derivatives throughout pregnancy. Many studies have shown, in both humans and animals, that marijuana exposure during adolescence and adulthood is detrimental to normal cognition and memory. In this study, we examined the effects of daily intravenous injections of 0.15 mg/kg Δ(9)-tetrahydrocannabinol (THC), given to pregnant dams throughout gestation, on cognitive function in the offspring. Offspring were exposed to three tests: a passive avoidance test at postnatal day (PND) 22, an active place avoidance test at PND 45, and an attention task at PND 60, which assessed learning and long-term memory, spatial working memory and prediction, and attention, respectively. Other offspring were also given a 1mg/kg amphetamine challenge at PND 60. Passive avoidance testing showed that prenatal THC had no effect on acquisition but interfered with consolidation during retention testing. The active place avoidance task showed no treatment-related effects on acquisition but a significant treatment effect was observed in reversal performance in males. The attention task showed that a smaller percentage of THC-exposed rats completed the test, although the failure rate of both groups was quite high. Finally, THC exposed animals, both male and female, showed a dampened locomotor response to amphetamine, but females were more active than males overall. These results suggest that prenatal THC exposure has effects on certain aspects of cognitive function in rats from weaning to adulthood. These effects suggest that prenatal marijuana exposure could also alter cognitive function in humans and therefore have an impact on school performance and dampen responses to psychostimulants as well. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Differential effects of psychomotor stimulants on attentional performance in rats: nicotine, amphetamine, caffeine and methylphenidate.

    Science.gov (United States)

    Bizarro, L; Patel, S; Murtagh, C; Stolerman, I P

    2004-05-01

    Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.

  7. Memantine protects against amphetamine derivatives-induced neurotoxic damage in rodents.

    Science.gov (United States)

    Chipana, C; Torres, I; Camarasa, J; Pubill, D; Escubedo, E

    2008-06-01

    We hypothesize that 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) interact with alpha-7 nicotinic receptors (nAChR). Here we examine whether memantine (MEM), an antagonist of NMDAR and alpha-7 nAChR, prevents MDMA and METH neurotoxicity. MEM prevented both serotonergic injury induced by MDMA in rat and dopaminergic lesion by METH in mice. MEM has a better protective effect in front of MDMA- and METH-induced neurotoxicity than methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist. The double antagonism that MEM exerts on NMDA receptor and on alpha-7 nAChR, probably contributes to its effectiveness. MEM inhibited reactive oxygen species production induced by MDMA or METH in synaptosomes. This effect was not modified by NMDA receptor antagonists, but reversed by alpha-7 nAChR agonist (PNU 282987), demonstrating a preventive effect of MEM as a result of it blocking alpha-7 nAChR. In synaptosomes, MDMA decreased 5-HT uptake by about 40%. This decrease was prevented by MEM and by MLA but enhanced by PNU 282987. A similar pattern was observed when we measured the dopamine transport inhibited by METH. The inhibition of both transporters by amphetamine derivatives seems to be regulated by the calcium incorporation after activation of alpha-7 nAChR. MDMA competitively displaces [(3)H]MLA from rat brain membranes. MEM and METH also displace [(3)H]MLA with non-competitive displacement profiles that fit a two-site model. We conclude that MEM prevents MDMA and METH effects in rodents. MEM may offer neuroprotection against neurotoxicity induced by MDMA and METH by preventing the deleterious effects of these amphetamine derivatives on their respective transporters.

  8. 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. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Bioanalysis for cocaine, opiates, methadone, and amphetamines exposure detection during pregnancy.

    Science.gov (United States)

    Concheiro, Marta; Lendoiro, Elena; de Castro, Ana; Gónzalez-Colmenero, Eva; Concheiro-Guisan, Ana; Peñas-Silva, Patricia; Macias-Cortiña, Manuel; Cruz-Landeira, Angelines; López-Rivadulla, Manuel

    2017-06-01

    Drug exposure during pregnancy constitutes a major legal issue and a public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta, and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography-tandem mass spectrometry for the determination of cocaine, opioids, methadone, and amphetamines, and compared the analytical results from the four different matrices. The cases were divided in non-exposure, low, and frequent exposure, based on maternal hair concentrations and segmental analysis by trimesters. For cocaine, 62 cases tested positive in hair, 9 in meconium, 6 in placenta and 7 in umbilical cord. In the case of opioids, 14 maternal hair cases were positive, 11 meconium and umbilical cord and 9 placenta samples. For methadone, 11 cases were positive in hair, 9 in meconium and 6 in placenta and umbilical cord. For amphetamines, 18 cases were positive according to maternal hair, but all meconium, placenta, and umbilical cord tested negative. Maternal hair was the most sensitive specimen to detect drug exposure during pregnancy. Meconium, placenta, and umbilical cord tested positive if hair concentrations showed frequent drug use during the whole pregnancy, especially during the third trimester. Meconium, placenta, and umbilical cord also tested positive for morphine and metabolites, if this drug was administered during labour and delivery. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  10. Discriminative stimulus effects of cocaine and amphetamine in rats following developmental exposure to polychlorinated biphenyls (PCBs)

    Science.gov (United States)

    Sable, Helen J. K.; Monaikul, Supida; Poon, Emily; Eubig, Paul A.; Schantz, Susan L.

    2010-01-01

    Polychlorinated biphenyls (PCBs) are environmental neurotoxicants known to affect the brain dopaminergic (DA) system. This project investigated whether developmental exposure to PCBs would alter the discriminative stimulus effects of psychostimulant drugs known to act on the DA system. Female Long-Evans rats were orally exposed to 0, 3, or 6 mg/kg/day of an environmentally relevant PCB mixture from four weeks prior to breeding through weaning of their litters on PND 21. When they reached adulthood one male and female/litter were trained to discriminate cocaine (10.0 mg/kg, IP) from saline by repeatedly pairing cocaine injections with reinforcement on one operant response lever, and saline injections with reinforcement on the other lever. After response training, generalization tests to four lower doses of cocaine (7.5, 5.0, 2.5, and 1.25 mg/kg, IP) and to amphetamine (1.0, 0.5, 0.25, and 0.125 mg/kg, IP) were given two days/week, with additional training dose days in-between. Percent responding of the PCB-exposed rats on the cocaine-paired lever was significantly higher than that of controls for the highest generalization dose of cocaine, and lower than that of controls for the highest dose of amphetamine. Response rate and percent responding on the cocaine lever did not differ among the exposure groups on the days when the training dose of cocaine was given, suggesting the generalization test results were not due to pre-existing differences in discrimination ability or rate of responding. These findings suggest developmental PCB exposure can alter the interoceptive cues of psychostimulants. PMID:20933596

  11. The influence of social structure on social isolation in amphetamine-treated Java monkeys (Macaca fascicularis).

    Science.gov (United States)

    Knobbout, D.A.; Ellenbroek, B.A.; Cools, A.R.

    1996-10-01

    Amphetamine-induced social isolation in monkeys has often been considered a valid animal model for certain negative symptoms of schizophrenia. However, there appear to be many ambiguities in relation to the exact nature of the isolation. Therefore, the effect of orally administered amphetamine (AMP) on the occurrence of social isolation in Java monkeys was studied. In part I the rank dependency of the effects of AMP (0.5mg/kg) was investigated in four alpha-males and three beta-males. AMP increased 'proximity' and 'passive groom', and decreased 'active allogroom' in alpha-males. In contrast, AMP decreased all three behavioural elements to a certain extent in beta-males. It is concluded that AMP induces social isolation in beta-males, but not in alpha-males. In part II of this study the AMP-induced behaviour of the treated monkey and the simultaneously occurring changes in the non-treated monkeys were investigated in a detailed study of a single social group. AMP significantly reduced the frequency of 'exploration', 'locomotion', 'self-groom', 'swing', 'active groom', 'inspect', 'approach' and originally-present stereotypies. Thus AMP apparently reduces the ability to initiate behaviour which is characteristic for the adult animal. AMP did not affect the frequency of 'present' and 'play' and enhanced that of 'aggression' and 'fear' in the beta-male; it also elicited various juvenile-like behaviours in both alpha- and beta-males, suggesting that AMP induces a behavioural regression. Furthermore, the behaviour of the non-treated monkeys of the group was decisive for the occurrence of social isolation of the treated monkey. Thus, the effects of AMP on the social behaviour of Java monkeys depend on the individual sensitivity, the social position which the subject occupies in its group, and the behaviour of the partners of the treated subject.

  12. Distinctive effects of modafinil and d-amphetamine on the homeostatic and circadian modulation of the human waking EEG.

    Science.gov (United States)

    Chapotot, Florian; Pigeau, Ross; Canini, Frédéric; Bourdon, Lionel; Buguet, Alain

    2003-03-01

    Modafinil is a wake-promoting agent that affects hypothalamic structures involved in the homeostatic and circadian regulation of vigilance. Administered during sleep deprivation, it reduces the need for prolonged recovery sleep and decreases the rebound in EEG slow-wave activity. These diachronic effects suggest an action of modafinil on a homeostatic sleep regulatory process. The aim of this study was to determine whether modafinil, in comparison to the d-amphetamine reference psychostimulant and to placebo, interferes with the vigilance regulatory processes reflected in the EEG during waking. Thirty-three healthy subjects were investigated during 60 h of sustained wakefulness in a double-blind placebo-controlled parallel-design study. A 4-min maintenance-of-wakefulness test administered hourly allowed the concomitant assessment of alertness and waking EEG activity. The effects of equipotent psychostimulant dosages (modafinil 300 mg and d-amphetamine 20 mg) were evaluated at the beginning of the first sleep deprivation night, at the end of the second sleep deprivation night and in the afternoon preceding the first recovery night. One hour following ingestion, both psychostimulants increased alertness during 10-12 h, independently of the time of administration. At the level of the waking EEG, d-amphetamine attenuated the natural circadian rhythm of the different frequency bands and suppressed the sleep deprivation-related increase in low frequency (0.5-7 Hz) powers. In contrast, modafinil, which exhibited a transient amphetamine-like effect, had slight effect on circadian rhythms. Its selective action was characterized by maintenance of the alpha(1) (8.5-11.5 Hz) EEG power, which under placebo exhibited a homeostatic decrease paralleling that of alertness with a circadian trough at night. These findings demonstrate that the alertness-promoting effects of modafinil and d-amphetamine involve distinct EEG activities and do not reside on the same vigilance regulatory

  13. Fenproporex N-dealkylation to amphetamine--enantioselective in vitro studies in human liver microsomes as well as enantioselective in vivo studies in Wistar and Dark Agouti rats.

    Science.gov (United States)

    Kraemer, Thomas; Pflugmann, Thomas; Bossmann, Michael; Kneller, Nicole M; Peters, Frank T; Paul, Liane D; Springer, Dietmar; Staack, Roland F; Maurer, Hans H

    2004-09-01

    Fenproporex (FP) is known to be N-dealkylated to R(-)-amphetamine (AM) and S(+)-amphetamine. Involvement of the polymorphic cytochrome P450 (CYP) isoform CYP2D6 in metabolism of such amphetamine precursors is discussed controversially in literature. In this study, the human hepatic CYPs involved in FP dealkylation were identified using recombinant CYPs and human liver microsomes (HLM). These studies revealed that not only CYP2D6 but also CYP1A2, CYP2B6 and CYP3A4 catalyzed this metabolic reaction for both enantiomers with slight preference for the S(+)-enantiomer. Formation of amphetamine was not significantly changed by quinidine and was not different in poor metabolizer HLM compared to pooled HLM. As in vivo experiments, blood levels of R(-)-amphetamine and S(+)-amphetamine formed after administration of FP were determined in female Dark Agouti rats (fDA), a model of the human CYP2D6 poor metabolizer phenotype (PM), male Dark Agouti rats (mDA), an intermediate model, and in male Wistar rats (WI), a model of the human CYP2D6 extensive metabolizer phenotype. Analysis of the plasma samples showed that fDA exhibited significantly higher plasma levels of both amphetamine enantiomers compared to those of WI. Corresponding plasma levels in mDA were between those in fDA and WI. Furthermore, pretreatment of WI with the CYP2D inhibitor quinine resulted in significantly higher amphetamine plasma levels, which did not significantly differ from those in fDA. The in vivo studies suggested that CYP2D6 is not crucial to the N-dealkylation but to another metabolic step, most probably to the ring hydroxylation. Further studies are necessary for elucidating the role of CYP2D6 in FP hydroxylation.

  14. Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature.

    Science.gov (United States)

    Pigeau; Naitoh; Buguet; McCann; Baranski; Taylor; Thompson; MacK

    1995-12-01

    Modafinil is an alerting substance that is considered safer than amphetamine with fewer side effects. Although modafinil has been used successfully to treat narcolepsy, relatively little is known about its ability to ameliorate fatigue and declines in mental performance due to sleep deprivation (SD) in a normal population. Forty-one military subjects received either 300 mg of modafinil, 20 mg of d-amphetamine, or placebo on 3 separate occasions during 64 hours of continuous cognitive work and sleep loss. Three drug treatments were given: at 23.30 hours and 05.30 hours during the first and second SD nights, respectively, and once at 15.30 hours during the third day of continuous work. Subjective estimates of mood, fatigue and sleepiness, as well as objective measures of reaction time, logical reasoning and short-term memory clearly showed better performance with both modafinil and amphetamine relative to placebo. Both modafinil and amphetamine maintained or increased body temperature compared to the natural circadian cycle observed in the placebo group. Also, from subject debriefs at the end of the study, modafinil elicited fewer side-effects than amphetamine, although more than the placebo group. Modafinil appears to be a good alternative to amphetamine for counteracting the debilitating mood and cognitive effects of sleep loss during sustained operations.

  15. Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart

    International Nuclear Information System (INIS)

    Ross, S.B.; Renyi, A.L.

    1978-01-01

    The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3 H-dopamine (DA) in striatal slices and 3 H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of the 3 H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 times more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3 H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms. (author)

  16. [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.

  17. Diazepam Inhibits Electrically Evoked and Tonic Dopamine Release in the Nucleus Accumbens and Reverses the Effect of Amphetamine.

    Science.gov (United States)

    Gomez-A, Alexander; Fiorenza, Amanda M; Boschen, Suelen L; Sugi, Adam H; Beckman, Danielle; Ferreira, Sergio T; Lee, Kendall; Blaha, Charles D; Da Cunha, Claudio

    2017-02-15

    Diazepam is a benzodiazepine receptor agonist with anxiolytic and addictive properties. Although most drugs of abuse increase the level of release of dopamine in the nucleus accumbens, here we show that diazepam not only causes the opposite effect but also prevents amphetamine from enhancing dopamine release. We used 20 min sampling in vivo microdialysis and subsecond fast-scan cyclic voltammetry recordings at carbon-fiber microelectrodes to show that diazepam caused a dose-dependent decrease in the level of tonic and electrically evoked dopamine release in the nucleus accumbens of urethane-anesthetized adult male Swiss mice. In fast-scan cyclic voltammetry assays, dopamine release was evoked by electrical stimulation of the ventral tegmental area. We observed that 2 and 3 mg of diazepam/kg reduced the level of electrically evoked dopamine release, and this effect was reversed by administration of the benzodiazepine receptor antagonist flumazenil in doses of 2.5 and 5 mg/kg, respectively. No significant effects on measures of dopamine re-uptake were observed. Cyclic voltammetry experiments further showed that amphetamine (5 mg/kg, intraperitoneally) caused a significant increase in the level of dopamine release and in the half-life for dopamine re-uptake. Diazepam (2 mg/kg) significantly weakened the effect of amphetamine on dopamine release without affecting dopamine re-uptake. These results suggest that the pharmacological effects of benzodiazepines have a dopaminergic component. In addition, our findings challenge the classic view that all drugs of abuse cause dopamine release in the nucleus accumbens and suggest that benzodiazepines could be useful in the treatment of addiction to other drugs that increase the level of dopamine release, such as cocaine, amphetamines, and nicotine.

  18. Application of gas chromatography-tandem mass spectrometry for the determination of amphetamine-type stimulants in blood and urine.

    Science.gov (United States)

    Woźniak, Mateusz Kacper; Wiergowski, Marek; Aszyk, Justyna; Kubica, Paweł; Namieśnik, Jacek; Biziuk, Marek

    2018-01-30

    Amphetamine, methamphetamine, phentermine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxy-N-ethylamphetamine (MDEA) are the most popular amphetamine-type stimulants. The use of these substances is a serious societal problem worldwide. In this study, a method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) with simple and rapid liquid-liquid extraction (LLE) and derivatization was developed and validated for the simultaneous determination of the six aforementioned amphetamine derivatives in blood and urine. The detection of all compounds was based on multiple reaction monitoring (MRM) transitions. The most important advantage of the method is the minimal sample volume (as low as 200μL) required for the extraction procedure. The validation parameters, i.e., the recovery (90.5-104%), inter-day accuracy (94.2-109.1%) and precision (0.5-5.8%), showed the repeatability and sensitivity of the method for both matrices and indicated that the proposed procedure fulfils internationally established acceptance criteria for bioanalytical methods The procedure was successfully applied to the analysis of real blood and urine samples examined in 22 forensic toxicological cases. To the best of our knowledge, this is the first work presenting the use of GC-MS/MS for the determination of amphetamine-type stimulants in blood and urine. In view of the low limits of detection (0.09-0.81ng/mL), limits of quantification (0.26-2.4ng/mL), and high selectivity, the procedure can be applied for drug monitoring in both fatal and non-fatal intoxication cases in routine toxicology analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure.

    Science.gov (United States)

    Renthal, William; Carle, Tiffany L; Maze, Ian; Covington, Herbert E; Truong, Hoang-Trang; Alibhai, Imran; Kumar, Arvind; Montgomery, Rusty L; Olson, Eric N; Nestler, Eric J

    2008-07-16

    The molecular mechanisms underlying the transition from recreational drug use to chronic addiction remain poorly understood. One molecule implicated in this process is DeltaFosB, a transcription factor that accumulates in striatum after repeated drug exposure and mediates sensitized behavioral responses to psychostimulants and other drugs of abuse. The downstream transcriptional mechanisms by which DeltaFosB regulates drug-induced behaviors are incompletely understood. We reported previously the chromatin remodeling mechanisms by which DeltaFosB activates the expression of certain genes; however, the mechanisms underlying DeltaFosB-mediated gene repression remain unknown. Here, we identify c-fos, an immediate early gene rapidly induced in striatum after acute psychostimulant exposure, as a novel downstream target that is repressed chronically by DeltaFosB. We show that accumulation of DeltaFosB in striatum after chronic amphetamine treatment desensitizes c-fos mRNA induction to a subsequent drug dose. DeltaFosB desensitizes c-fos expression by recruiting histone deacetylase 1 (HDAC1) to the c-fos gene promoter, which, in turn, deacetylates surrounding histones and attenuates gene activity. Accordingly, local knock-out of HDAC1 in striatum abolishes amphetamine-induced desensitization of the c-fos gene. In concert, chronic amphetamine increases histone H3 methylation on the c-fos promoter, a chromatin modification also known to repress gene activity, as well as expression levels of the H3 histone methyltransferase, KMT1A (lysine methyltransferase 1A, formerly SUV39H1). This study reveals a novel epigenetic pathway through which DeltaFosB mediates distinct transcriptional programs that may ultimately alter behavioral plasticity to chronic amphetamine exposure.

  20. Self-reports of consumption of amphetamines, cocaine and heroin in a survey among marginalized drug users

    OpenAIRE

    Amundsen, Ellen Johanna; Reid, Malcolm James

    2014-01-01

    - Scientific literature offers few measurements of the quantities consumed by individual drug users. Such measurements are used for calculating the total drug consumption by the quantity-frequency method, and are extremely important for the comparison with waste water derived consumption estimates. The aim of this study was to measure quantities of amphetamines, cocaine and heroin consumed by marginalized drug users, using a multi-city questionnaire survey design. Variation by gender, age,...

  1. Some effects of prenatal exposure to d-amphetamine sulfate and phenobarbital on developmental neurochemistry and on behavior.

    Science.gov (United States)

    Zemp, J W; Middaugh, L D

    1975-01-01

    Amphetamine. Prenatal intraperitoneal injection of d-amphetamine sulfate (5 mg/kg) produces decreases in the levels of catecholamines in the brain the day of birth and increases on day 30. Open-field activity from days 12 to 31 was higher for the group of animals injected with amphetamine or saline if scores were totaled across all test days. At day 75 the offspring of amphetamine-injected mothers exhibited altered open-field behavior. The effects were not observed with subcutaneous injection regardless of the dose used (2.5, 5.0, and 10.0 mg/kg). The lowest subcutaneous dose decreases neonatal viability. Phenobarbital. Prenatal intraperitoneal injection of phenobarbital (80 mg/kg) resulted in decreased litter size, increases mortality, and decreased amounts of nucleic acid and protein in the brains of surviving offspring. Behavioral deficits associated with response perseveration could be demonstrated at 60 days in the mice prenatally exposed to this dosage. Subcutaneous injections of phenobarbital to pregnant mice at 80 and 40 mg/kg, but not 20 mg/kg, doses increased neonatal mortality. Mature animals prenatally exposed to 40 mg/kg phenobarbital have altered open-field behavior and differ from control animals on a passive avoidance task. Mature offspring prenatally exposed to the 20 or 40 mg/kg dose also responded less than controls on an operant task requiring an increasing number of responses per reinforcement. These studies suggest that prenatal exposure to phenobarbital has in some way altered the animals' reactivity to stimualtion.

  2. Correlation of individual differences in schizotypal personality traits with amphetamine-induced dopamine release in striatal and extrastriatal brain regions.

    Science.gov (United States)

    Woodward, Neil D; Cowan, Ronald L; Park, Sohee; Ansari, M Sib; Baldwin, Ronald M; Li, Rui; Doop, Mikisha; Kessler, Robert M; Zald, David H

    2011-04-01

    Schizotypal personality traits are associated with schizophrenia spectrum disorders, and individuals with schizophrenia spectrum disorders demonstrate increased dopamine transmission in the striatum. The authors sought to determine whether individual differences in normal variation in schizotypal traits are correlated with dopamine transmission in the striatum and in extrastriatal brain regions. Sixty-three healthy volunteers with no history of psychiatric illness completed the Schizotypal Personality Questionnaire and underwent positron emission tomography imaging with [(18)F]fallypride at baseline and after administration of oral d-amphetamine (0.43 mg/kg). Dopamine release, quantified by subtracting each participant's d-amphetamine scan from his or her baseline scan, was correlated with Schizotypal Personality Questionnaire total and factor scores using region-of-interest and voxel-wise analyses. Dopamine release in the striatum was positively correlated with overall schizotypal traits. The association was especially robust in the associative subdivision of the striatum. Voxel-wise analyses identified additional correlations between dopamine release and schizotypal traits in the left middle frontal gyrus and left supramarginal gyrus. Exploratory analyses of Schizotypal Personality Questionnaire factor scores revealed correlations between dopamine release and disorganized schizotypal traits in the striatum, thalamus, medial prefrontal cortex, temporal lobe, insula, and inferior frontal cortex. The association between dopamine signaling and psychosis phenotypes extends to individual differences in normal variation in schizotypal traits and involves dopamine transmission in both striatal and extrastriatal brain regions. Amphetamine-induced dopamine release may be a useful endophenotype for investigating the genetic basis of schizophrenia spectrum disorders.

  3. 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.

  4. Fluctuation of the dopamine uptake inhibition potency of cocaine, but not amphetamine, at mammalian cells expressing the dopamine transporter

    Science.gov (United States)

    Ukairo, Okechukwu T.; Ramanujapuram, Suneetha; Surratt, Christopher K.

    2007-01-01

    Cocaine, amphetamines and other psychostimulants inhibit synaptic dopamine uptake by interfering with dopamine transporter (DAT) function. The resultant potentiation of dopaminergic neurotransmission is associated with psychostimulant addiction. Fluctuations in dopamine uptake inhibition potency (DUIP) were observed for classical DAT blockers including cocaine, mazindol, methylphenidate (Ritalin™) and benztropine in CHO cells expressing wildtype DAT; cocaine potency also decreased in DAT-expressing non-neuronal COS-7 cells and neuronal N2A neuroblastoma cells. In contrast, the DAT substrate (+)-amphetamine did not display this DUIP fluctuation. In parallel experiments, no fluctuation was observed for the apparent binding affinities of these 5 drugs. The DUIP decrease appeared to correlate with an increase in cell surface DAT expression level, as measured by Bmax values and confocal microscopy. The fact that the DUIP profile of amphetamine diverged from that of the classical DAT blockers is consistent with the idea of fundamental differences between the mechanisms of abused psychostimulant DAT substrates and inhibitors. Identification of the cellular factors that underlie the DAT inhibitor DUIP fluctuation phenomenon may be relevant to anti-psychostimulant drug discovery efforts. PMID:17169338

  5. Development and Validation of the Amphetamine-Type Stimulants Motive Questionnaire in a Clinical Population

    Directory of Open Access Journals (Sweden)

    Daniela Thurn

    2017-09-01

    Full Text Available Approximately 35.7 million people world-wide use amphetamine-type stimulants (ATS leading to a high demand for effective treatment. Understanding the motives behind ATS use is a necessary basis for preventive and therapeutic treatment. The objective of this study is to develop the Amphetamine-Type stimulants Motive Questionnaire (AMQ and to confirm its construct and concurrent validity in respect to the first and the latest month of ATS use based on answers of 233 patients with ATS disorders (74.2% male; mean age: 31.1 years. Confirmatory factor analyses were employed to test for the construct validity of the AMQ. Nested models of confirmatory factor analyses with increasing constraints for gender and age were estimated to test the equivalence of the factor structure in different subgroups. Independent sample t-tests were conducted to test for mean differences in the motive dimensions. A structural equation model was estimated to confirm the concurrent validity using the latent four motive factors (i.e., enhancement, coping, social, and conformity motives as independent variables and frequency of ATS use in the first and the latest month of use as a dependent variable. The results confirmed the AMQ’s four-dimensional factor structure in general, and across gender and age groups for both periods of time. Men (first month: M = 4.21, SD = 0.75; latest month: M = 3.86, SD = 0.93 use ATS more frequently due to enhancement motives than women (first month: M = 3.85, SD = 1.12; latest month: M = 3.46, SD = 1.29 at both periods of time [first month: t(77 = −2.33, p = 0.022; latest month: t(80 = −2.19, p = 0.031]. Structural equation modeling confirmed an association between coping motives and use frequency, for both periods of time (first and latest month: β = 0.32, p < 0.001, as well as between social motives and frequency of use for the latest month of use (β = 0.30, p < 0.01. To

  6. Modeling chronic brain exposure to amphetamines using primary rat neuronal cortical cultures.

    Science.gov (United States)

    Nogueira, T B; da Costa Araújo, S; Carvalho, F; Pereira, F C; Fernandes, E; Bastos, M L; Costa, V M; Capela, J P

    2014-09-26

    Amphetamine-type psychostimulants (ATS) are used worldwide by millions of patients for several psychiatric disorders. Amphetamine (AMPH) and "ecstasy" (3,4-methylenedioxymethamphetamine or MDMA) are common drugs of abuse. The impact of chronic ATS exposure to neurons and brain aging is still undisclosed. Current neuronal culture paradigms are designed to access acute ATS toxicity. We report for the first time a model of chronic exposure to AMPH and MDMA using long-term rat cortical cultures. In two paradigms, ATS were applied to neurons at day 1 in vitro (DIV) (0, 1, 10 and 100 μM of each drug) up to 28 days (200 μM was applied to cultures up to 14 DIV). Our reincubation protocol assured no decrease in the neuronal media's drug concentration. Chronic exposure of neurons to concentrations equal to or above 100 μM of ATS up to 28 DIV promoted significant mitochondrial dysfunction and elicited neuronal death, which was not prevented by glutamate receptor antagonists at 14 DIV. ATS failed to promote accelerated senescence as no increase in β-galactosidase activity at 21 DIV was found. In younger cultures (4 or 8 DIV), AMPH promoted mitochondrial dysfunction and neuronal death earlier than MDMA. Overall, AMPH proved more toxic and was the only drug that decreased intraneuronal glutathione levels. Meanwhile, caspase 3 activity increased for either drug at 200 μM in younger cultures at 8 DIV, but not at 14 DIV. At 8 DIV, ATS promoted a significant change in the percentage of neurons and astroglia present in culture, promoting a global decrease in the number of both cells. Importantly, concentrations equal to or below 10 μM of either drug did not promote neuronal death or oxidative stress. Our paradigm of neuronal cultures long-term exposure to low micromolar concentrations of ATS closely reproduces the in vivo scenario, being valuable to study the chronic impact of ATS. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. 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

  8. 123I-amphetamine-SPECT in the diagnosis of neurological disorders

    International Nuclear Information System (INIS)

    Biersack, H.J.; Kreiten, K.; Hartmann, A.; Friedrich, G.; Linck, H.A.; Winkler, C.; Bonn Univ.; Rheinische Landesklinik, Bonn

    1985-01-01

    In contrast to conventional brain scintigraphy with sup(99m)Tc-pertechnetate, SPECT with 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 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. (orig.) [de

  9. DNA-based MRI probes for specific detection of chronic exposure to amphetamine in living brains.

    Science.gov (United States)

    Liu, Christina H; Ren, Jia Q; Yang, Jinsheng; Liu, Charng-ming; Mandeville, Joseph B; Rosen, Bruce R; Bhide, Pradeep G; Yanagawa, Yuchio; Liu, Philip K

    2009-08-26

    We designed phosphorothioate-modified DNA probes linked to superparamagnetic iron oxide nanoparticles (SPION) for in vivo magnetic resonance imaging (MRI) of fosB and Delta fosB mRNA after amphetamine (AMPH) exposure in mice. Specificity of both the fosB and Delta fosB probes was verified by in vitro reverse transcriptase-PCR amplification to a single fragment of total cDNA obtained from acutely AMPH-exposed mouse brains. We confirmed time-dependent uptake and retention profiles of both probes in neurons of GAD67-green fluorescent protein knock-in mice. MRI signal of SPION-labeled fosB probe delivered via intracerebroventricular route was elevated in both acutely and chronically AMPH-exposed mice; the signal was suppressed by dopaminergic receptor antagonist pretreatment. SPION-labeled Delta fosB probe signal elevation occurred only in chronically AMPH-exposed mice. The in vivo target specificity of these probes permits reliable MRI visualization of AMPH-induced differential elevations of fosB and Delta fosB mRNA in living brains.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. 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 samples taken from individuals whose blood had screened positive for drugs of abuse. All the individuals screened positive for COC in the blood (seven samples) also had positive results in VH; COC concentration ranged from 30.81 to 283.97 ng/mL (mean 186.98 ng/mL) and benzoylecgonine concentration ranged from 11.47 to 460.98 ng/mL (mean 133.91 ng/mL). It was also noticed that, in five cases, cocaethylene was detected. AEME was also quantified in one case. The use of AMP detected by blood analysis was confirmed in the VH of one individual (24.31 ng/mL). However, samples taken from three individuals whose blood tested positive for carboxy-tetrahydrocannabinol presented negative results. The results demonstrated that VH is a suitable alternative biological sample to determine COC, AMPs, opiates and their metabolites.

  13. False-Positive TDxFLx urine Amphetamine/Metamphetamine II assay from Ofloxacin

    International Nuclear Information System (INIS)

    Nomier, Mahmoud A.; Al-Huseini, Hani K.

    2004-01-01

    Immunoassays are widely used in testing urine for illicit drugs. Ofloaxcin and a number of other quinolones were found to induce false-positive opiates (OP) urine immunoassays. This can result in misleading conclusions in the concept of drug abuse The aim of present study was to evaluate the effects of ofloxacin in theraputic doses on the induction of false-positive urine immunoassays for common drugs of abuse in healthy male volunteers. The study was conducted on 6 healthy male volunteers, aging between 35-45 years. Two doses of 400 mg ofloxacin each, were given orally to each volunteer at 12 hours interval and urine samples were collected before ofloaxcin administration and 5-7.5 hours after the second dose. Urine samples were subjected for OP, amphetamine/methamphetamine II (AM/MA II), cocaine and cannabinoids assays on TDxFLx analyzer. Ofloxacin produced significant increase (P cutoff) for AM/MA II assays, were found in all volunteers after ofloaxcin administration. The study recomends strongly the confirmation of positive urine immunoassay results for drugs of abuseby a more specific methodology e.g. gas chromatography/ mass spectroscopy (GC/MS). (author)

  14. 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.

  15. Trends in counterfeits amphetamine-type stimulants after its prohibition in Brazil.

    Science.gov (United States)

    Mariotti, Kristiane de Cássia; Ortiz, Rafael S; Souza, Daniele Z; Mileski, Thayse C; Fröehlich, Pedro E; Limberger, Renata P

    2013-06-10

    Brazil is one of the world's highest users of anorectic drugs, mainly diethylpropione, fenproporex and sibutramine. The present work focuses on physical and chemical characteristics of 17 counterfeited capsules containing amphetamine-type stimulants (ATS) from three seizures conducted by Brazilian Federal Police. The physical profile was useful in indicating forgery, bring complementary information, but the use of this data singly was not sufficient to distinguish between authentic and counterfeited medicines. The chemical analysis revealed that the seizures capsules labeled as Desobesi-M (fenproporex 25mg), actually contained the active pharmaceutical ingrediente (API) sibutramine. The amount of this API ranged from 1/3 to 2 times the amount of drug found in commercial product, may reach twice the recommended daily dose. Multivariate analysis with application of principal component analysis on data from spectroscopy attenuated total reflectance Fourier transform infrared classified the samples according to their similarities, indicating that two seizures had common origin. This study represents the first step in the elucidation of falsification of ATS in Brazil. Considering the forensic intelligence these information are valuable in order to develop and establish a database that enables correlate samples from different locations and/or suppliers and to map the profile and trends of trafficking. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. 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'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Neuronal Adaptation to Amphetamine and Dopamine: Molecular Mechanisms of Prodynorphin Gene Regulation in Rat Striatum

    Science.gov (United States)

    Cole, Rebecca L.; Konradi, Christine; Douglass, James; Hyman, Steven E.

    2014-01-01

    Summary Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three recently described cAMP response elements (CREs), rather than a previously reported noncanonical AP-1 site, are critical for dopamine induction of the prodynorphin gene in striatal neurons. CRE-binding protein (CREB) binds to these CREs in striatal cell extracts and is phosphorylated on Ser-133 after dopamine stimulation in a D1 dopamine receptor-dependent manner. Surprisingly, following chronic administration of amphetamine, levels of phosphorylated CREB are increased above basal in rat striatum in vivo, whereas c-fos mRNA is suppressed below basal levels. D1 receptor-mediated CREB phosphorylation appears to mediate adaptations to psychostimulant drugs in the striatum. PMID:7718243

  18. Detection of Delta9-tetrahydrocannabinol and amphetamine-type stimulants in oral fluid using the Rapid Stat point-of-collection drug-testing device.

    Science.gov (United States)

    Röhrich, J; Zörntlein, S; Becker, J; Urban, R

    2010-04-01

    The Rapid Stat assay, a point-of-collection drug-testing device for detection of amphetamines, cannabinoids, cocaine, opiates, methadone, and benzodiazepines in oral fluid, was evaluated for cannabis and amphetamine-type stimulants. The Rapid Stat tests (n = 134) were applied by police officers in routine traffic checks. Oral fluid and blood samples were analyzed using gas chromatography-mass spectrometry (GC-MS) for Delta(9)-tetrahydrocannabinol, amphetamine, methamphetamine, methylenedioxymethamphetamine, methylenedioxyethylamphetamine, and methylenedioxyamphetamine. The comparison of GC-MS analysis of oral fluid with the Rapid Stat results for cannabis showed a sensitivity of 85%, a specificity of 87%, and a total confirmation rate of 87%. When compared with serum, the sensitivity of the cannabis assay decreased to 71%, the specificity to 60%, and the total confirmation rate to 66%. These findings were possibly caused by an incorrect reading of the THC test results. Comparison of the Rapid Stat amphetamine assay with GC-MS in oral fluid showed a sensitivity of 94%, a specificity of 97%, and a total confirmation rate of 97%. Compared with serum, a sensitivity of 100%, a specificity of 90%, and a total confirmation rate of 92% was found. The amphetamine assay must, therefore, be regarded as satisfactory.

  19. A Single-Dose, Two-Way Crossover, Open-Label Bioequivalence Study of an Amphetamine Extended-Release Oral Suspension in Healthy Adults.

    Science.gov (United States)

    Sikes, Carolyn; Stark, Jeffrey G; McMahen, Russ; Engelking, Dorothy

    2017-11-01

    The purpose of this study was to compare the pharmacokinetics of a new extended-release amphetamine oral suspension (AMP XR-OS) with a standard extended-release mixed amphetamine salts product, Adderall XR®. In this single-dose, open-label, randomized, two-period, two-treatment crossover study, 42 healthy adult volunteers received 15 mL of AMP XR-OS in one period and a 30 mg Adderall XR capsule in another period (both containing 18.8 mg of amphetamine base) under fasted conditions. Blood samples were analyzed for d- and l-amphetamine concentrations, and pharmacokinetic parameters C max , AUC 0-5 , AUC 5-last , and AUC inf were calculated to determine bioequivalence. Safety was monitored throughout the study. The 90% confidence intervals (CIs) for the log-transformed C max , AUC 0-5 , AUC 5-last , and AUC inf fell within the accepted 80% to 125% range for establishing bioequivalence for d- and l-amphetamine. The most common adverse events were nausea and decreased appetite. AMP XR-OS is bioequivalent to Adderall XR in healthy adult participants.

  20. Interactions of [3H]amphetamine with rat brain synaptosomes. II. Active transport

    International Nuclear Information System (INIS)

    Zaczek, R.; Culp, S.; De Souza, E.B.

    1991-01-01

    The accumulation of 5 nM d-[ 3 H]amphetamine (d-[ 3 H]AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-[ 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-[ 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 [ 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-[ 3 H]AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed

  1. Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

    Science.gov (United States)

    Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

    2012-10-01

    Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

  2. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory.

    Science.gov (United States)

    Lapish, Christopher C; Balaguer-Ballester, Emili; Seamans, Jeremy K; Phillips, Anthony G; Durstewitz, Daniel

    2015-07-15

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of appropriate statistical methods required to assess attractor-like behavior in vivo. The present study used a combination of advanced multivariate statistical, time series analysis, and machine learning methods to assess dynamic changes in network activity from multiple single-unit recordings from the medial prefrontal cortex (mPFC) of rats while the animals performed a foraging task guided by working memory after pretreatment with different doses of d-amphetamine (AMPH), which increases monoamine efflux in the mPFC. A dose-dependent, bidirectional effect of AMPH on neural dynamics in the mPFC was observed. Specifically, a 1.0 mg/kg dose of AMPH accentuated separation between task-epoch-specific population states and convergence toward these states. In contrast, a 3.3 mg/kg dose diminished separation and convergence toward task-epoch-specific population states, which was paralleled by deficits in cognitive performance. These results support the computationally derived hypothesis that moderate increases in monoamine efflux would enhance attractor stability, whereas high frontal monoamine levels would severely diminish it. Furthermore, they are consistent with the proposed inverted U-shaped and concentration-dependent modulation of cortical efficiency by monoamines. Copyright © 2015 the authors 0270-6474/15/3510172-16$15.00/0.

  3. The Effects of Oral d-Amphetamine on Impulsivity in Smoked and Intranasal Cocaine Users

    Science.gov (United States)

    Reed, Stephanie Collins; Evans, Suzette M.

    2016-01-01

    BACKGROUND Effective treatments for cocaine use disorders remain elusive. Two factors that may be related to treatment failures are route of cocaine used and impulsivity. Smoked cocaine users are more likely to have poorer treatment outcomes compared to intranasal cocaine users. Further, cocaine users are impulsive and impulsivity is associated with poor treatment outcomes. While stimulants are used to treat Attention Deficit Hyperactivity Disorder (ADHD) and attenuate certain cocaine-related behaviors, few studies have comprehensively examined whether stimulants can reduce behavioral impulsivity in cocaine users, and none examined route of cocaine use as a factor. METHODS The effects of immediate release oral d-amphetamine (AMPH) were examined in 34 cocaine users (13 intranasal, 21 smoked). Participants had three separate sessions where they were administered AMPH (0, 10, or 20 mg) and completed behavioral measures of impulsivity and risk-taking and subjective measures of abuse liability. RESULTS Smoked cocaine users were more impulsive on the Delayed Memory Task, the GoStop task and the Delay Discounting Task than intranasal cocaine users. Smoked cocaine users also reported more cocaine craving and negative mood than intranasal cocaine users. AMPH produced minimal increases on measures of abuse liability (e.g., Drug Liking). CONCLUSIONS Smoked cocaine users were more impulsive than intranasal cocaine users on measures of impulsivity that had a delay component. Additionally, although AMPH failed to attenuate impulsive responding, there was minimal evidence of abuse liability in cocaine users. These preliminary findings need to be confirmed in larger samples that control for route and duration of cocaine use. PMID:27114203

  4. Amphetamine modulates brain signal variability and working memory in younger and older adults.

    Science.gov (United States)

    Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

    2015-06-16

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

  5. 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.

  6. 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.

  7. Differential influence of dopamine transport rate on the potencies of cocaine, amphetamine, and methylphenidate.

    Science.gov (United States)

    Calipari, Erin S; Ferris, Mark J; Siciliano, Cody A; Jones, Sara R

    2015-01-21

    Dopamine transporter (DAT) levels vary across brain regions and individuals, and are altered by drug history and disease states; however, the impact of altered DAT expression on psychostimulant effects in brain has not been systematically explored. Using fast scan cyclic voltammetry, we measured the effects of elevated DAT levels on presynaptic dopamine parameters as well as the uptake inhibition potency of the blockers cocaine and methylphenidate (MPH) and the releaser amphetamine (AMPH) in the nucleus accumbens core. Here we found that increases in DAT levels, resulting from either genetic overexpression or MPH self-administration, caused markedly increased maximal rates of uptake (Vmax) that were positively correlated with the uptake inhibition potency of AMPH and MPH, but not cocaine. AMPH and MPH were particularly sensitive to DAT changes, with a 100% increase in Vmax resulting in a 200% increase in potency. The relationship between Vmax and MPH potency was the same as that for AMPH, but was different from that for cocaine, indicating that MPH more closely resembles a releaser with regard to uptake inhibition. Conversely, the effects of MPH on stimulated dopamine release were similar to those of cocaine, with inverted U-shaped increases in release over a concentration-response curve. This was strikingly different from the release profile of AMPH, which showed only reductions at high concentrations, indicating that MPH is not a pure releaser. These data indicate that although MPH is a DAT blocker, its uptake-inhibitory actions are affected by DAT changes in a similar manner to releasers. Together, these data show that fluctuations in DAT levels alter the potency of releasers and MPH but not blockers and suggest an integral role of the DAT in the addictive potential of AMPH and related compounds.

  8. Effect of Amphetamine on Adult Male and Female Rats Prenatally Exposed to Methamphetamine

    Directory of Open Access Journals (Sweden)

    Romana Šlamberová

    2014-01-01

    Full Text Available The aim of the present study was to examine the cross-sensitization induced by prenatal methamphetamine (MA exposure to adult amphetamine (AMP treatment in male and female rats. Rat mothers received a daily injection of MA (5 mg/kg or saline throughout the gestation period. Adult male and female offspring (prenatally MA- or saline-exposed were administered with AMP (5 mg/kg or saline (1 ml/kg in adulthood. Behaviour in unknown environment was examined in open field test (Laboras, active drug-seeking behaviour in conditioned place preference test (CPP, spatial memory in the Morris water maze (MWM, and levels of corticosterone (CORT were analyzed by enzyme immunoassay (EIA. Our data demonstrate that in Laboras test, AMP treatment in adulthood increased general locomotion (time and distance travelled regardless of the prenatal exposure and sex, while AMP increased exploratory activity (rearing only in prenatally MA-exposed animals. AMP induced sensitization only in male rats, but not in females when tested drug-seeking behaviour in the CPP test. In the spatial memory MWM test, AMP worsened the performance only in females, but not in males. On the other hand, males swam faster after chronic AMP treatment regardless of the prenatal drug exposure. EIA analysis of CORT levels demonstrated higher level in females in all measurement settings. In males, prenatal MA exposure and chronic adult AMP treatment decreased CORT levels. Thus, our data demonstrated that adult AMP treatment affects behaviour of adult rats, their spatial memory and stress response in sex-specific manner. The effect is also influenced by prenatal drug exposure.

  9. Recent trends in the availability and use of amphetamine and methamphetamine in Norway.

    Science.gov (United States)

    Bramness, Jørgen G; Reid, Malcolm J; Solvik, Kari Frey; Vindenes, Vigdis

    2015-01-01

    There is a concern about methamphetamine use in Europe. Methamphetamine fatalities have recently occurred in Southern European countries. The aim of this study is to examine Norwegian methamphetamine trends in recent years, comparing different data sources. Data about amphetamines were collected from five different sources; blood samples from drivers suspected of driving under the influence of drugs and apprehended by the police (during the years 2000-2012), urine samples from inmates in Norwegian prisons (during 2000-2012), post-mortem blood samples from medico-legal autopsies (2000-2012), drug seizures (1994-2012) and wastewater samples from a metropolitan/suburban population (2010-2012). The number of cases where methamphetamine was detected has increased during the period studied for the driving under the influence cases, the samples from inmates and from forensic autopsies. The increase seems to be linear up to 2009-2010, with a subsequent stabilisation or even a decline in the market share of methamphetamine for the next few years. The number of methamphetamine seizures has risen from less than 1% in 2000 to approximately 66% in 2009, and a steady share around 60% have been seen between 2010 and 2012. Wastewater samples showed that the share of methamphetamine peaked in 2010-11, before falling. It is difficult to obtain reliable data on illicit drugs. Data from different populations might give indications of changes and trends, but are always prone to different biases. By comparing results from different data sources, a better knowledge of the illicit drug market might be obtained. All our data sources confirmed that methamphetamine became a more prevalent drug during the first decade of the new millennium in Norway, but since approximately 2009 the share of methamphetamine stabilised. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    de Jong, Jelly G; Wasilewski, Michal; van der Vegt, Bea J; Buwalda, Bauke; Koolhaas, Jaap M

    2005-01-17

    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 potential of a single exposure to stress is not clear. Both drug- and stress-induced sensitization depend on an enhanced dopaminergic neurotransmission in the mesolimbic DA system. Apart from responding to rewards, this system is also involved in responding towards aversive social stimuli. Therefore, social stressors may be particularly effective in inducing cross-sensitization to stimulant drugs. We examined the time course of sensitization to the locomotor effects of the stimulant, AMPH, following a single social stressor: a social defeat. Wistar rats were exposed in a resident-intruder paradigm to an unfamiliar dominant male conspecific (Wild-Type Groningen), resulting in defeat. The locomotor effects of a subsequent AMPH challenge (0.25 or 1.0 mg/kg) were evaluated 3, 14, and 21 days later by scoring horizontal movement in an open field. AMPH had significantly larger locomotor-activating effects in animals that had been defeated 3 days earlier compared to nondefeated controls. However, this sensitized response was no longer present 14 or 21 days after defeat. Therefore, we conclude that social defeat induces short-lasting cross-sensitization to the locomotor effects of AMPH in rats, but is not sufficient for long-term sensitization. The transient enhancement of responses to dopaminergic drugs may be indicative of a temporary role of dopamine in the cascade of physiological and behavioral changes following social defeat.

  11. Nucleus accumbens cocaine-amphetamine regulated transcript mediates food intake during novelty conflict

    Science.gov (United States)

    Burghardt, PR; Krolewski, DM; Dykhuis, KE; Ching, J; Pinawin, AM; Britton, SL; Koch, LG; Watson, SJ; Akil, H.

    2016-01-01

    Obesity is a persistent and pervasive problem, particularly in industrialized nations. It has come to be appreciated that the metabolic health of an individual can influence brain function and subsequent behavioral patterns. To examine the relationship between metabolic phenotype and central systems that regulate behavior, we tested rats with divergent metabolic phenotypes (Low Capacity Runner: LCR vs. High Capacity Runner: HCR) for behavioral responses to the conflict between hunger and environmental novelty using the novelty suppressed feeding (NSF) paradigm. Additionally, we measured expression of mRNA, for peptides involved in energy management, in response to fasting. Following a 24-h fast, LCR rats showed lower latencies to begin eating in a novel environment compared to HCR rats. A 48-h fast equilibrated the latency to begin eating in the novel environment. A 24-h fast differentially affected expression of cocaine-amphetamine regulated transcript (CART) mRNA in the nucleus accumbens (NAc), where 24-h of fasting reduced CART mRNA in LCR rats. Bilateral microinjections of CART 55–102 peptide into the NAc increased the latency to begin eating in the NSF paradigm following a 24-h fast in LCR rats. These results indicate that metabolic phenotype influences how animals cope with the conflict between hunger and novelty, and that these differences are at least partially mediated by CART signaling in the NAc. For individuals with poor metabolic health who have to navigate food-rich and stressful environments, changes in central systems that mediate conflicting drives may feed into the rates of obesity and exacerbate the difficulty individuals have in maintaining weight loss. PMID:26926827

  12. [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.

  13. 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Novel Selectivity-Based Forensic Toxicological Validation of a Paper Spray Mass Spectrometry Method for the Quantitative Determination of Eight Amphetamines in Whole Blood

    Science.gov (United States)

    Teunissen, Sebastiaan F.; Fedick, Patrick W.; Berendsen, Bjorn J. A.; Nielen, Michel W. F.; Eberlin, Marcos N.; Graham Cooks, R.; van Asten, Arian C.

    2017-12-01

    Paper spray tandem mass spectrometry is used to identify and quantify eight individual amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy- N-methylamphetamine (MDMA), 3,4-methylenedioxy- N-ethylamphetamine (MDEA), para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), and 4-fluoroamphetamine (4-FA). Additionally, a new concept of intrinsic and application-based selectivity is discussed, featuring increased confidence in the power to discriminate the amphetamines from other chemically similar compounds when applying an ambient mass spectrometric method without chromatographic separation. Accuracy was within ±15% and average precision was better than 15%, and better than 20% at the LLOQ. Detection limits between 15 and 50 ng/mL were obtained using only 12 μL of whole blood. [Figure not available: see fulltext.

  15. Chronic caffeine produces sexually dimorphic effects on amphetamine-induced behavior, anxiety and depressive-like behavior in adolescent rats.

    Science.gov (United States)

    Turgeon, Sarah M; Townsend, Shannon E; Dixon, Rushell S; Hickman, Emma T; Lee, Sabrina M

    2016-04-01

    Caffeine consumption has been increasing rapidly in adolescents; however, most research on the behavioral effects of caffeine has been conducted in adults. Two experiments were conducted in which adolescent male and female rats were treated with a moderate dose of caffeine (0.25 g/l) in their drinking water beginning on P26-28. In the first experiment, animals were maintained on caffeinated drinking water or normal tap water for 14 days and were then tested for behavioral and striatal c-Fos response to amphetamine (1.5 mg/kg). In the second experiment, rats were maintained on caffeinated drinking water or normal tap water beginning on P28 and were tested for novel object recognition, anxiety in the light/dark test (L/D) and elevated plus maze (EPM), and depressive like behavior in the forced swim test (FST) beginning on the 14th day of caffeine exposure. Caffeine decreased amphetamine-induced rearing in males, but had no effect in females; however, this behavioral effect was not accompanied by changes in striatal c-Fos, which was increased by amphetamine but not altered by caffeine. No effects of caffeine were observed on novel object recognition or elevated plus maze behavior. However, in the L/D test, there was a sex by caffeine interaction on time spent in the light driven by a caffeine-induced increase in light time in the males but not the females. On the pretest day of the FST, sex by caffeine interactions were observed for swimming and struggling; caffeine decreased struggling behavior and increased swimming behavior in males and caffeine-treated females demonstrated significantly more struggling and significantly less swimming than caffeine-treated males. A similar pattern was observed on the test day in which caffeine decreased immobility overall and increased swimming. These data reveal sex dependent effects of caffeine on behavior in adolescent rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 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.

  17. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

    Science.gov (United States)

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2016-11-01

    Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h, i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15-21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1mg/kg per injection cocaine availability. Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Odor-avoidance or odor-preference induced by amphetamine in the infant rat depending on the dose and testing modality.

    Science.gov (United States)

    Revillo, Damian A; Fernandez, Guillermo; Castello, Stefania; Paglini, Maria Gabriela; Arias, Carlos

    2012-05-16

    By the second postnatal week of life infant rats can acquire taste avoidance induced by amphetamine. Psychostimulant drugs supports appetitive and aversive learning in adult rats. Their appetitive effects are more likely to become associated with contextual cues, while the aversive ones have been consistently found in taste aversion learning. To explain this paradox, it has been proposed that rats would avoid a taste that predicts a change in their homeostasis because this species cannot vomit. In this study we assessed the motivational properties of amphetamine in preweanling rats by means of an odor conditioning preparation, which enables the analysis of the hedonic value of the memory by means of a consumption test or in terms of locomotor approach to the odor. Results indicate that regardless of the amphetamine dose (1 or 5 mg/kg), when animals were evaluated in the intake test, subjects avoided the odor. However, the outcome in the locomotor avoidance test varied as a function of the amphetamine dose. Rats trained with the low dose (1 mg/kg) showed odor preference, while the highest amphetamine dose (5 mg/kg) induced odor avoidance. When LiCl was employed as an unconditioned stimulus (US), rats showed avoidance in the intake and locomotor activity tests. These data indicate that amphetamine, like other drugs of abuse, supports appetitive conditioning in preweanling rats. Interestingly, infant rats expressed conditioned odor avoidance or preference depending on the dose and testing modality. Results were discussed considering current theories of avoidance learning induced by rewarding drugs. Copyright © 2012 Elsevier B.V. All rights reserved.

  19. Amphetamines analysis in wastewaters - method performance of solid phase extraction - higher performance liquid chromatography mass spectrometry techniques (SPE-HPLC MS/MS)

    Science.gov (United States)

    Mustapha, Aliru Olajide; Ajao, Usman L

    2011-01-01

    Recently, many articles have reported different levels and distribution of amphetamine hitherto detected in biological fluids now appreciably found in aquatic environment at ng/L levels. Identification and measurement of amphetamine and its metabolites in surface and sewage waters using higher performance liquid chromatographic methodologies in the literatures now on current trend have provided information that are of scientific interest and effectively replaced immunological methods which only suggest the presence of these substances. Active research on both distribution and impacts of this important drug of abuse and related metabolites in the wastewaters are on-going. PMID:27857670

  20. 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.

  1. 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.

  2. 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.

  3. Constitutive Ret signaling leads to long-lasting expression of amphetamine-induced place conditioning via elevation of mesolimbic dopamine.

    Science.gov (United States)

    Kopra, Jaakko; Villarta-Aguilera, Marian; Savolainen, Mari; Weingerl, Samo; Myöhänen, Timo T; Rannanpää, Saara; Salvatore, Michael F; Andressoo, Jaan-Olle; Piepponen, T Petteri

    2018-01-01

    Addictive drugs enhance dopamine release in the striatum, which can lead to compulsive drug-seeking after repeated exposure. Glial cell line-derived neurotrophic factor (GDNF) is an important regulator of midbrain dopamine neurons, and may play a mechanistic role in addiction-related behaviors. To elucidate the components of GDNF-signaling that contribute to addiction-related behaviors of place preference and its extinction, we utilized two genetically modified GDNF mouse models in an amphetamine-induced conditioned place preference (CPP) paradigm and evaluated how the behavioral findings correlate with dopamine signaling in the dorsal and ventral striatum. We utilized two knock-in mouse strains to delineate contributions of GDNF and Ret signaling using MEN2B mice (constitutively active GDNF receptor Ret), and GDNF hypermorphic mice (enhanced endogenous GDNF expression). The duration of amphetamine-induced CPP was greatly enhanced in MEN2B mice, but not in the GDNF hypermorphic mice. The enhanced duration of CPP was correlated with increased tyrosine hydroxylase (TH) expression and dopamine content in the ventral striatum. Together, our results suggest that downstream components of GDNF signaling, in this case Ret, may mediate persistent drug-seeking behavior through increased TH expression and dopamine levels in the mesolimbic dopamine neurons. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

    Souza, Daniele Z; Boehl, Paula O; Comiran, Eloisa; Mariotti, Kristiane C; Pechansky, Flavio; Duarte, Paulina C A V; De Boni, Raquel; Froehlich, Pedro E; Limberger, Renata P

    2011-06-24

    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™ 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(-1) (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL(-1). The detection limits were 0.5 ng mL(-1) (MET), 1 ng mL(-1) (MPH) and 2 ng mL(-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™ 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Simultaneous analysis of amphetamine-type stimulants in plasma by solid-phase microextraction and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Mariotti, Kristiane de Cássia; Schuh, Roselena S; Ferranti, Priscila; Ortiz, Rafael S; Souza, Daniele Z; Pechansky, Flavio; Froehlich, Pedro E; Limberger, Renata P

    2014-09-01

    Brazil is considered one of the countries with the highest number of amphetamine-type stimulant (ATS) users worldwide, mainly diethylpropion (DIE) and fenproporex (FEN). The use of ATS is mostly linked to diverted prescription stimulants and this misuse is widely associated with (ab)use by drivers. A validated method was developed for the simultaneous analysis of amphetamine (AMP), DIE and FEN in plasma samples employing direct immersion-solid-phase microextraction, and gas chromatographic/mass spectrometric analysis. Trichloroacetic acid 10% was used for plasma deproteinization. In situ derivatization with propylchloroformate was employed. The linear range of the method covered from 5.0 to 100 ng/mL. The detection limits were 1.0 (AMP), 1.5 (DIE) and 2.0 ng/mL (FEN). The accuracy assessment of the control samples was within 85.58-108.33% of the target plasma concentrations. Recoveries ranged from 46.35 to 84.46% and precision was <15% of the value of relative standard deviation. This method is appropriate for screening and confirmation in plasma forensic toxicology analyses of these basic drugs. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Effect of amphetamine on corrected-QT interval change during methadone maintenance treatment in Taiwan: a prospective cohort study.

    Science.gov (United States)

    Lin, Ni-Chi; Huang, Chieh-Liang; Chen, Chung-Ying; Lin, Tsang-Yaw; Wang, Hsiu-Yi; Lu, Ye-Hsu; Chen, Lin-Mei; Chen, Vincent Chin-Hung; Gossop, Michael

    2014-03-01

    Previous studies have suggested that methadone is associated with prolonged corrected-QT (QTc) interval, but published prospective research studies in this area are relatively scarce. This study investigates QTc interval change among methadone maintenance patients and possible associated risk factors. One of the aims is to explore the effect of amphetamines. This prospective cohort study with six-month follow up assesses the effect of methadone on QTc interval among a sample (n = 170) of heroin users in a methadone maintenance treatment program in Taiwan. Demographic data, substance use history, medical history and laboratory studies were collected at study enrollment. Twelve-lead electrocardiograms were performed for all participants both at study enrollment and six months later. The median daily methadone dose was 41 mg. A mean increase of QTc interval (17.1 ms, SD = 50.0, P Methadone dose was not associated with QTc change. An increase of mean QTc interval was found among methadone maintenance patients at six-month follow up. Electrocardiogram monitoring should be performed among patients who are at risk of frequently using amphetamines during methadone maintenance treatment. © 2013 Australasian Professional Society on Alcohol and other Drugs.

  7. Response of the Emit II amphetamine/methamphetamine assay to specimens collected following use of Vicks inhalers.

    Science.gov (United States)

    Poklis, A; Jortani, S A; Brown, C S; Crooks, C R

    1993-09-01

    The possible cross-reactivity of l-methamphetamine (desoxyephedrine) to the Syva Emit II amphetamine/methamphetamine assay was evaluated in urine specimens collected from seven subjects using Vicks Inhalers. The subjects were six males and one female ranging from 24 to 47 years of age. Four subjects used the inhaler every two waking hours for five consecutive days, while three subjects inhaled hourly for three consecutive days. All urine voids were collected, totaling 150 specimens. All specimens were analyzed by the Emit II assay on a Hitachi 717 automatic analyzer with a 1000-ng/mL d-methamphetamine cutoff calibrator. None of the inhaler specimens produced an Emit II response equal to or greater than the cutoff calibrator; all were negative. Specimens producing the highest rates were further analyzed by chiral GC/MS. The highest concentrations of l-methamphetamine were observed in urines from two subjects inhaling hourly: 1390, 1290, and 740 ng/mL. These specimens were collected the evenings of the second and third day. When used as directed or even with double the daily dose, Vicks Inhalers did not cause false-positive results in urine tested with the Emit II Amphetamine/Methamphetamine assay.

  8. Minocycline inhibits D-amphetamine-elicited action potential bursts in a central snail neuron.

    Science.gov (United States)

    Chen, Y-H; Lin, P-L; Wong, R-W; Wu, Y-T; Hsu, H-Y; Tsai, M-C; Lin, M-J; Hsu, Y-C; Lin, C-H

    2012-10-25

    Minocycline is a second-generation tetracycline that has been reported to have powerful neuroprotective properties. In our previous studies, we found that d-amphetamine (AMPH) elicited action potential bursts in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac. This study sought to determine the effects of minocycline on the AMPH-elicited action potential pattern changes in the central snail neuron, using the two-electrode voltage clamping method. Extracellular application of AMPH at 300 μM elicited action potential bursts in the RP4 neuron. Minocycline dose-dependently (300-900 μM) inhibited the action potential bursts elicited by AMPH. The inhibitory effects of minocycline on AMPH-elicited action potential bursts were restored by forskolin (50 μM), an adenylate cyclase activator, and by dibutyryl cAMP (N(6),2'-O-Dibutyryladenosine 3',5'-cyclic monophosphate; 1mM), a membrane-permeable cAMP analog. Co-administration of forskolin (50 μM) plus tetraethylammonium chloride (TEA; 5mM) or co-administration of TEA (5mM) plus dibutyryl cAMP (1mM) also elicited action potential bursts, which were prevented and inhibited by minocycline. In addition, minocycline prevented and inhibited forskolin (100 μM)-elicited action potential bursts. Notably, TEA (50mM)-elicited action potential bursts in the RP4 neuron were not affected by minocycline. Minocycline did not affect steady-state outward currents of the RP4 neuron. However, minocycline did decrease the AMPH-elicited steady-state current changes. Similarly, minocycline decreased the effects of forskolin-elicited steady-state current changes. Pretreatment with H89 (N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride; 10 μM), a protein kinase A inhibitor, inhibited AMPH-elicited action potential bursts and decreased AMPH-elicited steady-state current changes. These results suggest that the cAMP-protein kinase A signaling pathway and the steady-state current are involved in

  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. 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...

  11. 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

  12. Molecularly imprinted polymer-sol-gel tablet toward micro-solid phase extraction: II. Determination of amphetamine in human urine samples by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    El-Beqqali, Aziza; Andersson, Lars I; Jeppsson, Amin Dadoun; Abdel-Rehim, Mohamed

    2017-09-15

    Amphetamine selective molecularly imprinted sol-gel polymer tablets, MIP-tablets, for solid-phase microextraction of biofluid samples were prepared. An acetonitrile solution of deuterated amphetamine template and silane precursor, 3-(propylmethacrylate) trimethoxysilane, was soaked into the pores of polyethylene tablet substrates and polymerized by an acid-catalysed sol-gel process. Application of the resultant MIP-tablets to extract amphetamine from human urine samples followed by LC-MS/MS analysis was investigated. The extraction protocol was optimised with respect to pH of sample, addition of sodium chloride, extraction time, desorption solvent and desorption time. The final analysis method determined amphetamine in human urine with a limit of detection (LOD) of 1.0ng/mL and a lower limit of quantification (LLOQ) of 5ng/mL. Validation demonstrated accuracy of the method was 91.0-104.0% and inter-assay precision was 4.8-8.5% (RSD). Extraction recovery was 80%. The MIP-tablets could be re-used and the same tablet could be employed for more than twenty extractions. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Relationships between the catechol substrate binding site and amphetamine, cocaine, and mazindol binding sites in a kinetic model of the striatal transporter of dopamine in vitro.

    Science.gov (United States)

    Wayment, H; Meiergerd, S M; Schenk, J O

    1998-05-01

    Experiments were conducted to determine how (-)-cocaine and S(+)-amphetamine binding sites relate to each other and to the catechol substrate site on the striatal dopamine transporter (sDAT). In controls, m-tyramine and S(+)-amphetamine caused release of dopamine from intracellular stores at concentrations > or = 12-fold those observed to inhibit inwardly directed sDAT activity for dopamine. In preparations from animals pretreated with reserpine, m-tyramine and S(+)-amphetamine caused release of preloaded dopamine at concentrations similar to those that inhibit inwardly directed sDAT activity. S(+)-Amphetamine and m-tyramine inhibited sDAT activity for dopamine by competing for a common binding site with dopamine and each other, suggesting that phenethylamines are substrate analogues at the plasmalemmal sDAT. (-)-Cocaine inhibited sDAT at a site separate from that for substrate analogues. This site is mutually interactive with the substrate site (K(int) = 583 nM). Mazindol competitively inhibited sDAT at the substrate analogue binding site. The results with (-)-cocaine suggest that the (-)-cocaine binding site on sDAT is distinct from that of hydroxyphenethylamine substrates, reinforcing the notion that an antagonist for (-)-cocaine binding may be developed to block (-)-cocaine binding with minimal effects on dopamine transporter activity. However, a strategy of how to antagonize drugs of abuse acting as substrate analogues is still elusive.

  14. Forecasting Three-Month Outcomes in a Laboratory School Comparison of Mixed Amphetamine Salts Extended Release (Adderall XR) and Atomoxetine (Strattera) in School-Aged Children with ADHD

    Science.gov (United States)

    Faraone, Stephen V.; Wigal, Sharon B.; Hodgkins, Paul

    2007-01-01

    Objective: Compare observed and forecasted efficacy of mixed amphetamine salts extended release (MAS-XR; Adderall) with atomoxetine (Strattera) in ADHD children. Method: The authors analyze data from a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study of children ages 6 to 12 with ADHD combined…

  15. Potential trends in Attention Deficit Hyperactivity Disorder (ADHD) drug use on a college campus: wastewater analysis of amphetamine and ritalinic acid.

    Science.gov (United States)

    Burgard, Daniel A; Fuller, Rick; Becker, Brian; Ferrell, Rebecca; Dinglasan-Panlilio, M J

    2013-04-15

    Attention Deficit Hyperactivity Disorder (ADHD) medication use is on the rise in the United States. The most widely used ADHD medications are the amphetamine-type compounds Adderall (mixed amphetamine salts) and Ritalin (methylphenidate). According to survey data ADHD medications are used as a study drug or "Smart Drug" by students without a prescription on college campuses. Survey data of non-prescribed drug use has limitations with accurate reporting and no empirical data of usage exists in the literature. This study looks for trends in the use of these drugs on a college campus among low-stress and high stress periods. The metabolites of these two drugs, amphetamine and ritalinic acid, are quantified in campus wastewater using solid phase extraction (SPE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Trends show a possible increase in amphetamine levels during periods of high stress such as midterms, the last week of classes and finals week over levels from the baseline low stress weeks such as the first week of classes. Both semesters from the 2011-12 academic year were studied and the highest increase over baseline (760%) occurred during finals week of the second semester. Ritalinic acid levels gradually climbed first semester but had no obvious periodic trend second semester. Copyright © 2013 Elsevier B.V. All rights reserved.

  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. Impulsiveness, overactivity, and poorer sustained attention improve by chronic treatment with low doses of l-amphetamine in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD).

    Science.gov (United States)

    Sagvolden, Terje

    2011-03-30

    ADHD is currently defined as a cognitive/behavioral developmental disorder where all clinical criteria are behavioral. Overactivity, impulsiveness, and inattentiveness are presently regarded as the main clinical symptoms. There is no biological marker, but there is considerable evidence to suggest that ADHD behavior is associated with poor dopaminergic and noradrenergic modulation of neuronal circuits that involve the frontal lobes. The best validated animal model of ADHD, the Spontaneously Hypertensive Rat (SHR), shows pronounced overactivity, impulsiveness, and deficient sustained attention. The primary objective of the present research was to investigate behavioral effects of a range of doses of chronic l-amphetamine on ADHD-like symptoms in the SHR. The present study tested the behavioral effects of 0.75 and 2.2 mg l-amphetamine base/kg i.p. in male SHRs and their controls, the Wistar Kyoto rat (WKY). ADHD-like behavior was tested with a visual discrimination task measuring overactivity, impulsiveness and inattentiveness. The striking impulsiveness, overactivity, and poorer sustained attention seen during baseline conditions in the SHR were improved by chronic treatment with l-amphetamine. The dose-response curves were, however, different for the different behaviors. Most significantly, the 0.75 mg/kg dose of l-amphetamine improved sustained attention without reducing overactivity and impulsiveness. The 2.2 mg/kg dose improved sustained attention as well as reduced SHR overactivity and impulsiveness. The effects of l-amphetamine to reduce the behavioral symptoms of ADHD in the SHR were maintained over the 14 days of daily dosing with no evidence of tolerance developing.

  18. Effects of amphetamine and modafinil on the sleep/wake cycle during experimental hypersomnia induced by sleep deprivation in the cat.

    Science.gov (United States)

    Lin, J S; Gervasoni, D; Hou, Y; Vanni-Mercier, G; Rambert, F; Frydman, A; Jouvet, M

    2000-03-01

    Modafinil is a newly discovered waking substance now being used in the treatment of hypersomnia and narcolepsy. We have shown previously in the cat that, unlike amphetamine, modafinil induces long-lasting wakefulness (W) without behavioral excitation and subsequent sleep rebound, and that its waking effect does not depend on endogenous catecholamines. To further characterize the awakening properties of modafinil and current psychostimulants in experimental models of hypersomnia, we examined the effect of oral administration of placebo, modafinil (5 mg kg-1) or amphetamine (1 mg kg-1) on the sleep/wake cycle and power spectral density (PSD) in cats after an 18-h water-tank sleep deprivation period. We found that the placebo had no effect on the dynamics of sleep recovery, while both modafinil and amphetamine induced suppression of cortical slow activity and a waking state lasting 6-8 h. After the amphetamine-induced waking period, both deep slow wave sleep (SWS2) and paradoxical sleep (PS) occurred in greater amounts than after placebo and the PSD during SWS was also increased. Thus, the cumulative time spent in W during a 48-h period was similar to that with placebo, indicating enhanced sleep rebound. In contrast, after the modafinil-induced W, the occurrence and evolution of SWS2 or PS, as well as the PSD during SWS, were similar to those seen with placebo during the same period, so that the total time spent in W in a 48-h period remained significantly higher than the control level, indicating no additional sleep rebound. These results indicate that modafinil is effective against somnolence and hypersomnia and does not produce a subsequent increase in sleep and suggest that the pharmacological profile of modafinil is different from that of amphetamine.

  19. The Study of the Differences of Attention Bias, Executive Functioning, and Reaction Time of Amphetamine Consumers in Comparison of Non Consumers

    Directory of Open Access Journals (Sweden)

    Nezamaldin Ghasemi

    2012-11-01

    Full Text Available Aim: Addiction to opium can be resulted to different effects. Current research designed in order to comprise if neuro-psychological functions among Amphetamine consumers and normal people. Method: Research design was causal-comparative design which performed in consumers and normal people. Research population was all opium consumers of Bahar city. Addict group included of 33 Amphetamine consumers who were referred to Baharestan addiction withdrawal center by snowball sampling. The comparison group included 39 normal people that matched with addict group with consideration of age, sex, education. All samples were studied by technical management of center and by using of perceptual diagnostic tests. Wisconsin cards, reaction time tests (simple, diagnostic, and selective and attention bias (Stroop was used. Results: the results of the research indicated that Amphetamine consumers were significantly different with normal people in consideration of error number, but there wasn’t significant difference on error in Wisconsin test. In reaction time Amphetamine consumers had least reaction time and highest number of errors, in three states. In simple trial there weren’t significant difference, but two groups were significant different in selective and diagnostic trial on time and number of errors. Also, there wasn’t significant difference on attention bias with consideration of error, but there was significant difference with consideration of time. Conclusion: on the basis of results it can be claimed Amphetamine consumption can be affected on neuro-cognitive functions. Identifying and understanding of these factors can be useful in better understanding of problem, and can be led to different therapeutic treatment.

  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. Adolescent D-amphetamine treatment in a rodent model of ADHD: Pro-cognitive effects in adolescence without an impact on cocaine cue reactivity in adulthood.

    Science.gov (United States)

    Jordan, Chloe J; Taylor, Danielle M; Dwoskin, Linda P; Kantak, Kathleen M

    2016-01-15

    Attention-deficit/hyperactivity disorder (ADHD) is comorbid with cocaine abuse. Whereas initiating ADHD medication in childhood does not alter later cocaine abuse risk, initiating medication during adolescence may increase risk. Preclinical work in the Spontaneously Hypertensive Rat (SHR) model of ADHD found that adolescent methylphenidate increased cocaine self-administration in adulthood, suggesting a need to identify alternatively efficacious medications for teens with ADHD. We examined effects of adolescent d-amphetamine treatment on strategy set shifting performance during adolescence and on cocaine self-administration and reinstatement of cocaine-seeking behavior (cue reactivity) during adulthood in male SHR, Wistar-Kyoto (inbred control), and Wistar (outbred control) rats. During the set shift phase, adolescent SHR needed more trials and had a longer latency to reach criterion, made more regressive errors and trial omissions, and exhibited slower and more variable lever press reaction times. d-Amphetamine improved performance only in SHR by increasing choice accuracy and decreasing errors and latency to criterion. In adulthood, SHR self-administered more cocaine, made more cocaine-seeking responses, and took longer to extinguish lever responding than control strains. Adolescent d-amphetamine did not alter cocaine self-administration in adult rats of any strain, but reduced cocaine seeking during the first of seven reinstatement test sessions in adult SHR. These findings highlight utility of SHR in modeling cognitive dysfunction and comorbid cocaine abuse in ADHD. Unlike methylphenidate, d-amphetamine improved several aspects of flexible learning in adolescent SHR and did not increase cocaine intake or cue reactivity in adult SHR. Thus, adolescent d-amphetamine was superior to methylphenidate in this ADHD model. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. A scoping review of home-produced heroin and amphetamine-type stimulant substitutes: implications for prevention, treatment, and policy.

    Science.gov (United States)

    Hearne, Evelyn; Grund, Jean-Paul Cornelius; Van Hout, Marie Claire; McVeigh, Jim

    2016-04-19

    Several home-produced substances such as krokodil and boltushka are prevalent in many Eastern European countries. Anecdotal reports of its use have been circulating in Germany and Norway; however, this has not been confirmed. Its use has also been reported by the media in the USA, although only one confirmed report of its use exists. Home-produced drugs are associated with high levels of morbidity and a number of complex health issues such as the spread of blood borne viruses, gangrene, and internal organ damage. The high incidence of HIV rates amongst people who inject home-produced substances is a public health concern. The resulting physical health consequences of injecting these crude substances are very severe in comparison to heroin or amphetamine acquired in black markets. Due to this fact and the increased mortality associated with these substances, professionals in the area of prevention, treatment, and policy development need to be cognisant of the presentation, harms, and the dangers associated with home-produced substances globally. This scoping review aimed to examine existing literature on the subject of home-produced heroin and amphetamine-type stimulant substitutes. The review discussed the many implications such research may have in the areas of policy and practice. Data were gathered through the use of qualitative secondary resources such as journal articles, reports, reviews, case studies, and media reports. The home production of these substances relies on the utilisation of precursor drugs such as less potent stimulants, tranquillizers, analgesics, and sedatives or natural plant ingredients. The Internet underpins the facilitation of this practice as recipes, and diverted pharmaceutical sales are available widely online, and currently, ease of access to the Internet is evident worldwide. This review highlights the necessity of prevention, education, and also harm reduction related to home-produced drugs and also recommends consistent monitoring

  3. Effects of amphetamine, diazepam and caffeine on polysomnography (EEG, EMG, EOG)-derived variables measured using telemetry in Cynomolgus monkeys.

    Science.gov (United States)

    Authier, Simon; Bassett, Leanne; Pouliot, Mylene; Rachalski, Adeline; Troncy, Eric; Paquette, Dominique; Mongrain, Valérie

    2014-01-01

    Medication-induced sleep disturbances are a major concern in drug development as a multitude of prescription drugs alter sleep patterns, often negatively. Polysomnography is used in clinical diagnostics but is also applicable to animal models. Rodent sleep architecture (nocturnal) differs from larger diurnal mammals, including humans, increasing the translational potential of non-rodent species to the clinic. This study aimed to characterize the response to pharmacological agents known to affect sleep structure and EEG activity in a non-human primate (Macaca fascicularis) using telemetry-based polysomnography. Animals were instrumented with telemetry transmitters for continuous electroencephalogram (EEG), electro-oculogram (EOG) and electromyogram (EMG) monitoring combined with video. EEG, EMG and EOG were monitored for 12 to 24h to establish baseline values, followed by administration of pharmacological agents (saline, d-amphetamine, diazepam or caffeine). Amphetamine (0.3 and 1mg/kg, by oral administration (PO)) significantly reduced total sleep time, including the duration of both non-rapid eye movement [NREM] sleep and REM sleep. It also decreased EEG activity in low frequencies (i.e., 4-6Hz) during wakefulness. Diazepam (2mg/kg, PO) did not significantly alter sleep duration, but importantly reduced EEG activity in low frequencies (approximately 2-12Hz) during wakefulness, NREM and REM sleep. Finally, caffeine (10 and 30mg/kg, PO) decreased both NREM and REM sleep duration. In addition, spectral analysis revealed important decreases in low frequency activity (i.e., 1-8Hz) during wakefulness with a parallel increase in high frequency activity (i.e., 20-50Hz) during NREM sleep. As these observations are similar to previously reported pharmacological effects in humans, results support that EEG, EOG and EMG monitoring by telemetry in Cynomolgus monkeys represents a useful non-clinical model to investigate and quantify drug-induced sleep disturbances. Copyright

  4. Efficacy and safety of psychostimulants for amphetamine and methamphetamine use disorders: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Meha Bhatt

    2016-11-01

    Full Text Available Abstract Background Amphetamine and methamphetamine use disorders are associated with severe health and social consequences. No pharmacological therapy has been approved for the treatment of these disorders. Psychostimulants can act as maintenance-like therapies for managing substance use among these patients. The aim of this study is to evaluate the literature examining the efficacy and safety of psychostimulant agents for increasing abstinence and treatment retention among patients with amphetamine and methamphetamine use disorders. Methods We searched MEDLINE, EMBASE, PsycInfo, Cochrane Central, and CINAHL from inception to August 2016. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. We conducted meta-analyses to provide a pooled summary estimate for included trials and report the review according to PRISMA guidelines. Results We identified and selected 17 studies with 1387 participants. Outcome reporting across trials was inconsistent, and the overall quality of evidence was very low due to high risk of bias and indirectness. A meta-analysis of five trials (642 participants found no effect of psychostimulants for end-of-study abstinence (odds ratio = 0.97, 95% confidence interval 0.65 to 1.45. Additionally, the pooled estimate from 14 studies (1184 participants showed no effect of psychostimulants for treatment retention (odds ratio = 1.20, 95% confidence interval = 0.91 to 1.58. The incidence of serious adverse events did not differ between intervention and placebo groups based on qualitative reports from trials. Conclusions Quantitative analyses showed no effect of psychostimulants for sustained abstinence or treatment retention. We also identified the need for more rigorous studies in this research area with clinician and patient important outcomes.

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

    International Nuclear Information System (INIS)

    Souza, Daniele Z.; Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C.; Pechansky, Flavio; Duarte, Paulina C.A.V.; De Boni, Raquel; Froehlich, Pedro E.; Limberger, Renata P.

    2011-01-01

    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 -1 , detection limits 0.5-2 ng mL -1 . → Accuracy 98-112%, precision 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 -1 (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL -1 . The detection limits were 0.5 ng mL -1 (MET), 1 ng mL -1 (MPH) and 2 ng mL -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 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.

  6. Chiral analysis of amphetamines in hair by liquid chromatography-tandem mass spectrometry: compliance-monitoring of attention deficit hyperactivity disorder (ADHD) patients under Elvanse® therapy and identification after controlled low-dose application.

    Science.gov (United States)

    Binz, Tina M; Williner, Elena; Strajhar, Petra; Dolder, Patrick C; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas; Steuer, Andrea E

    2018-02-01

    Amphetamine (AMP) is used as an illicit drug and also for the treatment of attention deficit hyperactivity disorder (ADHD). Respective drugs most often contain the enantiomer (S)-AMP as active compound or (S)-AMP is formed from the prodrug lisdexamfetamine (Elvanse®) whereas the illicit drug is usually traded as racemate ((R/S)-AMP). A differentiation between the use of the medically prescribed drug and the abuse of illicit street amphetamine is of great importance, for example in retrospective consumption monitoring by hair analysis. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the chiral separation and quantitation of (S)- and (R)-AMP in hair was developed. For this purpose, 20 mg hair was extracted and derivatized with N-(2,4-dinitro-5-fluorophenyl)-L(S)-valinamide L(S)-(DNPV) to yield amphetamine diastereomers. Baseline separation of the resulting diastereomers was achieved on a high-pressure liquid-chromatography system (HPLC) coupled to a Sciex QTRAP® 5500 linear ion trap quadrupole mass spectrometer. The method was successfully validated. Analysis of hair samples from nine Elvanse® patients revealed only (S)-AMP in eight cases; one subject showed both enantiomers indicating a (side-) consumption of street amphetamine. The analysis of the 16 amphetamine users' samples showed only racemic amphetamine. Furthermore, it could be shown in a controlled study that (S)-AMP can be detected after administration of even very low doses of lisdexamfetamine and dexamphetamine, which can be of interest in forensic toxicology and especially in drug-facilitated crime (DFC). The method now enables the retrospective compliance-monitoring of ADHD patients and the differentiation between medically prescribed intake of (S)-amphetamine and abuse of illicit street amphetamine. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Product ion mass spectra of amphetamine-type substances, designer analogues, and ketamine using ultra-performance liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Apollonio, Luigino G; Whittall, Ian R; Pianca, Dennis J; Kyd, Jennelle M; Maher, William A

    2006-01-01

    This paper describes the application of ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) technology to separate and identify amphetamine-type substances (amphetamine, methamphetamine), common and novel designer analogues (MDA, MDMA, PMA, 4-MTA, MBDB), and ketamine using Acquity UPLC/Micromass Quattro Micro API mass spectrometer instrumentation (Waters Corporation, USA). From injection of drug reference standards, it was demonstrated that these compounds can be identified by product ion mass spectra in less than 4 min total analysis time, indicating that the technological advancements associated with UPLC/MS/MS allow it to serve as a powerful analytical tool for high-throughput testing. In addition to demonstrating the separation and response of these drug compounds under the stated UPLC/MS/MS conditions, we believe the acquired product ion spectra will be a beneficial reference to laboratories interested in incorporating the use of this technology in the routine analysis of drugs of abuse.

  8. 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.

  9. Effects of 7-day continuous D-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys.

    Science.gov (United States)

    Schwienteck, Kathryn L; Banks, Matthew L

    2015-10-01

    Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice. In addition, 7-day cocaine treatment effects were also examined. Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1mg/kg/h), methylphenidate (0.032-0.32mg/kg/h), or cocaine (0.1-0.32mg/kg/h). During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. The present subchronic treatment results support the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  10. Effects of 7-day continuous d-amphetamine, methylphenidate, and cocaine treatment on choice between methamphetamine and food in male rhesus monkeys*

    Science.gov (United States)

    Schwienteck, Kathryn L.; Banks, Matthew L.

    2015-01-01

    Background Methamphetamine addiction is a significant public health problem for which no Food and Drug Administration-approved pharmacotherapies exist. Preclinical drug vs. food choice procedures have been predictive of clinical medication efficacy in the treatment of opioid and cocaine addiction. Whether preclinical choice procedures are predictive of candidate medication effects for other abused drugs, such as methamphetamine, remains unclear. The present study aim was to determine continuous 7-day treatment effects with the monoamine releaser d-amphetamine and the monoamine uptake inhibitor methylphenidate on methamphetamine vs. food choice.In addition, 7-day cocaine treatment effects were also examined. Methods Behavior was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and methamphetamine injections (0-0.32 mg/kg/injection, fixed-ratio 10 schedule) in male rhesus monkeys (n=4). Methamphetamine choice dose-effect functions were determined daily before and during 7-day periods of continuous intravenous treatment with d-amphetamine (0.01-0.1 mg/kg/h), methylphenidate (0.032-0.32 mg/kg/h), or cocaine (0.1-0.32 mg/kg/h). Results During saline treatment, increasing methamphetamine doses resulted in a corresponding increase in methamphetamine vs. food choice. Continuous 7-day treatments with d-amphetamine, methylphenidate or cocaine did not significantly attenuate methamphetamine vs. food choice up to doses that decreased rates of operant responding. However, 0.1 mg/kg/h d-amphetamine did eliminate methamphetamine choice in two monkeys. Conclusions The present subchronic treatment resultssupport the utility of preclinical methamphetamine choice to evaluate candidate medications for methamphetamine addiction. Furthermore, these results confirm and extend previous results demonstrating differential pharmacological mechanisms between cocaine choice and methamphetamine choice. PMID:26361713

  11. 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...

  12. Sexual and reproductive health risks amongst female adolescents who use amphetamine-type stimulants and sell sex: a qualitative inquiry in Yunnan, China

    OpenAIRE

    Zhang, Xudong; Kelly-Hanku, Angela; Chai, Jia-Jia; Luo, Jian; Temmerman, Marleen; Lüchters, Stanley

    2015-01-01

    Background: China, as other Southeast Asian countries, has witnessed an increased use in amphetamine-type stimulants (ATS) amongst urban youth. Amongst female adolescents who both sell sex and use ATS, risk behaviours are compounded resulting in even poorer health outcomes. However, limited knowledge exists on ATS use patterns and ATS-related risk behaviours, particularly in this context. This research aimed to improve the understanding of these issues amongst female adolescents who use ATS a...

  13. Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

    Science.gov (United States)

    Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

    2018-02-17

    Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

  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. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. 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. Copyright © 2015 The Chartered Society of Forensic Sciences. Published by Elsevier Ireland Ltd. All rights reserved.

  16. 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. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. 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.

  18. Disappearance of R/S-methamphetamine and R/S-amphetamine from human scalp hair after discontinuation of methamphetamine abuse.

    Science.gov (United States)

    Wang, Ting; Shen, Baohua; Wu, Hejian; Hu, Jingying; Xu, Huili; Shen, Min; Xiang, Ping

    2018-03-01

    Methamphetamine (MA) and amphetamine (AM) are widely abused drugs. These compounds contain a chiral center, and their enantiomers exhibit different pharmacologic, pharmacokinetic, and metabolic properties due to differences in binding affinities to their receptor sites. Until now, there was a lack of information on the decline in the concentration of drugs in hair after abstinence. A simple procedure for the chiral separation and determination of methamphetamine (MA) and its metabolite amphetamine (AM) enantiomers by LC-MS/MS in hair samples has been developed and fully validated. The LODs and LLOQs were 0.02ng/mg and 0.05ng/mg for all analytes, respectively. This method was successfully applied to both real hair specimens from chronic MA users and after the discontinuation of MA. The concentration of total MA, and total AM in fifty-eight authentic hair specimens ranged from 7.8ng/mg to 521.0ng/mg, and from 0.3ng/mg to 84.0ng/mg, respectively. Both enantiomers of MA and/or AM were detected in seven of fifty-eight authentic hair specimens. Hair specimens were from thirteen women with a known history of MA abuse, who went to a rehabilitation center and ceased consuming MA (for 4-5 months). The S-isomers of MA and AM were detected in all the 5-6cm segments. Both enantiomers of MA were detected in nine of the 5-6cm segments and the enantiomers of AM were found in only five of the nine samples. Assuming a hair growth rate of 1cm/month, the mean hair elimination half-lives of S-MA, R-MA, S-AM, and R-AM were 0.64(95% CI, 0.46-0.96), 0.58(95% CI, 0.41-0.93), 0.62(0.49-0.88), and 0.50 months (95% CI, 0.42-0.56), respectively. With the developed method, R/S-MA and R/S-AM could be detected in the hair of former drug users for approximately 4 months after abstinence. S-MA is the most commonly found analyte in hair segments and is principally used by abusers. Our results suggest that to evaluate the discontinuation of MA abuse after a 6-month period of abstinence, a 3-cm

  19. 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

  20. Modafinil alone and in combination with low dose amphetamine does not establish conditioned place preference in male Sprague-Dawley rats.

    Science.gov (United States)

    Quisenberry, Amanda J; Prisinzano, Thomas E; Baker, Lisa E

    2013-06-01

    Modafinil is a novel wake-promoting drug with FDA approval for the treatment of narcolepsy, shift work sleep disorder, and sleep apnea. It is also prescribed for many off-label uses such as ADHD and it is currently being assessed as a treatment for psychostimulant dependence. Previous research assessing the abuse liability of modafinil in animals and humans suggests it is less potent and has a low abuse potential compared to traditional psychomotor stimulants. However, modafinil has not been carefully assessed in combination with other psychostimulant drugs. The current study used an unbiased place conditioning procedure simultaneously with locomotor screening procedures to assess the combined behavioral effects of modafinil and d-amphetamine in adult male Sprague-Dawley rats. Eight 30-min conditioning trials were conducted in a 2 compartment apparatus with distinct visual and tactile cues. Drug and vehicle conditioning trials were alternated with 1 trial per day separated by 24 hr. On drug conditioning trials, rats were administered either modafinil (64 mg/kg, i.g.), d-amphetamine (0.3 or 2.0 mg/kg, s.c.), a combination of modafinil (64 mg/kg) and d-amphetamine (0.3 mg/kg), or vehicle injections. On vehicle conditioning trials, all groups received vehicle injections. Preference for either compartment was assessed by recording time spent in each compartment during a 15-min test conducted 24 hr after the last conditioning trial. Results indicated that this low oral dose of modafinil did not significantly increase locomotor activity or establish conditioned place preference (CPP). Moreover, modafinil did not significantly alter the hyperlocomotor or CPP effects of d-amphetamine. To confirm that modafinil is behaviorally active at this low oral dose, a separate assessment of horizontal and vertical activity was conducted with male Sprague-Dawley rats in an open field apparatus. Results confirmed that modafinil increased locomotor activity relative to vehicle, with

  1. 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

  2. Purification and characterisation of a new hypothalamic satiety peptide, cocaine and amphetamine regulated transcript (CART), produced in yeast.

    Science.gov (United States)

    Thim, L; Nielsen, P F; Judge, M E; Andersen, A S; Diers, I; Egel-Mitani, M; Hastrup, S

    1998-05-29

    Cocaine and amphetamine regulated transcript (CART) is a newly discovered hypothalamic peptide with a potent appetite suppressing activity following intracerebroventricular administration. When the mature rat CART sequence encoding CART(1-102) was inserted in the yeast expression plasmid three CART peptides could be purified from the fermentation broth reflecting processing at dibasic sequences. None of these corresponded to the naturally occurring CART(55-102). In order to obtain CART(55-102) the precursor Glu-Glu-Ile-Asp-CART(55-102) has been produced and CART(55-102) was generated by digestion of the precursor with dipeptidylaminopeptidase-1. All four generated CART peptides have been characterised by N-terminal amino acid sequencing and mass spectrometry. The CART peptides contain six cysteine residues and using the yeast expressed CART(62-102) the disulphide bond configuration was found to be I-III, II-V and IV-VI. When the four CART peptides were intracerebroventricularly injected in fasted mice (0.1 to 2.0 microg) they all produced a dose dependent inhibition of food intake.

  3. The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats

    Science.gov (United States)

    Andrzejewski, Matthew E.; Spencer, Robert C.; Harris, Rachel L.; Feit, Elizabeth C.; McKee, Brenda L.; Berridge, Craig W.

    2014-01-01

    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. PMID:24467844

  4. 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

    2015-01-05

    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. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. Role of calcium in phosphoinositide metabolism and inhibition of norepinephrine transport into synaptic vesicles by amphetamine analogs

    International Nuclear Information System (INIS)

    Knepper, S.M.

    1985-01-01

    Norepinephrine-(NE) and calcium ionophore A23187-stimulated phosphoinositide (PIn) metabolism in rat brain slices was studied under varying calcium conditions. Tissue was labelled with 3 H-myo-inositol and 3 H-inositol phosphates (IPn), products of PIn metabolism were measured. In the absence of media calcium the response to NE was decreased while that to A23187 was little affected A23187 can release calcium from intracellular stores. Basal and stimulated accumulation of 3 H-IPn was reversibly antagonized with EGTA by addition of calcium. Using calcium buffers, approximately 10 -7 M free calcium was required to support hydrolysis. Free intracellular calcium is maintained at approximately this level. Thus calcium is required for PIn hydrolysis but appears to play a permissive role, basal levels being sufficient to support metabolism. Conformationally-defined (rigid) and -restricted (semi-rigid) analogs of the most stable conformations of amphetamine, antiperiplanar (exo) and gauche (endo), were utilized to probe the conformational requirements of vesicular NE transport. Analogs tested were 2-aminotetralin (2AT), 3-methyltetrahydroisoquinoline, anti- and syn-9-aminobenzobicyclo[2.2.1]heptene, and endo and exo conformers of 2-aminobenzobicyclo[2.2.1]heptene and 2-aminobenzobicyclo[2.2.2]octene

  6. Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

    International Nuclear Information System (INIS)

    Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.; Gentry, W. Brooks; Owens, S. Michael

    2005-01-01

    These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, and percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats

  7. Amphetamine-induced loss of human dopamine transporter activity: An internalization-dependent and cocaine-sensitive mechanism

    Science.gov (United States)

    Saunders, Christine; Ferrer, Jasmine V.; Shi, Lei; Chen, Jiayun; Merrill, Gerald; Lamb, Maria E.; Leeb-Lundberg, L. M. Fredrik; Carvelli, Lucia; Javitch, Jonathan A.; Galli, Aurelio

    2000-01-01

    The dopamine transporter (DAT) is a target of amphetamine (AMPH) and cocaine. These psychostimulants attenuate DAT clearance efficiency, thereby increasing synaptic dopamine (DA) levels. Re-uptake rate is determined by the number of functional transporters at the cell surface as well as by their turnover rate. Here, we present evidence that DAT substrates, including AMPH and DA, cause internalization of human DAT, thereby reducing transport capacity. Acute treatment with AMPH reduced the maximal rate of [3H]DA uptake, decreased AMPH-induced currents, and significantly redistributed the immunofluorescence of an epitope-tagged DAT from the plasma membrane to the cytosol in human embryonic kidney 293 cells. Conversely, DAT inhibitors, such as cocaine, mazindol, and nomifensine, when administered with AMPH, blocked the reduction in [3H]DA uptake and the redistribution of DAT immunofluorescence to the cytosol. The reductions of [3H]DA uptake and AMPH-induced DAT internalization also were inhibited by coexpression of a dominant negative mutant of dynamin I (K44A), indicating that endocytosis modulates transport capacity, likely through a clathrin-mediated pathway. With this mechanism of regulation, acute application of AMPH would reduce DA uptake not only by direct competition for uptake, but also by reducing the available cell-surface DAT. Moreover, AMPH-induced internalization might diminish the amount of DAT available for DA efflux, thereby modulating the cytotoxic effects of elevated extracellular DA. PMID:10823899

  8. Effects of environmental enrichment and paradoxical sleep deprivation on open-field behavior of amphetamine-treated mice.

    Science.gov (United States)

    Fukushiro, Daniela Fukue; Calzavara, Mariana Bendlin; Trombin, Thaís Fernanda; Lopez, Giorgia Batlle; Abílio, Vanessa Costhek; Andersen, Monica Levy; Tufik, Sergio; Frussa-Filho, Roberto

    2007-11-23

    Environmental enrichment or paradoxical sleep deprivation (PSD) has been shown to modify some responses elicited by drugs of abuse. The aims of the present study were to examine the effects of environmental enrichment and PSD, conducted separately or in association, on open-field behavior elicited by amphetamine (AMP) in mice. Male C57BL/6 mice were randomly assigned to live in either an enriched environmental condition (EC) or a standard environmental condition (SC) for 12 months since weaning. Some of the EC and SC mice were sleep deprived for 48 h, while others were maintained in their home-cages. Immediately after PSD or home-cage stay, the animals received an ip injection of saline, 2.5 mg/kg AMP or 5.0 mg/kg AMP. Fifteen minutes later, their open-field behavior was quantified. Whereas PSD enhanced total and peripheral locomotor activity of acutely AMP-treated mice, environmental enrichment presented only a trend toward enhancement. When PSD and environmental enrichment were combined, an increase in the total and peripheral locomotion frequencies of AMP-treated animals, similar to that observed after PSD, was revealed. In addition, PSD, environmental enrichment or their combination did not modify the effects of AMP on the other open-field behavioral parameters that were analyzed. The present findings demonstrate that some (but not all) of the behavioral effects caused by AMP acute administration can be similarly and specifically enhanced by both environmental enrichment and PSD in C57BL/6 mice.

  9. Analog classroom assessment of a once-daily mixed amphetamine formulation, SLI381 (Adderall XR), in children with ADHD.

    Science.gov (United States)

    McCracken, James T; Biederman, Joseph; Greenhill, Laurence L; Swanson, James M; McGough, James J; Spencer, Thomas J; Posner, Kelly; Wigal, Sharon; Pataki, Caroly; Zhang, Yuxin; Tulloch, Simon

    2003-06-01

    This investigation was conducted primarily to assess the safety and efficacy of SLI381 (Adderall XR), developed as a once-daily treatment for children with attention-deficit/hyperactivity disorder (ADHD). Secondary objectives included examination of the time course, pharmacokinetic, and pharmacodynamic properties of SLI381. This was a randomized, double-blind, crossover study of three doses of SLI381 (10, 20, and 30 mg), placebo, and an active control (Adderall 10 mg) given once daily to 51 children with ADHD. Weekly assessments in an analog classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained every 1.5 hours over a 12-hour period. SLI381 was well tolerated. All active treatment conditions displayed significant time course effects and were superior to placebo in improving efficacy measures. Dose-dependent improvements were evident for SLI381. SLI381 20 and 30 mg and Adderall all showed rapid improvements by 1.5 hours, but only the SLI381 20- and 30-mg doses showed continued activity at 10.5 and 12 hours for classroom behavior and math test performance versus placebo. These data provide support for the benefit of this novel, once-daily amphetamine preparation in the treatment of ADHD. The longer duration of action of SLI381 has the potential to simplify psychostimulant dosing, thus reducing dose diversion and eliminating the need for in-school administration. SLI381 appears to be a useful treatment option for many children with ADHD.

  10. Fragmentation Pathways of Trifluoroacetyl Derivatives of Methamphetamine, Amphetamine, and Methylenedioxyphenyl alkylamine Designer Drugs by Gas Chromatography/Mass Spectrometry

    International Nuclear Information System (INIS)

    Kumazawa, T.; Xiao-Pen, L.; Sato, K.

    2011-01-01

    Methamphetamine (MA), amphetamine (AM), and the methylenedioxyphenyl alkylamine designer drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxy ethylamphetamine (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 spectrometry using electron ionization in positive mode. Gas chromatographic separation for TFA derivatives of all compounds was successfully resolved using an Equity-5 fused silica capillary column with a poly (5% diphenyl-95% dimethylsiloxane) stationary phase. Base peaks or prominent peaks of MA, AM, MDMA, MDEA, MBDB, MDA, and BDB appeared at m/z 154, 140, 154, 168, 168, 135, and 135, respectively. These occurred due to a-cleavage from the amide nitrogen, splitting into the TFA imine species and benzyl or methylenedioxybenzyl cations. Further prominent fragment ions at m/z 118 for MA and AM, m/z 162 for MDMA, MDEA, and MDA, and m/z 176 for MBDB and BDB were produced by cleavage of the phenylpropane or methylenedioxy propane hydrocarbon radical cation via a hydrogen rearrangement. These fragmentation pathways for the TFA derivatives of all the compounds are summarized and illustrated in this paper.

  11. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids.

    Science.gov (United States)

    Covey, Dan P; Bunner, Kendra D; Schuweiler, Douglas R; Cheer, Joseph F; Garris, Paul A

    2016-06-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  12. 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.

  13. Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1receptor activation.

    Science.gov (United States)

    Occhieppo, Victoria Belén; Marchese, Natalia Andrea; Rodríguez, Iara Diamela; Basmadjian, Osvaldo Martin; Baiardi, Gustavo; Bregonzio, Claudia

    2017-06-01

    The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT 1 -receptors (AT 1 -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT 1 -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320 g) were administered with AT 1 -R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-5) and Amph/saline (2.5 mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analysed with two-way anova followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT 1 -R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT 1 -R activation. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  14. Amphetamine elevates nucleus accumbens dopamine via an action potential-dependent mechanism that is modulated by endocannabinoids

    Science.gov (United States)

    Covey, Dan P.; Bunner, Kendra D.; Schuweiler, Douglas R.; Cheer, Joseph F.; Garris, Paul A.

    2018-01-01

    The reinforcing effects of abused drugs are mediated by their ability to elevate nucleus accumbens dopamine. Amphetamine (AMPH) was historically thought to increase dopamine by an action potential-independent, non-exocytotic type of release called efflux, involving reversal of dopamine transporter function and driven by vesicular dopamine depletion. Growing evidence suggests that AMPH also acts by an action potential-dependent mechanism. Indeed, fast-scan cyclic voltammetry demonstrates that AMPH activates dopamine transients, reward-related phasic signals generated by burst firing of dopamine neurons and dependent on intact vesicular dopamine. Not established for AMPH but indicating a shared mechanism, endocannabinoids facilitate this activation of dopamine transients by broad classes of abused drugs. Here, using fast-scan cyclic voltammetry coupled to pharmacological manipulations in awake rats, we investigated the action potential and endocannabinoid dependence of AMPH-induced elevations in nucleus accumbens dopamine. AMPH increased the frequency, amplitude and duration of transients, which were observed riding on top of slower dopamine increases. Surprisingly, silencing dopamine neuron firing abolished all AMPH-induced dopamine elevations, identifying an action potential-dependent origin. Blocking cannabinoid type 1 receptors prevented AMPH from increasing transient frequency, similar to reported effects on other abused drugs, but not from increasing transient duration and inhibiting dopamine uptake. Thus, AMPH elevates nucleus accumbens dopamine by eliciting transients via cannabinoid type 1 receptors and promoting the summation of temporally coincident transients, made more numerous, larger and wider by AMPH. Collectively, these findings are inconsistent with AMPH eliciting action potential-independent dopamine efflux and vesicular dopamine depletion, and support endocannabinoids facilitating phasic dopamine signalling as a common action in drug reinforcement

  15. 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.

  16. Role of P2X7 Receptor in an Animal Model of Mania Induced by D-Amphetamine.

    Science.gov (United States)

    Gubert, Carolina; Fries, Gabriel Rodrigo; Pfaffenseller, Bianca; Ferrari, Pâmela; Coutinho-Silva, Robson; Morrone, Fernanda Bueno; Kapczinski, Flávio; Battastini, Ana Maria Oliveira

    2016-01-01

    The objective of this study was to explore the association between the P2X7 purinergic receptor (P2X7R) and neuroinflammation using a preclinical model of acute bipolar mania. We analyzed the modulatory effects of P2X7R agonist (3'-O-(4-benzoyl)benzoyl-adenosine 5'-triphosphate, BzATP) and antagonists (brilliant blue, BBG and 3-[[5-(2,3 dichlorophenyl)-1H-tetrazol-1-yl]methyl]pyridine hydrochloride, A438079) on assessments related to behavior (locomotor activity), neuroinflammation (interleukin-1 beta, IL-1β; tumor necrosis factor alpha, TNF-α; and interleukin- 6, IL-6), oxidative stress (thiobarbituric acid reactive substances, TBARS) and neuroplasticity (brain-derived neurotrophic factor, BDNF) markers in a pharmacological model of mania induced by acute and chronic treatment with D-amphetamine (AMPH) (2 mg/kg) in mice. An apparent lack of responsiveness to AMPH was observed in terms of the locomotor activity in animals with blocked P2X7R or with genetic deletion of P2X7R in knockout (P2X7R(-/-)) mice. Likewise, P2X7R participated in the AMPH-induced increase of the proinflammatory and excitotoxic environment, as demonstrated by the reversal of IL-1β, TNF-α, and TBARS levels caused by P2X7R blocking. Our results support the hypothesis that P2X7R plays a role in the neuroinflammation induced by AMPH in a preclinical model of mania, which could explain the altered behavior. The present data suggest that P2X7R may be a therapeutic target related to the neuroinflammation reported in bipolar disorder.

  17. Adverse effects of 2,4-dichlorophenoxyacetic acid on rat cerebellar granule cell cultures were attenuated by amphetamine.

    Science.gov (United States)

    Bongiovanni, B; Ferri, A; Brusco, A; Rassetto, M; Lopez, L M; Evangelista de Duffard, A M; Duffard, R

    2011-05-01

    2,4-Dichlorophenoxyacetic acid (2,4-D), a worldwide-used herbicide, has been shown to produce a wide range of adverse effects in the health--from embryotoxicity and teratogenicity to neurotoxicity--of animals and humans. In this study, neuronal morphology and biochemical events in rat cerebellar granule cell (CGC) cultures have been analyzed to define some of the possible mechanisms involved in 2,4-D-induced cell death. For that purpose, amphetamine (AMPH) that has been shown to accelerate the recovery of several functions in animals with brain injury has been used as a pharmacologycal tool and was also investigated as a possible protecting agent. Addition of 2,4-D to CGC cultures produced a drastic decrease in cell viability, in association with an increased incidence of necrosis and apoptosis, and an increased level of reactive oxygen species, a decrease in glutathione content, and an abnormal activity of some enzymes with respect to the control group. The adverse effects of 2,4-D were partly attenuated in presence of AMPH. Some deleterious effects on several ultrastructural features of the cells, as well as the enhanced incidence of apoptosis, were partially preserved in AMPH-protected cultures as compared with those which were exposed to 2,4-D alone. The collected evidences (1) confirms the previously observed, deleterious effects of 2.4D on the same or a similar model; (2) suggests that the 2,4-D-induced apoptosis could have been mediated by or associated to an oxidative imbalance in the affected cells, and (3) shows some evidence of a protective effect of AMPH on 2,4-D-induced cell death, which could have been exerted through a reduction in the oxidative stress.

  18. 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

  19. NAAG peptidase inhibitors block cognitive deficit induced by MK-801 and motor activation induced by d-amphetamine in animal models of schizophrenia

    Science.gov (United States)

    Olszewski, R T; Janczura, K J; Ball, S R; Madore, J C; Lavin, K M; Lee, J C-M; Lee, M J; Der, E K; Hark, T J; Farago, P R; Profaci, C P; Bzdega, T; Neale, J H

    2012-01-01

    The most widely validated animal models of the positive, negative and cognitive symptoms of schizophrenia involve administration of d-amphetamine or the open channel NMDA receptor blockers, dizocilpine (MK-801), phencyclidine (PCP) and ketamine. The drug ZJ43 potently inhibits glutamate carboxypeptidase II (GCPII), an enzyme that inactivates the peptide transmitter N-acetylaspartylglutamate (NAAG) and reduces positive and negative behaviors induced by PCP in several of these models. NAAG is an agonist at the metabotropic glutamate receptor 3 (mGluR3). Polymorphisms in this receptor have been associated with expression of schizophrenia. This study aimed to determine whether two different NAAG peptidase inhibitors are effective in dopamine models, whether their efficacy was eliminated in GCPII knockout mice and whether the efficacy of these inhibitors extended to MK-801-induced cognitive deficits as assessed using the novel object recognition test. ZJ43 blocked motor activation when given before or after d-amphetamine treatment. (R,S)-2-phosphono-methylpentanedioic acid (2-PMPA), another potent NAAG peptidase inhibitor, also reduced motor activation induced by PCP or d-amphetamine. 2-PMPA was not effective in GCPII knockout mice. ZJ43 and 2-PMPA also blocked MK-801-induced deficits in novel object recognition when given before, but not after, the acquisition trial. The group II mGluR antagonist LY341495 blocked the effects of NAAG peptidase inhibition in these studies. 2-PMPA was more potent than ZJ43 in a test of NAAG peptidase inhibition in vivo. By bridging the dopamine and glutamate theories of schizophrenia with two structurally different NAAG peptidase inhibitors and demonstrating their efficacy in blocking MK-801-induced memory deficits, these data advance the concept that NAAG peptidase inhibition represents a potentially novel antipsychotic therapy. PMID:22850437

  20. Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture.

    Science.gov (United States)

    Harvey, Eric L; Baker, Lisa E

    2016-02-01

    Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to 3,4-methylenedioxymethamphetamine (MDMA) and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg MDMA, and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA + AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Dose-response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA + AMPH mixture. These findings indicate that MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-hydroxytryptamine (5-HT) receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

  1. Modafinil, d-amphetamine and placebo during 64 hours of sustained mental work. II. Effects on two nights of recovery sleep.

    Science.gov (United States)

    Buguet; Montmayeur; Pigeau; Naitoh

    1995-12-01

    Polysomnograms were obtained from 37 volunteers, before (baseline) and after (two consecutive recovery nights) a 64-h sleep deprivation, with (d-amphetamine or modafinil) or without (placebo) alerting substances. The drugs were administered at 23.00 hours during the first sleep deprivation night (after 17.5 h of wakefulness), to determine whether decrements in cognitive performance would be prevented; at 05.30 hours during the second night of sleep deprivation (after 47.5 h of wakefulness), to see whether performance would be restored; and at 15.30 hours during the third day of continuous work, to study effects on recovery sleep. The second recovery night served to verify whether drug-induced sleep disturbances on the first recovery night would carry over to a second night of sleep. Recovery sleep for the placebo group was as expected: the debt in slow-wave sleep (SWS) and REM sleep was paid back during the first recovery night, the rebound in SWS occurring mainly during the first half of the night, and that of REM sleep being distributed evenly across REM sleep episodes. Recovery sleep for the amphetamine group was also consistent with previously published work: increased sleep latency and intrasleep wakefulness, decreased total sleep time and sleep efficiency, alterations in stage shifts, Stage 1, Stage 2 and SWS, and decreased REM sleep with a longer REM sleep latency. For this group, REM sleep rebound was observed only during the second recovery night. Results for the modafinil group exhibited decreased time in bed and sleep period time, suggesting a reduced requirement for recovery sleep than for the other two groups. This group showed fewer disturbances during the first recovery night than the amphetamine group. In particular, there was no REM sleep deficit, with longer REM sleep episodes and a shorter REM latency, and the REM sleep rebound was limited to the first REM sleep episode. The difference with the amphetamine group was also marked by less NREM sleep

  2. 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. Published 2015. This article is a U.S. Government work and is in

  3. Rapid Quantitative Chiral Amphetamines Liquid Chromatography-Tandem Mass Spectrometry Method in Plasma and Oral Fluid with a Cost-effective Chiral Derivatizing Reagent

    Science.gov (United States)

    Newmeyer, Matthew N.; Concheiro, Marta; Huestis, Marilyn A.

    2014-01-01

    Methamphetamine is a widely abused psychostimulant containing a chiral center. Consumption of over-the-counter and prescription medications may yield positive amphetamines results, but chiral separation of l- and d- methamphetamine and its metabolite amphetamine can help determine whether the source was licit or illicit. We present the first LC-MS/MS method with precolumn derivatization for methamphetamine and amphetamine chiral resolution in plasma and oral fluid collected with the Oral-Eze® and Quantisal™ devices. To 0.5 mL plasma, 0.75 mL Oral-Eze, or 1 mL Quantisal specimen racemic d11-methamphetamine and amphetamine internal standards were added, followed by protein precipitation. Samples were centrifuged and supernatants loaded onto pre-conditioned Phenomenex® Strata™-XC Polymeric Strong Cation solid phase extraction columns. After washing, analytes were eluted with 5% ammonium hydroxide in methanol. The eluate was evaporated to dryness and reconstituted in water. Derivatization was performed with 1-fluoro-2,4-dinitrophenyl-5-l-alanineamide (Marfey's reagent) and heating at 45°C for 1 h. Derivatized enantiomer separations were performed under isocratic conditions (methanol:water, 60:40) with a Phenomenex® Kinetex® 2.6 μm C18 column. Analytes were identified and quantified by two MRM transitions and their ratio on a 3200 QTrap (AB Sciex) mass spectrometer in ESI negative mode. In all three matrices, the method was linear for all enantiomers from 1-500 μg/L, with imprecision and accuracy of ≤11.3% and 85.3-108%, respectively. Extraction efficiencies ranged from 67.4-117% and matrix effects from -17.0-468%, with variation always ≤19.1%. Authentic plasma and OF specimens were collected from an IRB-approved study that included controlled Vicks® VapoInhaler™ administration. The present method is sensitive, selective, economic and rapid (separations accomplished in <10 min), and improves methamphetamine result interpretation. PMID:25065924

  4. Rapid quantitative chiral amphetamines liquid chromatography-tandem mass spectrometry: method in plasma and oral fluid with a cost-effective chiral derivatizing reagent.

    Science.gov (United States)

    Newmeyer, Matthew N; Concheiro, Marta; Huestis, Marilyn A

    2014-09-05

    Methamphetamine is a widely abused psychostimulant containing a chiral center. Consumption of over-the-counter and prescription medications may yield positive amphetamines results, but chiral separation of l- and d-methamphetamine and its metabolite amphetamine can help determine whether the source was licit or illicit. We present the first LC-MS/MS method with precolumn derivatization for methamphetamine and amphetamine chiral resolution in plasma and oral fluid collected with the Oral-Eze(®) and Quantisal™ devices. To 0.5mL plasma, 0.75mL Oral-Eze, or 1mL Quantisal specimen racemic d11-methamphetamine and amphetamine internal standards were added, followed by protein precipitation. Samples were centrifuged and supernatants loaded onto pre-conditioned Phenomenex(®) Strata™-XC Polymeric Strong Cation solid phase extraction columns. After washing, analytes were eluted with 5% ammonium hydroxide in methanol. The eluate was evaporated to dryness and reconstituted in water. Derivatization was performed with 1-fluoro-2,4-dinitrophenyl-5-l-alanineamide (Marfey's reagent) and heating at 45°C for 1h. Derivatized enantiomer separations were performed under isocratic conditions (methanol:water, 60:40) with a Phenomenex(®) Kinetex(®) 2.6μm C18 column. Analytes were identified and quantified by two MRM transitions and their ratio on a 3200 QTrap (AB Sciex) mass spectrometer in ESI negative mode. In all three matrices, the method was linear for all enantiomers from 1 to 500μg/L, with imprecision and accuracy of ≤11.3% and 85.3-108%, respectively. Extraction efficiencies ranged from 67.4 to 117% and matrix effects from -17.0 to 468%, with variation always ≤19.1%. Authentic plasma and OF specimens were collected from an IRB-approved study that included controlled Vicks(®) VapoInhaler™ administration. The present method is sensitive, selective, economic and rapid (separations accomplished in <10min), and improves methamphetamine result interpretation. Published

  5. An amphetamine isomer whose efficacy and safety in humans has never been studied, β-methylphenylethylamine (BMPEA), is found in multiple dietary supplements.

    Science.gov (United States)

    Cohen, Pieter A; Bloszies, Clayton; Yee, Caleb; Gerona, Roy

    2016-01-01

    The amphetamine isomer β-methylphenylethylamine (BMPEA) was first synthesized in the early 1930s, but its efficacy and safety in humans has not been studied. Recently, the United States Food and Drug Administration (FDA) detected BMPEA in dietary supplements labelled as containing Acacia rigidula. Over a year after the FDA reported its findings, we analyzed Acacia rigidula dietary supplements to determine if BMPEA had been removed. Supplements were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry. Diluted methanolic extract from each supplement was run three times and each data set obtained was analyzed using Agilent MassHunter Qualitative Analysis. The presence of BMPEA was confirmed by accurate mass, retention time and mass spectra match against a reference standard. Quantification of BMPEA was determined using an eight-point calibration curve of spiked standard to a matrix blank. Twenty-one brands of Acacia rigidula supplements were analyzed. More than half (11/21; 52.4%) of the Acacia rigidula supplement brands contained BMPEA. The stimulant was present at quantities such that consumers following recommended maximum daily servings would consume a maximum of 93.7 mg of BMPEA per day. Consumers of Acacia rigidula supplements may be exposed to pharmacological dosages of an amphetamine isomer that lacks evidence of safety in humans. The FDA should immediately warn consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA in dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Opioid and amphetamine dependence is associated with methicillin-resistant Staphylococcus aureus (MRSA): An epidemiological register study with 73,201 Swedish in- and outpatients 1997-2013.

    Science.gov (United States)

    Dahlman, Disa; Berge, Jonas; Nilsson, Anna C; Kral, Alex H; Bjorkman, Per; Hakansson, Anders C

    2017-02-01

    While methicillin-resistant Staphylococcus aureus (MRSA) is increasing in prevalence globally, Sweden is still a low-prevalence country enabling studies on the natural MRSA spread in subpopulations unaffected by a surrounding highly infected population. Substance dependence and injection drug use have been risk factors for MRSA carriage and infection in other countries. In this retrospective, longitudinal register study, we investigated MRSA epidemiology 1997-2013 in opioid and amphetamine-dependent individuals, in comparison with alcohol-dependent subjects. Data from the national Swedish in- and outpatients registers included 73,201 individuals from 1997, 1999, 2004, 2009 and 2013. We analyzed substance use disorder and demographic predictors for MRSA using generalized estimating equations. The main finding was that both opioid (adjusted odds ratio [AOR] = 2.82; 95% confidence interval [CI] = 2.16, 3.67) and amphetamine dependence (AOR = 2.71; 95% CI = 1.70, 4.16) were significantly associated with MRSA diagnosis compared with alcohol dependence, when adjusting for age, sex and year. These findings are of value to understand the dynamics of MRSA epidemiology among substance dependent persons with presumably low socioeconomic status and potential injection drug use, and implicate repeated surveillance of MRSA among these patients.

  7. Inhibition of basal and amphetamine-stimulated extracellular signal-regulated kinase (ERK) phosphorylation in the rat forebrain by muscarinic acetylcholine M4 receptors.

    Science.gov (United States)

    He, Nan; Mao, Li-Min; Sturich, Adrian; Jin, Dao-Zhong; Wang, John Q

    2018-03-22

    The mitogen-activated protein kinase (MAPK), especially its extracellular signal-regulated kinase (ERK) subfamily, is a group of kinases enriched in the mammalian brain. While ERK is central to cell signaling and neural activities, the regulation of ERK by transmitters is poorly understood. In this study, the role of acetylcholine in the regulation of ERK was investigated in adult rat striatum in vivo. We focused on muscarinic M1 and M4 receptors, two principal muscarinic acetylcholine (mACh) receptor subtypes in the striatum. A systemic injection of the M1-perferring antagonist telenzepine did not alter ERK phosphorylation in the two subdivisions of the striatum, the caudate putamen and nucleus accumbens. Similarly, telenzepine did not affect ERK phosphorylation in the medial prefrontal cortex (mPFC), hippocampus, and cerebellum. Moreover, telenzepine had no effect on the ERK phosphorylation induced by dopamine stimulation with the psychostimulant amphetamine. In contrast to telenzepine, the M4-preferring antagonist tropicamide consistently increased ERK phosphorylation in the striatum and mPFC. This increase was rapid and transient. Tropicamide and amphetamine when coadministered at subthreshold doses induced a significant increase in ERK phosphorylation. These results demonstrate that mACh receptors exert a subtype-specific modulation of ERK in striatal and mPFC neurons. While the M1 receptor antagonist had no effect on ERK phosphorylation, M4 receptors inhibit constitutive and dopamine-stimulated ERK phosphorylation in these dopamine-innervated brain regions. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Relationship between drug discrimination and ratings of subjective effects: implications for assessing and understanding the abuse potential of D-amphetamine in humans.

    Science.gov (United States)

    Reynolds, Anna R; Bolin, B Levi; Stoops, William W; Rush, Craig R

    2013-09-01

    The discriminative and subjective effects of drugs in humans are related, but the full extent of this relationship remains to be determined. To further explore this relationship, a retrospective analysis was conducted on data from six studies completed in our laboratory that used identical procedures. The relationship between the discriminative and subjective effects of a range of doses of D-amphetamine (i.e. 2.5-15 mg) was examined using correlational analyses. Significant correlations with discrimination performance were observed on 15 of 20 items from the Drug-Effect Questionnaire across a range of qualities [e.g. Pay For (a positive effect indicative of abuse potential) and Active (a stimulant-like effect)], but the magnitude of these relationships was modest (reffects contribute to the discriminative effects of D-amphetamine and indicate that the former are a more practical means to assess the abuse potential of drugs. Although these procedures are fundamentally related in that they rely on the presence of an interoceptive drug state, they differ in the dimension(s) of the interoceptive effects that participants must quantify. The simultaneous use of drug discrimination and subjective effects may, therefore, reveal complimentary aspects of drug effects that underlie their potential for abuse.

  9. Solid-phase extraction followed by dispersive liquid-liquid microextraction for the sensitive determination of ecstasy compounds and amphetamines in biological samples

    Directory of Open Access Journals (Sweden)

    H. A. Mashayekhi

    2014-09-01

    Full Text Available A novel approach for the determination of ecstasy and amphetamines (3,4-methylenedioxymethylamphetamine (MDMA, Ecstasy, 3,4-methylenedioxyamphetamine (MDA, 3,4-methylenedioxyethylamphetamine (MDEA and 3,4-methylenedioxypropylamphetamine (MDPA in biological samples is presented. The analytes were extracted from the matrix and transferred to a small volume of a high density, water insoluble solvent using solid-phase extraction (SPE followed by dispersive liquid-liquid microextraction (DLLME. This combination not only resulted in a high enrichment factor, but also it could be used in complex matrices (biological samples. Some important extraction parameters, such as sample solution flow rate, sample pH, type and volume of extraction and disperser solvents as well as the salt addition, were studied and optimized. Under the optimized conditions, the calibration graphs were linear in the range of 0.5-500 µg L-1 and 1.0-500 µg L-1 with detection limits in the range of 0.1-0.3 µg L-1 and 0.2-0.7 µg L-1 in urine and plasma samples, respectively. The results showed that SPE-DLLME is a suitable method for the determination of ecstasy components and amphetamines in biological and water samples. DOI: http://dx.doi.org/10.4314/bcse.v28i3.3

  10. 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. © 2013 Blackwell Verlag GmbH.

  11. HIV treatment cascade among female entertainment and sex workers in Cambodia: impact of amphetamine use and an HIV prevention program.

    Science.gov (United States)

    Muth, Sokunny; Len, Aynar; Evans, Jennifer L; Phou, Maly; Chhit, Sophal; Neak, Yuthea; Ngak, Song; Stein, Ellen S; Carrico, Adam W; Maher, Lisa; Page, Kimberly

    2017-09-05

    HIV prevalence remains high in Cambodia among female entertainment and sex workers (FESW), and amphetamine-type stimulant (ATS) use significantly increases risk of infection. A successful continuum of care (CoC) is key to effective clinical care and prevention. This study aimed to describe the HIV CoC in HIV-positive FESW. We examined CoC outcomes among HIV-positive FESW participating in the Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study, being implemented in ten provinces. CIPI is a trial aimed at reducing ATS use concomitant with the SMARTgirl HIV prevention program. From 2013 to 2016, 1198 FESW ≥ 18 years old who reported multiple sex partners and/or transactional sex were recruited. We identified 88 HIV-positive women at baseline. We described linkage to care as 12-month retention and viral suppression (reported SMARTgirl membership. In the past 3 months, women reported a median of 15 sex partners, 38% reported unprotected sex, and 55% reported using ATS. Overall, 88% were receiving HIV care, 83% were on antiretroviral therapy, 39% were retained in care at 12 months, and 23% were virally suppressed. SMARTgirl membership was independently associated with fourfold greater odds of 12-month retention in care (AOR = 4.16, 95% CI 1.38, 12.56). Those at high risk for an ATS use disorder had 91% lower odds of 12-month retention in care (AOR = 0.09, 95% CI 0.01, 0.72). Viral suppression was independently associated with SMARTgirl membership, older age, reporting of STI symptoms, worse symptoms of psychological distress, and greater numbers of sex partners. This is the first study to characterize the HIV CoC in Cambodian FESW. While most women were successfully linked to HIV care, retention and viral suppression were low. Tailored programs like SMARTgirl, targeting the broader population of HIV-positive FESW as well as interventions to reduce ATS use could optimize the clinical and population health benefits of HIV treatment. Trial

  12. 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

  13. Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014

    NARCIS (Netherlands)

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

    2017-01-01

    BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by mental health concerns, including depression. Amphetamine-type-stimulants (ATS) use and homosexuality-related stigma and discrimination have been found associated with depression among MSM. OBJECTIVES: To assess the

  14. 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...

  15. 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.)

  16. Adolescent Female Cannabinoid Exposure Diminishes the Reward-Facilitating Effects of Δ9-Tetrahydrocannabinol and d-Amphetamine in the Adult Male Offspring

    Directory of Open Access Journals (Sweden)

    George Panagis

    2017-04-01

    Full Text Available Marijuana is currently the most commonly abused illicit drug. According to recent studies, cannabinoid use occurring prior to pregnancy can impact brain plasticity and behavior in future generations. The purpose of the present study was to determine whether adolescent exposure of female rats to Δ9-tetrahydrocannabinol (Δ9-THC induces transgenerational effects on the reward-facilitating effects of Δ9-THC and d-amphetamine in their adult male offspring. Female Sprague-Dawley rats received Δ9-THC (0.1 or 1 mg/kg, i.p. or vehicle during postnatal days 28–50. As adults, females were mated with drug-naïve males. We then assessed potential alterations of the Δ9-THC’s (0, 0.1, 0.5, and 1 mg/kg, i.p. and d-amphetamine’s (0, 0.1, 0.5, and 1 mg/kg, i.p. reward-modifying effects using the curve-shift variant of the intracranial self-stimulation (ICSS procedure in their adult male F1 offspring. The reward-facilitating effect of the 0.1 mg dose of Δ9-THC was abolished in the F1 offspring of females that were exposed to Δ9-THC (0.1 or 1 mg/kg, whereas the reward-attenuating effect of the 1 mg dose of Δ9-THC remained unaltered. The reward-facilitating effects of 0.5 and 1 mg of d-amphetamine were significantly decreased in the F1 offspring of females that were exposed to Δ9-THC (1 mg/kg and 0.1 or 1 mg, respectively. The present results reveal that female Δ9-THC exposure during adolescence can diminish the reward-facilitating effects of Δ9-THC and d-amphetamine in the adult male offspring. These transgenerational effects occur in the absence of in utero exposure. It is speculated that Δ9-THC exposure during female adolescence may affect neural mechanisms that are shaping reward-related behavioral responses in a subsequent generation, as indicated by the shifts in the reward-facilitating effects of commonly used and abused drugs.

  17. Rapid identification and quantification of methamphetamine and amphetamine in hair by gas chromatography/mass spectrometry coupled with micropulverized extraction, aqueous acetylation and microextraction by packed sorbent.

    Science.gov (United States)

    Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Kuwayama, Kenji; Inoue, Hiroyuki

    2009-05-01

    We developed a rapid identification and quantification method for the toxicological analysis of methamphetamine and amphetamine in human hair by gas chromatography/mass spectrometry coupled with a novel combination of micropulverized extraction, aqueous acetylation and microextraction by packed sorbent (MEPS) named MiAMi-GC/MS. A washed hair sample (1-5 mg) was micropulverized for 5 min in a 2 mL plastic tube with 250 microL of water. An anion-exchange sorbent was added to adsorb anionic interferences. After removing the residue with a membrane-filter unit, sodium carbonate and acetic anhydride was admixed in turn. Acetylation was completed in approximately 20 min at room temperature. The acetylated analytes in the reaction liquid were concentrated to an octadecylsilica sorbent packed in the needle of a syringe by a CombiPAL autosampler. Elution was carried out with 50 microL of methanol, and the entire eluate injected into a gas chromatograph using a programmable temperature vaporizing (PTV) technique. The time required for sample preparation and GC/MS analysis was approximately 1 h from a washed hair sample, and an evaporation process was not required. Ranges for quantification were 0.20-50 (ng/mg) each for methamphetamine and amphetamine using 1 mg of hair. Accuracy and relative standard deviation (RSD) were evaluated intraday and interday at three concentrations, and the results were within the limit of a guidance issued by U.S. Food and Drug Administration. For identification, full-scan mass spectra of methamphetamine and amphetamine were obtained using 5 mg of fortified hair samples at 0.2 ng/mg. The extraction device of MEPS was durable for at least 300 extractions, whereas the liner of the gas chromatograph should be replaced after 20-30 times use. The carry over was estimated to be about 1-2%. This sample-preparation method coupled with GC/MS is fast and labor-saving in comparison with conventional methods.

  18. Effect of magnesium chloride on psychomotor activity, emotional status, and acute behavioural responses to clonidine, d-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan.

    Science.gov (United States)

    Iezhitsa, Igor N; Spasov, Alexander A; Kharitonova, Maria V; Kravchenko, Maria S

    2011-01-01

    The beneficial effects of magnesium (Mg) salts on central manifestations of Mg deficiency are well known. Mg replacement therapy can be effective to prevent some of the serious depression-like and anxiety-related behaviour sequelae of Mg deficiency. However, few experimental studies have been undertaken on Mg-deficiency-induced behavioural changes. Even fewer studies have been carried out on acute behavioural responses to clonidine, D-amphetamine, arecoline, nicotine, apomorphine, and L-5-hydroxytryptophan (HTP), which might characterize possible neuromediator changes in Mg deficiency. The effects of correcting Mg deficiency by magnesium chloride (MgCl₂ · 6H₂O) and the combination of this salt with vitamin B₆, on the behavioural manifestations of Mg deficiency have never been described as well. The aims of this study were: to estimate effect of MgCl₂ · 6H₂O alone and in combination with vitamin B6 on acute behavioural responses to agonists or blockers of the main neurotransmitter systems in CNS, psychomotor activity and emotional status of rats fed with Mg-deficient diet for 49 days. In our study open field test has shown that in Mg-deficient rats locomotor activity and vertical activity, number of visiting and residence time in central squares were decreased significantly. In the elevated plus maze test, the number of visiting open arms and residence time of rats were significantly less as compared with the control group. In the forced swimming test, time immobile was significantly increased by 44.29% and time of swimming was decreased by 52.79% compared to control. In our study Mg-deficient rats were more sensitive to d-amphetamine-induced motor stereotypes. Mg deficiency antagonized 5-hydroxytryptophan-induced head-twitch response and arecoline-induced tremor. Supplement of MgCl₂ · 6H₂O with vitamin B₆ administered to a Mg-deficient rat increased the Mg level in plasma and erythrocytes. Furthermore, this increase was in relation to vitamin B

  19. Hair analysis for drugs of abuse. XIII. Effect of structural factors on incorporation of drugs into hair: the incorporation rates of amphetamine analogs.

    Science.gov (United States)

    Nakahara, Y; Kikura, R

    1996-01-01

    In order to clarify the incorporation mechanism of drugs from blood into hair, seven effects of structural factors on the incorporation rate (ICR) were studied using 32 amphetamine analogs: (1) effect of a straight chained N-alkyl group; (2) effect of benzene and furan ring at N-position; (3) effect of aliphatic and aromatic hydroxy groups; (4) effect of triple bond group at N-position; (5) effect of N-acyl group and ketone group; (6) effect of methylenedioxy and methoxy groups on benzene ring; and (7) comparison between phenyltertiarybutylamines and phenylisopropylamines. After shaving the back hair and i.p. administration of drugs to Dark-Agouti rats (5 mg/kg, 10 days, n = 3), the areas under the concentration versus time curve (AUCs) of drugs in the plasma and the concentrations in hair newly grown for 4 weeks were determined by gas chromatography-mass spectrometry. The ICRs represented by the ratios of hair concentrations to AUCs were compared with those of amphetamine (AP) and methamphetamine (MA). The ICRs of N-alkyl AP increased depending on the length of carbon branches from proton to propyl (C3 > C2 > C1 > H) at N-position. The compounds containing a benzene or furan ring at the N-position (benzphetamine, clobenzorex, norbenzphetamine, prenylamine, furfenorex, and norfurfenorex) had much higher ICRs than those of AP or MA, suggesting that a benzene or furan ring increases their ICRs. The ICRs of deprenyl, nordeprenyl, and fenproporex were significantly low, implying that triple bonds such as of a propargyl or cyano group serve as a negative factor for the ICRs. An ephedrine group (ephedrine, methylephedrine, phenylpropanolamine) showed slightly lower ICRs than the corresponding amphetamine group. However, a hydroxy group on benzene ring apparently decreased the ICRs. Methoxy and methylenedioxy groups on benzene ring distinctly increased their ICRs. The lack of basicity such as N-formyl MA, N-acetyl AP, and N-acetyl MA dramatically lowered their ICRs to

  20. Dextroamphetamine and Amphetamine

    Science.gov (United States)

    ... the extended-release capsule, you may open the capsule and sprinkle the entire contents on a teaspoonful of applesauce. Swallow this mixture right away without chewing. Do not store the applesauce and ... the contents of one capsule into more than one dose.Your doctor will ...

  1. 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.

  2. Short-term and long-term clinical evaluation of a non-amphetaminic anorexiant (mazindol) in the treatment of obesity.

    Science.gov (United States)

    Enzi, G; Baritussio, A; Marchiori, E; Crepaldi, G

    1976-01-01

    The effectiveness and tolerance of a non-amphetaminic anorexiant drug has been evaluated in a short-term and in a long-term clinical trial in simple obesity and in refractory obesity. In the short-term 'crossover' trial, a more evident effectiveness and tolerance result when the anorexiant is given in a late phase of treatment. The association of an anorexiant drug with the hypocaloric diet was seen to be effective in the treatment of so-called refractory obesity. In the evaluation of the long-term treatment it is seen that weight loss is greater and remains so farr longer periods in patients receiving anorexiant, as compared to controls. This is related to a better maintenance of a restricted calorie regimen. Mazindol did not affect the improvement of glucose tolerance and insulin secretion which follows the weight reduction.

  3. A laboratory school comparison of mixed amphetamine salts extended release (Adderall XR) and atomoxetine (Strattera) in school-aged children with attention deficit/hyperactivity disorder.

    Science.gov (United States)

    Wigal, Sharon B; McGough, James J; McCracken, James T; Biederman, Joseph; Spencer, Thomas J; Posner, Kelly L; Wigal, Tim L; Kollins, Scott H; Clark, Tanya M; Mays, David A; Zhang, Yuxin; Tulloch, Simon J

    2005-08-01

    Mixed amphetamine salts extended release (MAS XR; Adderall XR) and atomoxetine (Strattera) were compared in children 6 to 12 years old with attention deficit/hyperactivity disorder (ADHD) combined or hyperactive/impulsive type in a randomized, double-blind, multicenter, parallel-group, forced-dose-escalation laboratory school study. Primary efficacy measure was the SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham) behavioral rating scale. Changes in mean SKAMP deportment scores from baseline were significantly greater for MAS XR (n = 102) than for atomoxetine (n = 101) overall (-0.56 and -0.13, respectively; p < .0001) and at each week (p < .001). Adverse events were similar for both treatment groups. The extended time course of action and greater therapeutic efficacy of MAS XR suggests that it is more effective than atomoxetine in children with ADHD.

  4. 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). Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Anticonvulsant medications attenuate amphetamine-induced deficits in behavioral inhibition but not decision making under risk on a rat gambling task.

    Science.gov (United States)

    Tremblay, Melanie; Winstanley, Catharine A

    2016-11-01

    Impulsivity is a major component of mania in bipolar disorder (BD), and patients also show impairments in decision-making involving risk on the Iowa Gambling Task (IGT). Similar deficits are observed in some patients with temporal lobe epilepsy (TLE), and incidence of problem gambling is higher in both these populations. Anticonvulsant drugs are widely used in the treatment of epilepsy, but also as mood stabilizers and prophylaxis for the management of BD. Unfortunately, little is still known about the precise mechanisms of action underlying their efficacy, and the specific behavioral aspect targeted by these drugs. This project explored the effect of the three anticonvulsant drugs currently also used as mood stabilizers- carbamazepine, valproate and lamotrigine on aspects of decision-making using a rat analogue of the IGT, the rat Gambling Task (rGT). In this task, rats choose between four distinct, probabilistic reinforcement schedules. Sugar pellet profits are maximized by adopting a conservative strategy, avoiding tempting high-risk, high-reward options. Effects of the anticonvulsant agents were assessed on baseline performance and also in conjunction with amphetamine administration, in order to approximate a "mania-like" state. Carbamazepine appeared to slow processing speed, decreasing premature responses and increasing choice latency, whereas valproate and lamotrigine had no effect. When administered prior to amphetamine, lamotrigine was the only drug that failed to attenuate the pro-impulsive effect of the psychostimulant. Further studies looking at chronic administration of anticonvulsants may help us understand the impact of this medication class on decision-making and impulsivity in healthy rats and disease models. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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.

  7. Enhanced visual responses in the superior colliculus in an animal model of attention-deficit hyperactivity disorder and their suppression by D-amphetamine.

    Science.gov (United States)

    Clements, K M; Devonshire, I M; Reynolds, J N J; Overton, P G

    2014-08-22

    Attention-deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by overactivity, impulsiveness and attentional problems, including an increase in distractibility. A structure that is intimately linked with distractibility is the superior colliculus (SC), a midbrain sensory structure which plays a particular role in the production of eye and head movements. Although others have proposed the involvement of such diverse elements as the frontal cortex and forebrain noradrenaline in ADHD, given the role of the colliculus in distractibility and the increased distractibility in ADHD, we have proposed that distractibility in ADHD arises due to collicular sensory hyper-responsiveness. To further investigate this possibility, we recorded the extracellular activity (multi-unit (MUA) and local field potential (LFP)) in the superficial visual layers of the SC in an animal model of ADHD, the New Zealand genetically hypertensive (GH) rat, in response to wholefield light flashes. The MUA and LFP peak amplitude and summed activity within a one-second time window post-stimulus were both significantly greater in GH rats than in Wistar controls, across the full range of stimulus intensities. Given that baseline firing rate did not differ between the strains, this suggests that the signal-to-noise ratio is elevated in GH animals. D-Amphetamine reduced the peak amplitude and summed activity of the multi-unit response in Wistar animals. It also reduced the peak amplitude and summed activity of the multi-unit response in GH animals, at higher doses bringing it down to levels that were equivalent to those of Wistar animals at baseline. The present results provide convergent evidence that a collicular dysfunction (sensory hyper-responsiveness) is present in ADHD, and that it may underlie the enhanced distractibility. In addition, D-amphetamine - a widely used treatment in ADHD - may have one of its loci of therapeutic action at the level of the

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

    Science.gov (United States)

    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

    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 from a socio-ecological perspective. From September through December, 2014, 622 MSM were recruited in Hanoi and Ho Chi Minh City, Vietnam. We collected information on demographic characteristics, HIV testing behaviours, use of ATS and other recreational drugs (ever and recently), sexual sensation seeking, depressive mood, experienced and internalized stigma related to homosexuality, social involvement with other MSM, and perceptions of ATS use in MSM networks. We performed descriptive statistics to describe ATS use patterns and multivariate logistic regression to establish independent correlates of recent methamphetamine use. Nearly one-third (30.4%) had ever used ATS, including 23.6% who had used methamphetamine, 4.3% who had used amphetamine ('speed') and 20.9% who had used ecstasy. 20.1% and 11.9% had ever used methamphetamine and ecstasy, respectively, during sex. Eighteen percent of methamphetamine users were classified as engaged in high-risk use. Recent methamphetamine use (in the last 3 months) was associated with participants perceiving more methamphetamine use in their MSM network, recent sex work, and higher sexual sensation seeking scores. ATS use is relatively prevalent among MSM sampled in Vietnam's main cities. Interventions to address methamphetamine are warranted for MSM in Vietnam. Methamphetamine treatments are needed for high-risk users. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Evaluation of genetic variability in the dopamine receptor D2 in relation to behavioral inhibition and impulsivity/sensation seeking: an exploratory study with d-amphetamine in healthy participants.

    Science.gov (United States)

    Hamidovic, Ajna; Dlugos, Andrea; Skol, Andrew; Palmer, Abraham A; de Wit, Harriet

    2009-12-01

    The dopamine D2 receptor (DRD2) appears to be involved in impulsive behaviors, and particularly in behavioral inhibition. We sought to determine whether inhibition and impulsivity were related to genetic polymorphisms in the DRD2 gene (DRD2) in healthy volunteers (N = 93). Participants received placebo or d-amphetamine in random order. They performed the stop task, measuring behavioral inhibition, and rated their mood states on each session. They also completed the Zuckerman-Kuhlman Personality Questionnaire, including an Impulsivity subscale. We investigated the association between 12 single nucleotide polymorphisms (SNPs) and haplotypes in DRD2 and stop task performance in the nondrug (i.e., placebo) session and on the personality measure of impulsivity. We secondarily evaluated the DRD2 SNPs in relation to response to d-amphetamine on stop task performance and mood ratings. Mood was not related to genotypes in either the drug free condition or in response to drug. However, 2 SNPs, rs4648317 and rs12364283, and a haplotype block consisting of those SNPs, were associated with better performance on the stop task in the drug free condition and lower scores on the Impulsivity subscale. We also found that rs12364283 was associated with effects of d-amphetamine on stop task performance: d-amphetamine decreased stop reaction time (RT) in the A/A group but increased stop RT in the combined A/G + G/G genotype. Of the SNPs we evaluated, rs12364283, which has been associated with DRD2 expression, was the most significantly associated with inhibition and impulsivity. The significant relationship between DRD2 genotype and both behavioral inhibition and impulsivity suggests a possible common genetic influence on behavioral and self-report measures of impulsivity.

  10. 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.

    Science.gov (United States)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J M; Boles, Jeffrey O

    2013-06-15

    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. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 5-HT has contrasting effects in the frontal cortex, but not the hypothalamus, on changes in noradrenaline efflux induced by the monoamine releasing-agent, d-amphetamine, and the reuptake inhibitor, BTS 54 354.

    Science.gov (United States)

    Géranton, Sandrine M; Heal, David J; Stanford, S Clare

    2004-03-01

    There is extensive evidence for functional interactions between central noradrenergic and serotonergic neurones. Here, dual-probe microdialysis was used in freely-moving rats to compare the effects of 5-HT on noradrenergic transmission in the rat frontal cortex and hypothalamus. We studied the effects of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA; which depleted 5-HT stores in both the frontal cortex and the hypothalamus), on spontaneous efflux of noradrenaline and on the noradrenergic responses to d-amphetamine, and the monoamine reuptake inhibitor, BTS 54 354. pCPA pretreatment alone did not affect spontaneous noradrenaline efflux in either brain region, whether or not alpha2-autoreceptors were inactivated by administration of the alpha2-antagonist, atipamezole (1 mg/kg i.p). However, in the frontal cortex, pCPA pretreatment augmented the amplitude of, and prolonged, the noradrenergic response to local infusion of d-amphetamine (10 microM). In contrast, pCPA abolished the increase in cortical noradrenaline efflux induced by local infusion of BTS 54 354 (50 microM). In the hypothalamus, pCPA did not affect the amplitude of the response to either of these agents but did prolong the effects of d-amphetamine on noradrenaline efflux. These findings suggest that serotonergic transmission has complex effects on the noradrenergic response to drugs that increase noradrenergic transmission in the frontal cortex, but has less influence in the hypothalamus.

  12. The kappa-opioid receptor antagonist nor-BNI inhibits cocaine and amphetamine, but not cannabinoid (WIN 52212-2), abstinence-induced withdrawal in planarians: an instance of 'pharmacologic congruence'.

    Science.gov (United States)

    Raffa, Robert B; Stagliano, Gregory W; Ross, Geoffrey; Powell, Jenay A; Phillips, Austin G; Ding, Zhe; Rawls, Scott M

    2008-02-08

    The broad applicability of receptor theory to diverse species, from invertebrates to mammals, provides evidence for the evolution in complexity of pharmacologic receptor diversification and of receptor-effector signal transduction mechanisms. However, pre-mammalian species have less receptor subtype differentiation, and thus, might share signal transduction pathways to a greater extent than do mammals, a phenomenon that we term 'pharmacologic congruence'. We have demonstrated previously that the lowest species considered to have a centralized nervous system, planarians, display both abstinence-induced and antagonist-precipitated withdrawal signs, indicative of the development of physical dependence. We report here: (1) amphetamine abstinence-induced withdrawal, and (2) the attenuation of cocaine and amphetamine, but not cannabinoid agonist (WIN 52212-2), abstinence-induced withdrawal by the opioid receptor antagonist naloxone and by the selective kappa-opioid receptor subtype antagonist nor-BNI (nor-Binaltorphimine), but not by the selective mu-opioid or the delta-opioid receptor subtype antagonists CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2)) and naltrindole. These results provide evidence that the withdrawal from cocaine and amphetamine, but not cannabinoids, in planarians is mediated through a common nor-BNI-sensitive (kappa-opioid receptor-like) pathway.

  13. The efficacy and safety profile of lisdexamfetamine dimesylate, a prodrug of d-amphetamine, for the treatment of attention-deficit/hyperactivity disorder in children and adults.

    Science.gov (United States)

    Najib, Jadwiga

    2009-01-01

    Lisdexamfetamine dimesylate (LDX) is a once-daily medication approved by the US Food and Drug Administration for the management of attention-deficit/hyperactivity disorder (ADHD) in children (aged 6-12 years) and adults. This article reviews the pharmacologic and pharmacokinetic properties, clinical efficacy, and safety profile of LDX. Studies, abstracts, reviews, and consensus statements published in English were identified through computerized searches of MEDLINE (1966-August 2008) and International Pharmaceutical Abstracts (1977-August 2008) using search headings lisdexamfetamine dimesylate, attention-deficit/hyperactivity disorder, NRP 104, NRP104-201, NRP104-301, NRP104-302, NRP104-303, and stimulant. Selected information provided by the manufacturer of LDX was included, as were all pertinent clinical trials. The reference lists of identified articles were also searched for pertinent information. Relevant abstracts presented at annual professional meetings were included as well. Several studies have evaluated the pharmacokinetics of LDX in pediatric patients (6-12 years of age) and healthy adults with ADHD. LDX, a prodrug that is therapeutically inactive until metabolized in the body to dextroamphetamine (d-amphetamine), follows linear pharmacokinetics at therapeutic doses (30-70 mg). The efficacy of LDX in the treatment of ADHD was established on the basis of 1 long-term and 2 short-term controlled clinical trials in children who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, criteria for ADHD (either the combined or the hyperactive-impulsive subtype) and in 1 clinical trial with adults with ADHD. The efficacy trials in children found significant improvements in scores on the Swanson, Kotkin, Agler, M-Flynn, and Pelham deportment sub-scales, the Permanent Product Measure of Performance (Attempted and Correct), and the ADHD Rating Scale Version IV (ADHD-RS-IV) compared with placebo (all, P 60%) from baseline in the

  14. Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, 18F-fallypride in nonhuman primates using positron emission tomography.

    Science.gov (United States)

    Mukherjee, J; Yang, Z Y; Lew, R; Brown, T; Kronmal, S; Cooper, M D; Seiden, L S

    1997-09-01

    We have investigated the ability of dopamine to compete with the binding of the high affinity dopamine D2 receptor positron emission tomography (PET) radioligand, 18F-fallypride. In vitro dissociation of 18F-fallypride with dopamine in rat striatal homogenates exhibited a dissociation rate, k(off), of 1.76 x 10(-2) min(-1) while the association rate constant, k(on), was found to be 5.30 x 10(8) M(-1) min(-1). This resulted in a dissociation constant, K(D) of 33 pM for 18F-fallypride. For in vivo studies, we investigated the effects of reserpine and d-amphetamine treatment on 18F-fallypride in an attempt to study competition of endogenous dopamine with the radioligand at the receptor sites in rats and monkeys. PET experiments with 18F-fallypride in two male rhesus monkeys were carried out in a PETT VI scanner. In control experiments, rapid specific uptake of 18F-fallypride in the striata was observed (0.05-0.06% injected dose (ID)/g) while nonspecifically bound tracer cleared from other parts of the brain. Striata/cerebellum ratios for 18F-fallypride were approximately 8 at 80 min postinjection, respectively. The monkeys received various doses (0.25 to 1.50 mg/kg) of d-amphetamine (AMPH) pre- and postinjection of the radioligand. There was a decrease of specifically bound 18F-fallypride as well as evidence of an enhanced clearance of specifically bound 18F-fallypride after administering AMPH in the two monkeys. The dissociation rates, k(off), of 18F-fallypride without AMPH was doses of AMPH (0.25 mg/kg) had a reduced effect on the binding of 18F-fallypride. No effect was seen until about 30 minutes after the injection of AMPH. Studies with various doses indicated that 18F-fallypride has a maximum response at doses of 0.75-1.50 mg/kg, with an approximately 16%/hour reduction in binding. These results indicate that AMPH stimulated release of endogenous dopamine reduces the specific binding of 18F-fallypride.

  15. Simultaneous derivatization and extraction of amphetamine and methylenedioxyamphetamine in urine with headspace liquid-phase microextraction followed by gas chromatography-mass spectrometry.

    Science.gov (United States)

    Chiang, Jing-Shan; Huang, Shang-Da

    2008-03-21

    A new method is reported for the simultaneous extraction and derivatization of amphetamine (AM) and methylenedioxyamphetamine (MDA) using headspace hollow fiber protected liquid-phase microextraction (HS-HF-LPME); quantitation is by gas chromatograph-mass spectrometry in the selected ion monitoring (SIM) mode. The derivatizing reagent, pentafluorobenzaldehyde (PFBAY), was added to the extraction solvent. The analytes, volatile and basic, were released from the sample matrix into the headspace first, then extracted and derivatized in the solvent. After that, 2 microl of extract was directly injected into the GC-MS system. Parameters affecting extraction efficiency were investigated and optimized. This method showed good linearity in the concentration range investigated (50-350 ng ml(-1) for AM and 50-700 ng ml(-1) for MDA). Excellent repeatability of the extraction (RSD< or = 4%, n=5), and low limits of quantitation (0.25 ng ml(-1) for AM and 1.00 ng ml(-1) for MDA) were achieved. The feasibility of the method was demonstrated by analyzing human urine samples.

  16. Immunohistochemical localization of cocaine- and amphetamine-regulated transcript peptide (CARTp) in the brain of the pigeon (Columba livia) and zebra finch (Taeniopygia guttata).

    Science.gov (United States)

    Gutierrez-Ibanez, Cristian; Iwaniuk, Andrew N; Jensen, Megan; Graham, David J; Pogány, Ákos; Mongomery, Benjamin C; Stafford, James L; Luksch, Harald; Wylie, Douglas R

    2016-12-15

    Cocaine- and amphetamine-regulated transcript peptides (CARTp) are neuropeptides that act as neurotransmitters in the brain of vertebrates. The expression of CARTp has been characterized in teleosts, amphibians, and several mammalian species, but comparative data in reptiles and birds are nonexistent. In this study, we show the distribution of immunoreactivity against CART peptides (CARTp-ir) in the brains of two bird species: the pigeon (Columba livia) and zebra finch (Taeniopygia guttata). We found CARTp-ir cells and terminals in the brains of both, but no major differences between the two species. As in mammals, teleost fish, and amphibians, CARTp-ir terminals and cells were abundant in subpallial regions, particularly the striatum and nucleus accumbens. We also found CARTp-ir cells and terminals in the hypothalamus, and a large number of CARTp-ir terminals in the substantia nigra, ventral tegmental area, periaqueductal gray, parabrachial nucleus, and dorsal vagal complex. However, in contrast to other vertebrates, CARTp-ir was not found in the olfactory bulb. In addition there was almost no CARTp-ir in the pallium or the hippocampal formation, and little CARTp-ir in the cerebellum. The conserved expression of CARTp in the subpallium, hypothalamus, and dorsal vagal complex of birds suggests that some of the functions of CARTp, such as regulation of food intake and interactions with the social control network and mesolimbic reward system, are conserved among vertebrates. J. Comp. Neurol. 524:3747-3773, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Effects of tamoxifen on tricarboxylic acid cycle enzymes in the brain of rats submitted to an animal model of mania induced by amphetamine.

    Science.gov (United States)

    Valvassori, Samira S; Bavaresco, Daniela V; Budni, Josiane; Bobsin, Tamara S; Gonçalves, Cinara L; de Freitas, Karolina V; Streck, Emilio L; Quevedo, João

    2014-02-28

    The neurobiological basis of bipolar disorder (BD) remains unknown; nevertheless, mitochondrial dysfunction has been identified in this disorder. Inactivation of any step in the tricarboxylic acid (TCA) cycle can impair mitochondrial ATP production. There is recent evidence indicating that PKC is an important therapeutic target for bipolar disorder. Therefore, we evaluated the effects of tamoxifen (TMX--a PKC inhibitor) on the activities of enzymes in the TCA cycle of rat brains subjected to an animal model of mania induced by amphetamine. In the reversal treatment, Wistar rats were first treated with d-AMPH or saliratsne (Sal) for 14 days. Thereafter, between days 8 and 14, the rats were administered TMX or Sal. The citrate synthase, succinate dehydrogenase, and malate dehydrogenase were evaluated in the frontal cortex, hippocampus, and striatum. The d-AMPH administration inhibited TCA cycle enzymes activity in all analyzed structures, and TMX reversed d-AMPH-induced dysfunction. In addition, we observed a negative correlation between d-AMPH-induced hyperactivity and the activity of these enzymes in the rat's brain. These findings suggested that TCA cycle enzymes inhibition can be an important link for the mitochondrial dysfunction seen in BD, and TMX exert protective effects against the d-AMPH-induced TCA cycle enzymes dysfunction. © 2013 Published by Elsevier Ireland Ltd.

  18. 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.

  19. Rebound effects with long-acting amphetamine or methylphenidate stimulant medication preparations among adolescent male drivers with attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Cox, Daniel J; Moore, Melissa; Burket, Roger; Merkel, R Lawrence; Mikami, Amori Yee; Kovatchev, Boris

    2008-02-01

    This study investigated whether OROS methylphenidate (OROS MPH, Concerta) or extended-release mixed amphetamine salts (se-AMPH ER, Adderall XR) were associated with worsening of driving performance, or drug rebound, relative to placebo 16-17 hours post-ingestion. Nineteen male adolescent drivers aged 17-19 with attention-deficit/hyperactivity disorder (ADHD) were compared on a virtual reality driving simulator and an on-road drive after taking 72 mg of OROS MPH, 30 mg of se-AMPH ER, or placebo. Medication was taken at 08:00 in a randomized, double-blind, placebo-controlled, crossover study. Participants drove a simulator at 17:00, 20:00, 23:00, and 01:00, and drove their own cars over a 16-mile road course at 24:00. The main outcome measures were composite scores of driving performance. Neither OROS MPH nor se-AMPH ER was associated with significant worsening of simulator performance relative to placebo 17 hours post-ingestion in group comparisons. However, inattentive on-road driving errors were significantly more common on se-AMPH ER relative to placebo at midnight (p = 0.04), suggesting possible rebound. During both late simulator and on-road testing, driving performance variance was approximately 300% greater during the se-AMPH ER compared to the OROS MPH condition.

  20. 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.

  1. Association of the Cocaine- and Amphetamine-Regulated Transcript Prepropeptide Gene (CARTPT) rs2239670 Variant with Obesity among Kampar Health Clinic Patrons, Malaysia.

    Science.gov (United States)

    Lisa, Yeo; Sook-, Ha Fan; Yee-, How Say

    2012-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is a hypothalamic anorectic neuropeptide that controls feeding behaviour and body weight. The study objective was to investigate the association of the CART prepropeptide gene (CARTPT) rs2239670 variant with obesity and its related anthropometric indicators among patients of a Malaysian health clinic in Kampar, Perak, Malaysia. A total of 300 Malay/Peninsular Bumiputera, Chinese, and Indian subjects (115 males, 185 females; 163 non-obese, 137 obese) were recruited by convenience sampling, and anthropometric measurements, blood pressures, and pulse rate were taken. Genotyping was performed using AvaII polymerase chain reaction-restriction fragment length polymorphism. Genotyping revealed 203 (67.7%), 90 (30.0%), and 7 (2.3%) subjects with the GG, GA, and AA genotypes, respectively, with a minor allele (A) frequency of 0.17. No significant difference in the CARTPT rs2239670 genotype and allele distribution was found between obese and non-obese subjects, and logistic regression showed no association between the mutated genotypes (GA, AA) and allele (A) with obesity, even after adjusting for age, gender, and ethnicity. Furthermore, the measurements did not differ significantly between the genotypes and alleles. No significant difference in the genotype and allele distribution was found among genders, but they were significantly different among ethnicities (P = 0.030 and P = 0.019, respectively). CARTPT rs2239670 is not a predictor for obesity among the Malaysian subjects in this study.

  2. Ice in the Outback: the epidemiology of amphetamine-type stimulant-related hospital admissions and presentations to the emergency department in Hedland, Western Australia.

    Science.gov (United States)

    Monahan, Caitriona; Coleman, Mathew

    2018-03-01

    Despite research showing higher use of amphetamine-type stimulants (ATS) in rural areas, limited research has examined the epidemiology of ATS-related presentations and admissions to remote regional centres. To determine the epidemiology of ATS-related (a) Emergency Department (ED) presentations and (b) inpatient admissions over a five-year period at the Hedland Health Campus (HHC) in remote Western Australia. A retrospective review of medical records was conducted. Demographic data including gender, age and indigenous status were captured. Four hundred and eighty-two ATS-related hospital presentations were identified during the study period. The most common reason for ED presentation was mental and behavioural problems. Of those presenting, 66% were male and 69% identified as Aboriginal. ATS-related ED presentations increased seven-fold over the study period. Ninety-nine ATS-related inpatient admissions were identified during the study period. Psychotic disorder was the most common reason for admission. Males made up 75% of admissions and 53% identified as Aboriginal. This study showed a disproportionally high burden of ATS-related harm among Aboriginal people. The number of ATS-related ED presentations and inpatient admissions increased significantly over the study period.

  3. 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

    2017-06-01

    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. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. 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.

    2016-01-01

    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. PMID:26730935

  5. 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.

  6. 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. Copyright 2010 Elsevier B.V. All rights reserved.

  7. Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives.

    Science.gov (United States)

    Brindley, D N; Bowley, M

    1975-01-01

    The effects on glycerolipid synthesis of a series of compounds including many drugs were investigated in cell-free preparations and slices of rat liver. p-Chlorobenzoate, p-chlorophenoxyisobutyrate, halofenate, D-amphetamine, adrenaline, procaine and N-[2-(4-chloro-3-sulphamoylbenzoyloxy)ethyl]norfenfluramine had little inhibitory effect on any of the systems investigated. Two amphiphilic anions, clofenapate and 2-(p-chlorophenyl)-2-(m-trifluoromethylphenoxy)acetate, both inhibited glycerol phosphate acyltransferase and diacylglycerol acyltransferase at approx. 1.6 and 0.7 mm respectively. Clofenapate (1 mm) also inhibited the incorporation of glycerol into lipids by rat liver slices without altering the relative proportions of the different lipids synthesized. The amphilic amines, mepyramine, fenfluramine, norfenfluramine, hydroxyethylnorfenfluramine, N-(2-benzoyloxyethyl)norfenfluramine, cinchocaine, chlorpromazine and demethylimipramine inhibited phosphatidate phosphohydrolase by 50% at concentrations between 0.2 and 0.9 mm. The last four compounds inhibited glycerol phosphate acyltransferase by 50% at concentrations between 1 and 2.6 mm. None of the amines examined appeared to be an effective inhibitor of diacylglycerol acyltransferase. Norfenfluramine, hydroxyethylnorfenfluramine and N-(2-benzoyloxyethyl)norfenfluramine produced less inhibition of glycerol incorporation into total lipids than was observed with equimolar clofenapate. The major effect of these amines in liver slices was to inhibit triacylglycerol and phosphatidylcholine synthesis and to produce a marked accumulation of phosphatidate. The results are discussed in terms of the control of glycerolipid synthesis. They partly explain the observed effects of the various drugs on lipid metabolism. The possible use of these compounds as biochemical tools with which to investigate the reactions of glycerolipid synthesis is considered. PMID:1200988

  8. Developmental Exposure to PCBs and/or MeHg: Effects on a Differential Reinforcement of Low Rates (DRL) Operant Task Before and After Amphetamine Drug Challenge

    Science.gov (United States)

    Sable, Helen J. K.; Eubig, Paul A.; Powers, Brian E.; Wang, Victor C.; Schantz, Susan L.

    2009-01-01

    The current study assessed the effects of developmental PCB and/or MeHg exposure on an operant task of timing and inhibitory control and determined if amphetamine (AMPH) drug challenges differentially affected performance. Long-Evans rats were exposed to corn oil (control), PCBs alone (1 or 3 mg/kg), MeHg alone (1.5 or 4.5 ppm), the low combination (1 mg/kg PCBs + 1.5 ppm MeHg), or the high combination (3 mg/kg PCBs + 4.5 ppm MeHg) throughout gestation and lactation. An environmentally relevant, formulated PCB mixture was used. Male and female offspring were trained to asymptotic performance on a differential reinforcement of low rates (DRL) operant task as adults. PCB-exposed groups had a lower ratio of reinforced to non-reinforced responses than controls. Groups exposed to MeHg alone were not impaired and the deficits observed in PCB-exposed groups were not seen when PCBs were co-administered with MeHg. AMPH was less disruptive to responding in males receiving PCBs alone, MeHg alone, and 1.0 mg/kg PCB + 1.5 ppm MeHg. Paradoxically, the disruption in responding by AMPH in males given 3.0 mg/kg PCB + 4.5 ppm MeHg did not differ from controls. Exposed females from all treatment groups did not differ from controls in their AMPH response. Overall, the findings suggest that developmental exposure to PCBs can decrease DRL performance. Co-exposure to MeHg seemed to mitigate the detrimental effects of PCBs on performance. The finding that the disruptive effects of AMPH on DRL performance were lessened in some groups of exposed males suggests that alterations in dopaminergic functioning may have a role in behavioral changes seen after perinatal PCB and MeHg exposure. PMID:19344642

  9. Sexual and reproductive health risks amongst female adolescents who use amphetamine-type stimulants and sell sex: a qualitative inquiry in Yunnan, China.

    Science.gov (United States)

    Zhang, Xu-Dong; Kelly-Hanku, Angela; Chai, Jia-Jia; Luo, Jian; Temmerman, Marleen; Luchters, Stanley

    2015-10-16

    China, as other Southeast Asian countries, has witnessed an increased use in amphetamine-type stimulants (ATS) amongst urban youth. Amongst female adolescents who both sell sex and use ATS, risk behaviours are compounded resulting in even poorer health outcomes. However, limited knowledge exists on ATS use patterns and ATS-related risk behaviours, particularly in this context. This research aimed to improve the understanding of these issues amongst female adolescents who use ATS and sell sex, and to inform future programming. This study utilised monthly focus group discussions (four in total) with the same study participants in Yunnan, China. From within a drug-treatment programme, female adolescents who reported both a history of drug use and selling sex were purposively enrolled in the study. Participating adolescent females were aged 17-19 years and were all internal-migrants with low literacy. All reported polydrug use (mainly methamphetamine and heroin, whereas ecstasy and ketamine have been infrequently employed). Being less informed about risks of drug use and lack of sexual and reproductive health knowledge seemed to contribute to problematic drug use, rough and prolonged sexual intercourse, inconsistent condom use and ineffective contraceptive practice. For their income, participants largely relied on selling sex, which was frequently coupled with drug sharing services to clients. However, despite the practices, women did not self-identify as sex workers, and therefore did not think that existing intervention services targeting female sex workers were relevant to them. Moreover, criminalization and stigmatisation of drug use and selling sex impeded their access to care services. Current harm reduction and HIV/sexually transmitted infection (STI) prevention services are unlikely to address the demand of female adolescents engaged in drug use and commercial sex. Our findings highlight that a comprehensive and coordinated harm reduction and sexual and

  10. Effects of gender on locomotor sensitivity to amphetamine, body weight, and fat mass in regulator of G protein signaling 9 (RGS9) knockout mice.

    Science.gov (United States)

    Walker, Paul D; Jarosz, Patricia A; Bouhamdan, Mohamad; MacKenzie, Robert G

    2015-01-01

    Regulator of G-protein signaling (RGS) protein 9-2 is enriched in the striatum where it modulates dopamine and opioid receptor-mediated signaling. RGS9 knockout (KO) mice show increased psychostimulant-induced behavioral sensitization, as well as exhibit higher body weights and greater fat accumulation compared to wild-type (WT) littermates. In the present study, we found gender influences on each of these phenotypic characteristics. Female RGS9 KO mice exhibited greater locomotor sensitization to amphetamine (1.0mg/kg) treatment as compared to male RGS9 KO mice. Male RGS9 KO mice showed increased body weights as compared to male WT littermates, while no such differences were detected in female mice. Quantitative magnetic resonance showed that male RGS9 KO mice accumulated greater fat mass vs. WT littermates at 5months of age. Such observations could not be explained by increased caloric consumption since male and female RGS9 KO mice demonstrated equivalent daily food intake as compared to their respective WT littermates. Although indirect calorimetry methods found decreased oxygen consumption and carbon dioxide production during the 12-hour dark phase in male RGS9 KO vs. WT mice which are indicative of less energy expenditure, male RGS9 KO mice exhibited lower levels of locomotor activity during this period. Genotype had no effect on metabolic activities when KO and WT groups were compared under fasting vs. feeding treatments. In summary, these results highlight the importance of factoring gender into the experimental design since many studies conducted in RGS9 KO mice utilize locomotor activity as a measured outcome. Copyright © 2014. Published by Elsevier Inc.

  11. Dynamics of cocaine- and amphetamine-regulated transcript containing cell changes in the adrenal glands of two kidney, one clip rats.

    Science.gov (United States)

    Kasacka, Irena; Piotrowska, Zaneta; Janiuk, Izabela; Zbucki, Robert

    2014-10-01

    Taking into consideration the homeostatic disorders resulting from renal hypertension and the essential role of cocaine- and amphetamine-regulated transcript (CART) in maintaining homeostasis by regulating many functions of the body, the question arises as to what extent the renovascular hypertension affects the morphology and dynamics of changes of CART-containing cells in the adrenal glands. The aim of the present study was to examine the distribution, morphology, and dynamics of changes of CART-containing cells in the adrenal glands of "two kidney, one clip" (2K1C) renovascular hypertension model in rats. The studies were carried out on the adrenal glands of rats after 3, 14, 28, 42, and 91 days from the renal artery clipping procedure. To identify neuroendocrine cells, immunohistochemical reaction was performed with the use of a specific antibody against CART. It was revealed that renovascular hypertension causes changes in the endocrine cells containing CART in the adrenal glands of rats. The changes observed in the endocrine cells depend on the time when the rats with experimentally induced hypertension were examined. In the first period of hypertension, the number and immunoreactivity of CART-containing cells were decreased, while from the 28-day test, it significantly increased, as compared to the control rats. CART is relevant to the regulation of homeostasis in the cardiovascular system and seems to be involved in renovascular hypertension. The results of the present work open the possibility of new therapeutic perspectives for the treatment of arterial hypertension, since CART function is involved in their pathophysiology. © 2014 by the Society for Experimental Biology and Medicine.

  12. 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

  13. 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

    International Nuclear Information System (INIS)

    Madireddy, Sri Bharat; Bodeddula, Vanaja Reddy; Mansani, Sravan Kumar; Wells, Martha J.M.; Boles, Jeffrey O.

    2013-01-01

    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

  14. 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.

  15. The mixed amphetamine salt extended release (Adderall XR, Max-XR) as an adjunctive to SSRIS or SNRIS in the treatment of adult ADHD patients with comorbid partially responsive generalized anxiety: an open-label study.

    Science.gov (United States)

    Gabriel, Adel

    2010-06-01

    To examine the changes in partially responsive anxiety symptoms utilizing adjunctive treatment with the mixed amphetamine salt extended release (Adderall XR, MAX-XR) in the treatment of adult ADHD patients, with comorbid refractory anxiety. Consenting adult patients (n = 32) with confirmed diagnosis of generalized anxiety (GA) and comorbid (ADHD) participated in this open-label study. All patients had significant comorbid anxiety symptoms (HAM-A > 7) and failed to respond to 8-week trials of Serotonin Reuptake Inhibitors (SSRIs) or Norepinephrine Reuptake inhibitors (SNRIs). All patients were treated with the "Mixed Amphetamine salts Extended Release Adderall XR, (MAS-XR), as adjunctive to SSRIs or to SNRIs and were followed for at least 12 weeks. The primary effectiveness measure was the Clinical Global Impression severity subscale (CGI-S). Other scales included the Hamilton Anxiety Scale (HAM-A), the adult ADHD Self-Report Scale (ASRS-v1.1) symptom checklist, and Sheehan's disability scale. Baseline measures prior to the treatment with MAS-XR were compared to those at 4, 8, and at 12 weeks of treatment. Monitoring for pulse, blood pressure, and weight changes was carried out at baseline and at end point. All patients completed this open-label trial. There was significant and robust resolution of symptoms of all effectiveness measures, including the symptoms of anxiety, as shown by changes from baseline in HAM-A, ASRS-v1.1, and CGI at 8 weeks. Also there was significant reduction in the disability score at 12 weeks. Patients tolerated the treatment, and there were no significant cardiovascular changes at 12 weeks. There was decrease in mean weight at 12 weeks by 2.2 kg (P < .001). Mixed amphetamine salts MAS-XR can be used in adult patients with ADHD and comorbid anxiety symptoms. Larger controlled studies are needed to support the effectiveness of mixed amphetamine salts in patients with comorbid anxiety symptoms. Treatments need to include the targeting of the

  16. A demonstration of the use of ultra-performance liquid chromatography-mass spectrometry [UPLC/MS] in the determination of amphetamine-type substances and ketamine for forensic and toxicological analysis.

    Science.gov (United States)

    Apollonio, Luigino G; Pianca, Dennis J; Whittall, Ian R; Maher, William A; Kyd, Jennelle M

    2006-05-19

    We have recently seen the emergence of ultra-performance liquid chromatography (UPLC) coupled to mass spectrometry as an alternative to traditional high-performance liquid chromatography techniques. The strengths of UPLC technology promote the ability to separate and identify drug compounds with significant gains in resolution and sensitivity and marked reductions in the overall time of analysis. As increased throughput is the desire of the practical toxicology laboratory, the aim of this study was to trial commercially available technology by assessment of the separation of several commonly encountered amphetamine-type substances. From injection of a poly-drug reference standard and whole blood extract, we successfully separated and identified amphetamine, methamphetamine, ephedrine, pseudoephedrine, phentermine, MDA, MDMA, MDEA and ketamine in less than 3 min using the Acquity UPLC-Micromass Quattro Micro API MS instrumentation (Waters Corporation, USA). In addition to this significant reduction in overall run time, all peaks exhibited acceptable resolution using selected ion recording (SIR), with analysis indicating the capability to separate 5-11 peaks in 1.75 min using the current system parameters. From this introductory data, it is therefore indicated that the technological advancements defining ultra-performance liquid chromatography will allow it to serve as a powerful analytical tool for rapid throughput analysis.

  17. 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.

  18. Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

    Science.gov (United States)

    Renard, Justine; Loureiro, Michael; Rosen, Laura G; Zunder, Jordan; de Oliveira, Cleusa; Schmid, Susanne; Rushlow, Walter J; Laviolette, Steven R

    2016-05-04

    Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes. Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses. However, the neuronal and molecular mechanisms through which CBD may exert these effects are entirely unknown. We used amphetamine (AMPH)-induced sensitization and sensorimotor gating in rats, two preclinical procedures relevant to schizophrenia-related psychopathology, combined with in vivo single-unit neuronal electrophysiology recordings in the ventral tegmental area, and molecular analyses to characterize the actions of CBD directly in the nucleus accumbens shell (NASh), a brain region that is the current target of most effective antipsychotics. We demonstrate that Intra-NASh CBD attenuates AMPH-induced sensitization, both in terms of DAergic neuronal activity measured in the ventral tegmental area and psychotomimetic behavioral analyses. We further report that CBD controls downstream phosphorylation of the mTOR/p70S6 kinase signaling pathways directly within the NASh. Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology. The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia. However, the mechanisms by which CBD may produce

  19. Chiral separations of cathinone and amphetamine-derivatives: Comparative study between capillary electrochromatography, supercritical fluid chromatography and three liquid chromatographic modes.

    Science.gov (United States)

    Albals, Dima; Heyden, Yvan Vander; Schmid, Martin G; Chankvetadze, Bezhan; Mangelings, Debby

    2016-03-20

    The screening part of an earlier defined chiral separation strategy in capillary electrochromatography (CEC) was used for the separation of ten cathinone- and amphetamine derivatives. They were analyzed using 4 polysaccharide-based chiral stationary phases (CSPs), containing cellulose tris(3,5-dimethylphenylcarbamate) (ODRH), amylose tris(3,5-dimethylphenylcarbamate) (ADH), amylose tris(5-chloro-2-methylphenylcarbamate) (LA2), and cellulose tris(4-chloro-3-methylphenylcarbamate) (LC4) as chiral selectors. After applying the screening to each compound, ADH and LC4 showed the highest success rate. In a second part of the study, a comparison between CEC and other analytical techniques used for chiral separations i.e., supercritical fluid chromatography (SFC), polar organic solvent chromatography (POSC), reversed-phase (RPLC) and normal-phase liquid chromatography (NPLC), was made. For this purpose, earlier defined screening approaches for each technique were applied to separate the 10 test substances. This allowed an overall comparison of the success rates of the screening steps of the 5 techniques for these compounds. The results showed that CEC had a similar enantioselectivity rate as NPLC and RPLC, producing the highest number of separations (9 out of 10 racemates). SFC resolved 7 compounds, while POSC gave only 2 separations. On the other hand, the baseline separation success rates for NPLC and RPLC was better than for CEC. For a second comparison, the same chiral stationary phases as in the CEC screening were also tested with all techniques at their specific screening conditions, which allowed a direct comparison of the performance of CEC versus the same CSPs in the other techniques. This comparison revealed that RPLC was able to separate all tested compounds, and also produced the highest number of baseline separations on the CSP that were used in the CEC screening step. CEC and NPLC showed the same success rate: nine out of ten substances were separated. When

  20. Neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) in winter skate (Raja ocellata): cDNA cloning, tissue distribution and mRNA expression responses to fasting.

    Science.gov (United States)

    MacDonald, Erin; Volkoff, Hélène

    2009-04-01

    cDNAs encoding for neuropeptide Y (NPY), cocaine- and amphetamine-regulated transcript (CART) and cholecystokinin (CCK) were cloned in an elasmobranch fish, the winter skate. mRNA tissue distribution was examined for the three peptides as well as the effects of two weeks of fasting on their expression. Skate NPY, CART and CCK sequences display similarities with sequences for teleost fish but in general the degree of identity is relatively low (50%). All three peptides are present in brain and in several peripheral tissues, including gut and gonads. Within the brain, the three peptides are expressed in the hypothalamus, telencephalon, optic tectum and cerebellum. Two weeks of fasting induced an increase in telencephalon NPY and an increase in CCK in the gut but had no effects on hypothalamic NPY, CART and CCK, or on telencephalon CART. Our results provide basis for further investigation into the regulation of feeding in winter skate.

  1. SLI381 (Adderall XR), a two-component, extended-release formulation of mixed amphetamine salts: bioavailability of three test formulations and comparison of fasted, fed, and sprinkled administration.

    Science.gov (United States)

    Tulloch, Simon J; Zhang, Yuxin; McLean, Angus; Wolf, Kathleen N

    2002-11-01

    To assess the bioavailability of three test formulations of a single dose of extended-release Adderall 20-mg capsules compared with two doses of immediate-release Adderall 10-mg tablets, and to assess the bioequivalence of a single 30-mg dose of the chosen extended-release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food. Randomized, open-label, crossover study. Clinical research unit. Forty-one healthy adults. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended-release Adderall 20 mg, and two 10-mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high-fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce. The 20-mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d- and l-amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30-mg dose of SLI381 showed no significant differences in rate and extent of absorption of d- and l-amphetamine for fasted or sprinkled conditions compared with the high-fat meal condition. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.

  2. Enantiomeric separation and quantitation of (+/-)-amphetamine, (+/-)-methamphetamine, (+/-)-MDA, (+/-)-MDMA, and (+/-)-MDEA in urine specimens by GC-EI-MS after derivatization with (R)-(-)- or (S)-(+)-alpha-methoxy-alpha-(trifluoromethy)phenylacetyl chloride (MTPA).

    Science.gov (United States)

    Paul, Buddha D; Jemionek, John; Lesser, David; Jacobs, Aaron; Searles, Douglas A

    2004-09-01

    In drug testing, the presence of methamphetamine in urine is generally confirmed by a gas chromatography-mass spectrometry (GC-MS) method. Derivatization of the compound to a perfluoroalkylamide, prior to confirmation, typically yields better chromatographic separation. Once methamphetamine is detected, a second GC-MS test is necessary to distinguish positive results from the use of over-the-counter medication, Vicks inhaler, or from use of a prescription drug, selegiline (Deprenyl). R-(-)-Methamphetamine is the urinary product from legitimate use of these medications. The second GC-MS test is to confirm illicit use of (S)-(+)-methamphetamine. In the procedure, the two methamphetamine isomers are changed to the chromatographically separable diastereomers by a chiral derivatizing agent, (S)-(-)-trifluoroacetylprolyl chloride (TPC). But the method has inherent limitations. Racemization of the reagent produces mixed diastereomers even from pure (S)-(+)-methamphetamine. Instead of using TPC, we utilized (R)-(-)-alpha-methoxy-alpha-(trifluoromethyl)phenylacetyl chloride (MTPA) to prepare the amides of diastereomers of methamphetamine. No racemization was observed with this reagent. The method was extended to resolve GC peaks of (R)-(-)- and (S)-(+)-isomers of amphetamine, 3,4-methylenedioxyamphetamine (MDA), N-methyl-MDA (MDMA), and N-ethyl-MDA (MDEA). Three ions from the drug and two ions from the deuterated internal standard were monitored to characterize and quantitate the drugs. For MDEA, only one ion was used. The quantitation was linear over 25 to 5000 ng/mL for MDEA and 25 to 10,000 ng/mL for all other drugs. Correlation coefficients were > 0.996. Precision calculated as the coefficient of variation at the calibrator concentration of 500 ng/mL was within +/- 11% for all drugs. The method was applied to test 43 urine specimens. In 91% of the methamphetamine-positive specimens, only the (S)-(+)-isomer was detected. In all MDMA-positive specimens, the concentrations

  3. Enhanced effects of amphetamine but reduced effects of the hallucinogen, 5-MeO-DMT, on locomotor activity in 5-HT1A receptor knockout mice: Implications for schizophrenia

    Science.gov (United States)

    van den Buuse, Maarten; Ruimschotel, Emma; Martin, Sally; Risbrough, Victoria B.; Halberstadt, Adam L.

    2012-01-01

    Serotonin-1A (5-HT1A) receptors may play a role in schizophrenia and the effects of certain antipsychotic drugs. However, the mechanism of interaction of 5-HT1A receptors with brain systems involved in schizophrenia, remains unclear. Here we show that 5-HT1A 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-HT1A 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 D1 or D2 receptors which could explain the behavioural changes observed in 5-HT1A 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-HT1A receptors may play an important role in hallucinations and to modulate dopaminergic activity in the brain. PMID:21501627

  4. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. 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.

  6. Why does the Y326I mutant of monoamine oxidase B decompose an endogenous amphetamine at a slower rate than the wild type enzyme? Reaction step elucidated by multiscale molecular simulations.

    Science.gov (United States)

    Pregeljc, Domen; Jug, Urška; Mavri, Janez; Stare, Jernej

    2018-02-07

    This work investigates the Y326I point mutation effect on the kinetics of oxidative deamination of phenylethylamine (PEA) catalyzed by the monoamine oxidase B (MAO B) enzyme. PEA is a neuromodulator capable of affecting the plasticity of the brain and is responsible for the mood enhancing effect caused by physical exercise. Due to a similar functionality, PEA is often regarded as an endogenous amphetamine. The rate limiting step of the deamination was simulated at the multiscale level, employing the Empirical Valence Bond approach for the quantum treatment of the involved valence states, whereas the environment (solvated protein) was represented with a classical force field. A comparison of the reaction free energy profiles delivered by simulation of the reaction in the wild type MAO B and its Y326I mutant yields an increase in the barrier by 1.06 kcal mol -1 upon mutation, corresponding to a roughly 6-fold decrease in the reaction rate. This is in excellent agreement with the experimental kinetic studies. Inspection of simulation trajectories reveals possible sources of the point mutation effect, namely vanishing favorable electrostatic interactions between PEA and a Tyr326 side chain and an increased amount of water molecules at the active site due to the replacement of tyrosine by a less spacious isoleucine residue, thereby increasing the dielectric shielding of the catalytic environment provided by the enzyme.

  7. Amphetamine-Type-Stimulants (ATS) Use and Homosexuality-Related Enacted Stigma Are Associated With Depression Among Men Who Have Sex With Men (MSM) in Two Major Cities in Vietnam in 2014.

    Science.gov (United States)

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

    2017-09-19

    Men who have sex with men (MSM) are disproportionately affected by mental health concerns, including depression. Amphetamine-type-stimulants (ATS) use and homosexuality-related stigma and discrimination have been found associated with depression among MSM. To assess the prevalence of depression and its associations with ATS use and homosexuality-related stigma and discrimination among MSM in Vietnam. 622 MSM were conveniently recruited in Hanoi and Ho Chi Minh city, Vietnam, from September to December 2014. We collected information on demographic characteristics, ATS, alcohol and other drug use, sexual behaviors, homosexuality-related and discrimination stigma, and sexual sensation-seeking. Depression and suicidal thoughts were assessed by the Patient Health Questionnaire (PHQ-9). We assessed associations of depression with ATS use and homosexuality-related stigma and discrimination using logistic regression. Of 622 sampled MSM, 11.3% were classified as having major depression, 9.8% reported any suicidal thoughts in the last two weeks, 30.4% ever had used any ATS, 88.8% ever ad drank alcohol and 21.5% had ever used any other drugs. In multivariate analysis, depression was significantly associated with ATS use (Adjusted Odds Ratio [AOR: 2.20; (95% Confidence Interval (CI): 1.32-3.67], younger age of sexual debut with another man (AOR: 0.09; 95% CI: 0.02-0.50), and greater enacted homosexuality-related stigma (AOR: 1.97; 95% CI: 1.19-3.26). We found a moderate prevalence of depression among sampled MSM, which was associated with ATS use and enacted homosexuality-related stigma. We recommend integrating assessment and interventions regarding depression and methamphetamine use into gay-friendly, culturally adapted holistic HIV prevention for MSM in Vietnam.

  8. Protocol of a cluster randomised stepped-wedge trial of behavioural interventions targeting amphetamine-type stimulant use and sexual risk among female entertainment and sex workers in Cambodia.

    Science.gov (United States)

    Page, Kimberly; Stein, Ellen S; Carrico, Adam W; Evans, Jennifer L; Sokunny, Muth; Nil, Ean; Ngak, Song; Sophal, Chhit; McCulloch, Charles; Maher, Lisa

    2016-05-09

    HIV risk among female entertainment and sex workers (FESW) remains high and use of amphetamine-type stimulants (ATS) significantly increases this risk. We designed a cluster randomised stepped wedge trial (The Cambodia Integrated HIV and Drug Prevention Implementation (CIPI) study) to test sequentially delivered behavioural interventions targeting ATS use. The trial combines a 12-week Conditional Cash Transfer (CCT) intervention with 4 weeks of cognitive-behavioural group aftercare (AC) among FESW who use ATS. The primary goal is to reduce ATS use and unprotected sex among FESW. The CCT+AC intervention is being implemented in 10 provinces where order of delivery was randomised. Outcome assessments (OEs) including biomarkers and self-reported measures of recent sexual and drug use behaviours are conducted prior to implementation, and at three 6-month intervals after completion. Consultation with multiple groups and stakeholders on implementation factors facilitated acceptance and operationalisation of the trial. Statistical power and sample size calculations were based on expected changes in ATS use and unprotected sex at the population level as well as within subjects. Ethical approvals were granted by the Cambodia National Ethics Committee; University of New Mexico; University of California, San Francisco; and FHI360. The trial is registered with ClinicalTrials.gov. Dissemination of process indicators during the multiyear trial is carried out through annual in-country Stakeholder Meetings. Provincial 'Close-Out' forums are held at the conclusion of data collection in each province. When analysis is completed, dissemination meetings will be held in Cambodia with stakeholders, including community-based discussion sessions, policy briefs and results published and presented in the HIV prevention scientific journals and conferences. CIPI is the first trial of an intervention to reduce ATS use and HIV risk among FESW in Cambodia. Will inform both CCT+AC implementation

  9. SHP465 Mixed Amphetamine Salts in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: Results of a Randomized, Double-Blind Placebo-Controlled Study.

    Science.gov (United States)

    Brams, Matthew; Childress, Ann C; Greenbaum, Michael; Yu, Ming; Yan, Brian; Jaffee, Margo; Robertson, Brigitte

    2018-02-01

    The aim of this study was to evaluate the efficacy, safety, and tolerability of SHP465 mixed amphetamine salts (MAS) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). This randomized, double-blind dose-optimization study enrolled children and adolescents (6-17 years) meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision ADHD criteria and having baseline ADHD Rating Scale IV (ADHD-RS-IV) total scores ≥28. Participants were randomized 1:1 to placebo or dose-optimized SHP465 MAS (12.5-25 mg) for 4 weeks. Total score change (baseline to week 4) on the ADHD-RS-IV (primary endpoint) and the Clinical Global Impressions-Improvement (CGI-I) scale score at week 4 (key secondary endpoint) were assessed using linear mixed-effects models for repeated measures. Safety and tolerability assessments (secondary endpoints) included treatment-emergent adverse events (TEAEs) and vital sign changes. Of 264 randomized participants (placebo, n = 132; SHP465 MAS, n = 132), 234 (placebo, n = 118; SHP465 MAS, n = 116) completed the study. The least squares mean (95% confidence interval) treatment difference significantly favored SHP465 MAS over placebo for ADHD-RS-IV total score change from baseline to week 4 (-9.9 [-13.0, -6.8]; p serious TEAEs were reported. TEAEs reported at a frequency of ≥5% and ≥2 times the placebo rate were decreased appetite, insomnia, irritability, nausea, and decreased weight. Mean ± standard deviation increases (baseline to final on-treatment assessment) were higher with SHP465 MAS than placebo for pulse (5.7 ± 11.78 vs. 0.7 ± 10.79), systolic blood pressure (3.8 ± 9.15 vs. 2.1 ± 8.72), and diastolic blood pressure (4.0 ± 8.23 vs. 0.5 ± 7.45). SHP465 MAS demonstrated superiority over placebo in improving ADHD symptoms and global functioning in children and adolescents with ADHD. The safety and tolerability profile of SHP465 MAS was

  10. Methamphetamine and the expanding complications of amphetamines.

    OpenAIRE

    Albertson, T E; Derlet, R W; Van Hoozen, B E

    1999-01-01

    During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.

  11. Physiological effects of the amphetamines during exercise ...

    African Journals Online (AJOL)

    Oxygen consumption, heart rate, minute ventilation and blood lactate were measured on two champion cyclists at work rates from 45 to 362 W (2 000 - 16 000 ft-Ib / min) on a bicycle ergometer after administration of a placebo and after 10 mg of methamphetamine, without their knowledge of which was given. No differences ...

  12. physiological effects of the amphetamines during exercise

    African Journals Online (AJOL)

    Oxygen consumption, heart rate, minute ventilation and blood lactate were measured on two champion cyclisTs at work rates from 45 to 362 W (2 000 - 16 000 ft-Ib / min) on a bicycle ergometer after administration of a placebo and after 10 mg of methamphetamine, withoUT their know- ledge of which was given.

  13. Amphetamine, mazindol, and fencamfamin in narcolepsy.

    Science.gov (United States)

    Shindler, J; Schachter, M; Brincat, S; Parkes, J D

    1985-01-01

    Twenty patients with the narcoleptic syndrome were treated separately with dexamphetamine sulphate tablets 10 and 30 mg, Dexedrine Spansules 10 mg, mazindol 4 mg, and fencamfamin hydrochloride 60 mg daily. Each drug was given for four weeks and the effects compared. In these dosages the reported frequency of attacks of narcolepsy was roughly halved with each treatment, dexamphetamine 30 mg daily being only slightly more potent than 10 mg. The subjective effects of Dexedrine tablets and Spansules could not be distinguished by most patients. Effects on mood, alertness, and sympathomimetic side effects were largely inseparable with all these drugs, but a decrease in appetite was not reported by patients with narcolepsy. PMID:2859077

  14. Efficacy and safety of mixed amphetamine salts extended release (Adderall XR) in the management of attention-deficit/hyperactivity disorder in adolescent patients: a 4-week, randomized, double-blind, placebo-controlled, parallel-group study.

    Science.gov (United States)

    Spencer, Thomas J; Wilens, Timothy E; Biederman, Joseph; Weisler, Richard H; Read, Stephanie C; Pratt, Raymond

    2006-02-01

    The ability to recognize and diagnose attention-deficit/hyperactivity disorder (ADHD) has increased in recent years. The persistence of ADHD symptoms puts adolescents with ADHD at risk for long-term adverse psychosocial outcomes. The primary goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) in the management of adolescents with ADHD. This was a 4-week, randomized, multicenter, double-blind, placebo-controlled, parallel-group, forced-dose-titration study. Adolescents aged 13 to 17 years with ADHD were randomized to 1 of 4 active treatments (MAS XR 10, 20, 30 or 40 mg/d) or to placebo. All doses were given in the morning. This study used a forced-dose-titration design in which patients randomized to the 10-mg/d group received 1 dose of 10 mg/d for 4 weeks. Patients randomized to the 20-mg/d group received 1 dose of 10 mg/d for the first week and 1 dose of 20 mg/d for the remaining weeks; patients randomized to the 30-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, and 1 dose of 30 mg/d for the remaining 2 weeks; and patients randomized to the 40-mg/d group received 1 dose of 10 mg/d for the first week, 1 dose of 20 mg/d for the second week, 1 dose of 30 mg/d for the third week, and 1 dose of 40 mg/d for the fourth week. The primary efficacy measure was change from baseline to end point in the ADHD Rating Scale-IV (ADHD-RS-IV) score. The secondary efficacy measure was the score on the Clinical Global Impressions-Improvement (CGI-I) scale for ADHD. ADHD-RS-IV total scores were analyzed post hoc in patients with low baseline ADHD-RS-IV severity (ie, patients with baseline ADHD-RS-IV total scores less than the median) and high baseline ADHD-RS-IV severity (ie, patients with baseline ADHD-RS-IV total scores greater than the median). Safety was assessed by recording adverse events, vital signs, and body weight at all study visits and 30 days after drug

  15. Desenvolvimento e validação de um método cromatográfico em fase gasosa para análise da 3,4-metilenodioximetanfetamina (ecstasy e outros derivados anfetamínicos em comprimidos Development and validation of a gas chromatography method for determination of ecstasy and amphetamines derivatives in tablets

    Directory of Open Access Journals (Sweden)

    Marcelo Carvalho Lasmar

    2007-06-01

    Full Text Available O uso abusivo das anfetaminas e seus derivados vêm aumentando dramaticamente nos últimos anos em diversas regiões do mundo, notando-se especial utilização do Ecstasy. A análise de amostras da droga apreendidas nas ruas evidenciou, além da presença de MDMA (3,4-metilenodioximetanfetamina, componente principal da droga, outras feniletilaminas, como a MDA (3,4-metilenodioxanfetamina e MDEA (metilenodioximetiletilanfetamina este último também conhecido como a droga Eve, ainda pouco difundida no Brasil. O objetivo do presente trabalho foi desenvolver e validar um método analítico confiável, prático e acessível aos laboratórios de toxicologia, de médio e pequeno porte, no Brasil e em países em desenvolvimento, para identificação separada do MDMA, MDA e MDEA. A cromatografia em fase gasosa utilizando-se coluna capilar e detector de ionização de chama foi a técnica escolhida. O método analítico apresentou para os três analitos de interesse, faixa ampla de linearidade (1,0 a 500,0 µg/mL; limites de quantificação de 1,0 µg/mL e coeficientes de variação intra e interensaio inferiores a 9,5%. Os limites de detecção estabelecidos foram 0,7 µg/mL, 0,8 µg/mL e 0,6 µg/mL, respectivamente para o MDMA, MDA e MDEA. O método foi seletivo na presença de epinefrina, cocaína, anfetamina, ácido acetilsalisílico, metanfetamina, ácido dietilbarbitúrico, p-aminobenzoil dietilbarbitúrico, paracetamol e cafeína.The abusive use of the amphetamine derivative ecsyasy in the world come increasing in the last years. Many tablets samples kept on the streets shown the presence not only of the MDMA- 3,4-methylenedioxymethamphetamine, the main drug component but also of the MDA - 3,4- methylenedioxyamphetamine and MDEA - 3,4-methylenedioxymethylethylamphetamine. The present study sought to develop and validate an analytical method for determination of MDMA, MDA and MDEA in tablets to be accessible for the most small or medium

  16. Range of application of J-123-amphetamine in neurology

    International Nuclear Information System (INIS)

    Podreka, I.; Hoell, K.; Dal-Bianco, P.; Mamoli, B.; Roszucky, A.; Angelberger, P.

    1984-01-01

    Using a dual head rotating scintillation camera (Siemens Rota ZLC 37) IMP-SPECT studies of the brain were carried out in 100 patients with different neurologic disorders (apoplexy, epilepsy) and in 5 normal subjects. In 90 cases CT of the skull was equally ordered. In patients with epilepsy EEGs were recorded at the time of SPECT. The results obtained with these procedures were compared. In patients with compromised cerebral blood flow IMP studies consistently showed lesions compatible with the clinical signs and symptoms, while the CT scan was often normal in the presence of transient cerebrovascular episodes. In about 70% of patients with epilepsy a lesion was demonstrated by both EEG and IMP so that epileptogenic foci were successfully visualized. In 2 instances acoustic stimulation was associated with a regionally increased IMP uptake in the temporal lobe area bilaterally. Using the microsphere model described by Kuhl and associates, an attempt was made to quantify cerebral blood flow. For this purpose a scatter correction was introduced before reconstructing the images (filtered back projection). In this manner clinically relevant flow levels were computed in 10 cases. (Author)

  17. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

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

    2006-01-01

    -induced cell surface DAT redistribution may result in long-lasting changes in DA homeostasis. The molecular mechanism by which AMPH induces trafficking is not clear. Because AMPH is a substrate, we do not know whether extracellular AMPH stimulates trafficking through its interaction with DAT and subsequent...... alteration in DAT function, thereby triggering intracellular signaling or whether AMPH must be transported and then act intracellularly. In agreement with our previous studies, extracellular AMPH caused cytosolic redistribution of the wild-type human DAT (WT-hDAT). However, AMPH did not induce cytosolic...... redistribution in an uptake-impaired hDAT (Y335A-hDAT) that still binds AMPH. The divalent cation zinc (Zn(2+)) inhibits WT-hDAT activity, but it restores Y335A-hDAT uptake. Coadministration of Zn(2+) and AMPH consistently reduced WT-hDAT trafficking but stimulated cytosolic redistribution of Y335A...

  18. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

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

    2012-01-01

    and ROA spectra. As predicted the experimental ROA spectra were found to depend on the chirality. Two street samples, provided by the London Police, were also measured and compared to the calculated ROA spectra. The street samples were found to contain different enantiomers of the protonated am- phetamine...

  19. Efficacy and safety of mixed amphetamine salts extended release (adderall XR) in the management of oppositional defiant disorder with or without comorbid attention-deficit/hyperactivity disorder in school-aged children and adolescents: A 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study.

    Science.gov (United States)

    Spencer, Thomas J; Abikoff, Howard B; Connor, Daniel F; Biederman, Joseph; Pliszka, Steven R; Boellner, Samuel; Read, Stephanie C; Pratt, Raymond

    2006-03-01

    Oppositional defiant disorder (ODD)is associated with a high degree of impairment in social skills, family interaction, and academic functioning. Comorbid ODD is reportedly present in 40% to 70% of children and adolescents with attention-deficit/hyperactivity disorder (ADHD). The goal of this study was to assess the efficacy and safety of mixed amphetamine salts extended release (MAS XR) for the treatment of ODD in children and adolescents aged 6 to 17 years. This was a 4-week, multicenter, randomized, double-blind, parallel-group, placebo-controlled, forced-dose-escalation study. Patients were randomized to receive active treatment with MAS XR 10, 20, 30, or 40 mg/d or placebo. The primary efficacy end point was the ODD subscale of the Swanson, Nolan, and Pelham-IV (SNAP-IV) parent rating. Primary safety measures included adverse events recorded at each visit and for 30 days after study drug discontinuation, and changes in vital signs, 12-lead electrocardiographic (ECG) findings, laboratory tests and physical examinations, and body weight. A post hoc efficacy reanalysis was completed based on the results for the per-protocol population. For this analysis, patients were divided into high and low baseline severity categories according to the dichotomized baseline ODD parent or teacher score or dichotomized baseline ADHD parent or teacher score (high defined as scores at the median or greater and low defined as scores less than the median). A total of 308 children and adolescents (age range, 6-17 years; 213 males, 95 females) were randomized to receive active treatment with MAS XR 10 mg/d (n = 60) 20 mg/d (n = 58), 30 mg/d (n = 69), or 40 mg/d (n = 61) or placebo (n = 60). Of the 308 study patients, 244 (79.2%) had comorbid ADHD. A significant change from baseline in the ODD symptoms measured with the SNAP-IV parent rating subscale was found for the MAS XR 30-mg/d (-0.52; P < 0.001) and 40-mg/d (-0.56; P = 0.002) groups in the per-protocol analysis and for the MAS XR

  20. Placebo-controlled evaluation of amphetamine mixture-dextroamphetamine salts and amphetamine salts (Adderall): efficacy rate and side effects.

    Science.gov (United States)

    Ahmann, P A; Theye, F W; Berg, R; Linquist, A J; Van Erem, A J; Campbell, L R

    2001-01-01

    The primary objective of this study was to determine the efficacy rate of Adderall in children newly diagnosed with attention-deficit/hyperactivity disorder (ADHD). A secondary objective was to address the severity of side effects associated with Adderall treatment in children with ADHD using the Barkley Side Effects Questionnaire (BSEQ). Randomized, double-blind, placebo-controlled crossover trial. A large rural tertiary care clinic. Participants were prospectively recruited from children 5 to 18 years of age referred for academic and/or attention problems; 154 children who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for ADHD were enrolled. Interventions. Two doses of Adderall (0.15 mg/kg/dose and 0.3 mg/kg/dose) were compared with placebo in separate 2-week trials. Participants received each dosage regimen twice daily for 7 consecutive days. Efficacy rates were determined by comparing Adderall with placebo during the low-dose crossover sequence and also during the high-dose crossover sequence. The criteria that defined a positive response to Adderall relative to placebo (with each patient serving as their own control) included an indication of response by at least 1 of 2 parent measures of children's behavior or at least 2 of 5 teacher measures of children's behavior. The Adderall efficacy rate was determined based on parent criteria alone, teacher criteria alone, and by a more stringent definition of response that required concurrence between parent and teacher criteria. The Adderall response rate in this study ranged from 59% when requiring concurrence between parent and teacher observers, to 82% when based on parent criteria alone. Overall, 137 of 154 participants (89%) showed a positive response by either the parent or teacher response criteria. Parents completed a modified version of the BSEQ during each week of the trial. Appetite, stomachaches, and insomnia were rated as worse by parents while children were receiving either dose of Adderall; headaches were rated as worse when children were receiving the higher dose of Adderall. Parents rated certain side effects, including staring/daydreaming, sadness, euphoria, and anxious/irritable, as worse during placebo regimens. We found that Adderall is highly efficacious in our population of youth diagnosed with ADHD. In addition, Adderall is well-tolerated with a side effect profile similar to that reported for other psychostimulants.

  1. Spect with 123 I-amphetamine as a diagnostic aid for neurogical diseases

    International Nuclear Information System (INIS)

    Fill, H.; Vogl, G.; Zechmann, W.; Gerstenbrand, F.; Riccabona, G.

    1984-01-01

    In the past years computer tomography and Doppler sonography have reduced the importance of radionuclide studies in the diagnosis of neurologic disorders. However, a new family of tracers has recently been developed for tomographic imaging of cerebral blood flow. To establish the value of this new method 44 patients with neurologic disorders have sofar been investigated. As the number of patients was relatively small for drawing definitive conclusions on the usefulness of the procedure in a great variety of neurologic conditions, patients were referred for imaging without disclosure of the diagnosis. The data obtained were subsequently compared to the clinical and other findings. Sofar patients with TIA, PRIND, brain infarction, ICH, SAB, epilepsy, migraine, decerebrate syndrome and CO intoxication were examined. The studies, which were originally confined to patients with cerebral infarction, consistently showed a close correlation with CT findings, with hypoperfused areas invariably exceeding the size of the structural lesions. In clinically manifest TIA and PRIND with normal CT compromised flow in the affected areas was noted throughout. Similarly, a good agreement was seen in 'migraine accompagnee'. In patients after SAB areas of angiospastic hypoperfusion were recognizable. Functional deficits associated with CO intoxication and decerebrate syndrome were much more expensive than the morphological lesions seen on CT. Results obtained todate suggest that SPECT is useful in complementing existing studies for the diagnosis of neurologic disorders. (Author)

  2. Augmented reinforcer value and accelerated habit formation after repeated amphetamine treatment.

    NARCIS (Netherlands)

    Nordquist, R.E.; Voorn, P.; de Mooij-van Malsen, J.G.; Joosten, R.N.J.M.A.; Pennartz, C.M.A.; Vanderschuren, L.J.M.J.

    2007-01-01

    Various processes might explain the progression from casual to compulsive drug use underlying the development of drug addiction. Two of these, accelerated stimulus-response (S-R) habit learning and augmented assignment of motivational value to reinforcers, could be mediated via neuroadaptations

  3. Amphetamine Exerts Dose-Dependent Changes in Prefrontal Cortex Attractor Dynamics during Working Memory

    OpenAIRE

    Lapish, C.C.; Balaguer-Ballester, Emili; Seamans, J.K.; Phillips, A.G.; Durstewitz, D.

    2015-01-01

    Modulation of neural activity by monoamine neurotransmitters is thought to play an essential role in shaping computational neurodynamics in the neocortex, especially in prefrontal regions. Computational theories propose that monoamines may exert bidirectional (concentration-dependent) effects on cognition by altering prefrontal cortical attractor dynamics according to an inverted U-shaped function. To date, this hypothesis has not been addressed directly, in part because of the absence of app...

  4. Cocaine- and amphetamine-regulated transcript (CART) peptide specific binding in pheochromocytoma cells PC12

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Šloncová, Eva; Elbert, Tomáš; Slaninová, Jiřina; Železná, Blanka

    2007-01-01

    Roč. 559, 2/3 (2007), s. 109-114 ISSN 0014-2999 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514; CEZ:AV0Z50200510 Keywords : radioligand binding * CART * PC12 cells * food intake Subject RIV: CE - Biochemistry Impact factor: 2.376, year: 2007

  5. Strukturně-aktivní studie fragmentů peptidu "cocaine - and amphetamine regulated transcript"

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Blokešová, Darja; Železná, Blanka; Maletínská, Lenka

    2008-01-01

    Roč. 102, č. 5 (2008), s. 384-384 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků. Konference Sigma-Aldrich /8./. 10.06.2008-13.06.2008, Devět skal - Žďárské vrchy] R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptide * fragments * binding * PC12 cells Subject RIV: CE - Biochemistry

  6. Peptid CART (cocaine- and amphetamine- regulated transcript) v signalizaci buněk PC12

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 108, č. 5 (2014), s. 543 ISSN 0009-2770. [Mezioborové setkání mladých biologů, biochemiků a chemiků /14./. 13.05.2014-16.05.2014, Milovy] R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : peptide CART * PC12 * c-Jun * SAPK/JNK Subject RIV: CE - Biochemistry

  7. Structure-activity relationship of CART (cocaine- and amphetamine-regulated transcript) peptide fragments

    Czech Academy of Sciences Publication Activity Database

    Maixnerová, Jana; Hlaváček, Jan; Blokešová, Darja; Kowalczyk, W.; Elbert, Tomáš; Šanda, Miloslav; Blechová, Miroslava; Železná, Blanka; Slaninová, Jiřina; Maletínská, Lenka

    2007-01-01

    Roč. 28, č. 10 (2007), s. 1945-1953 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptide * fragments * binding * PC12 cells Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.368, year: 2007

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

    DEFF Research Database (Denmark)

    Lind, N. M.; Arnfred, S. M.; Hemmingsen, R. P.

    2004-01-01

    Prepulse inhibition (PPI) of the startle reflex is an operational measure of sensorimotor gating. The dopamine receptor agonist-mediated disruption of PPI in rats is widely used as a model of the sensorimotor gating deficiencies demonstrated in schizophrenia patients. As a possible tool for valid...

  9. Pathophysiologic study of chronic infarcts with I-123 isopropyl iodo-amphetamine (IMP)

    DEFF Research Database (Denmark)

    Raynaud, C; Rancurel, G; Samson, Y

    1987-01-01

    Seventeen chronic cerebral infarcts were investigated by a highly sensitive, dedicated brain single photon emission computerized tomography system using 123I-isopropyl iodoamphetamine (IMP) and 133Xe. IMP uptake was measured 10 minutes, 2 hours, and 5 hours after injection, and regional cerebral...... blood flow was measured with 133Xe. In 4 cases a positron emission tomography system was used to measure the rCBF and the regional metabolic rate of oxygen with C15O2 and 15O2. The results obtained allowed us to identify 2 abnormal zones. One, the "central area," was characterized by a severe decrease...... in IMP uptake and rCBF averaging 34% and 46% respectively and by a hypodense image on the x-ray computerized tomography scan. The second, the periinfarct or "peripheral area" was characterized by a moderate decrease in IMP uptake and regional cerebral blood flow averaging 13 and 19% respectively...

  10. NTP-CERHR EXPERT PANEL REPORT ON THE REPRODUCTIVE AND DEVELOPMENTAL TOXICITY OF AMPHETAMINE AND METHAMPHETAMINE.

    Science.gov (United States)

    A manuscript describes the results of an expert panel meeting of the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR). The purpose CERHR is to provide timely, unbiased, scientifically sound evaluations of human and experimental evidence for adverse effects ...

  11. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms

    NARCIS (Netherlands)

    Achterberg, E.J.M.; Trezza, V.; Siviy, S.M.; Schrama, L.H.; Schoffelmeer, A.N.; Vanderschuren, L.J.M.J.

    2014-01-01

    Rationale Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems

  12. Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms

    NARCIS (Netherlands)

    Achterberg, E.J.M.; Trezza, V.; Siviy, S.M.; Schrama, L.; Schoffelmeer, A.N.M.; Vanderschuren, L.J.M.J.

    2014-01-01

    Rationale: Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems

  13. Amphetamine Challenge: A Marker of Brain Function that Mediates Risk for Drug and Alcohol Abuse

    Science.gov (United States)

    2008-05-01

    Zuckerman, M., Eysenck , S., & Eysenck , H. J. (1978). Sensation seeking in England and America: Cross-cultural, age, and sex comparisons. Journal of...what success I have. A. True B. False 208. Some of my most vivid memories are called up by scents and smells. A. True B. False 209. I am a... memories ;" for example, after I’ve been swimming, I may still feel as if I’m in the water. A. True B. False 232. Striving for excellence means more

  14. Functional brain imaging with I123-amphetamine. First experience in the Netherlands

    NARCIS (Netherlands)

    de Bruïne, J. F.; van Royen, E. A.; van Weeren, F.; vd Weel, F. A.; Reiffers, S.; Verbeeten, B. W.; Krens, H.; Hijdra, A.; Limburg, M.

    1986-01-01

    Single Photon Emission Computed Tomography (SPECT) has been used in the last five years as a method for cerebral bloodflow imaging, especially in cerebral infarction. In this study the first experiences in the Netherlands are presented. In 57.6% of our patients lesions, defined by SPECT were larger

  15. Dopamine D2/3 receptor availability and amphetamine-induced dopamine release in obesity

    NARCIS (Netherlands)

    van de Giessen, Elsmarieke; Celik, Funda; Schweitzer, Dave H.; van den Brink, Wim; Booij, Jan

    2014-01-01

    The neurotransmitter dopamine is important in the regulation of food intake. It is hypothesised that obese people experience less reward from food due to lower striatal dopamine release, which consequently leads to overeating. This study is the first to assess whether obese subjects have blunted

  16. Evaluation of individual subjects in the analog classroom setting: II. Effects of dose of amphetamine (Adderall).

    Science.gov (United States)

    Wigal, S B; Swanson, J M; Greenhill, L; Waslick, B; Cantwell, D; Clevenger, W; Davies, M; Lerner, M; Regino, R; Fineberg, E; Baren, M; Browne, R

    1998-01-01

    Multiple dependent variables were graphed for 29 subjects who participated in a double-blind evaluation of 4 doses of Adderall, plus positive (methylphenidate) and placebo control conditions. Five judges ranked the conditions for each subject, and analyses of individual subjects indicated that these rankings were concordant (reliable) across judges. Consensus rankings were assigned to each subject, and an analysis of these ranks showed that the conditions differed significantly. The choice of best conditions were judged to be across 3 doses of Adderall (10, 15, and 20 mg). This confirms the clinical impression of individual differences in optimal dose of stimulant medication. The methodological, graphical, and statistical methods presented in this article provide a systematic, reliable procedure for evaluating relative response of individuals to different doses of stimulant medication.

  17. Pathophysiologic study of chronic infarcts with I-123 isopropyl iodo-amphetamine (IMP)

    DEFF Research Database (Denmark)

    Raynaud, C; Rancurel, G; Samson, Y

    1987-01-01

    Seventeen chronic cerebral infarcts were investigated by a highly sensitive, dedicated brain single photon emission computerized tomography system using 123I-isopropyl iodoamphetamine (IMP) and 133Xe. IMP uptake was measured 10 minutes, 2 hours, and 5 hours after injection, and regional cerebral ...

  18. Amphetamine Action at the Cocaine- and Antidepressant-Sensitive Serotonin Transporter Is Modulated by αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Montgomery, Therese R; Hofmaier, Tina

    2015-01-01

    Serotonergic neurotransmission is terminated by reuptake of extracellular serotonin (5-HT) by the high-affinity serotonin transporter (SERT). Selective 5-HT reuptake inhibitors (SSRIs) such as fluoxetine or escitalopram inhibit SERT and are currently the principal treatment for depression...

  19. The Role of Hypothalamic Insulin and Dopamine in the Anorectic Effect of Cocaine and d-amphetamine

    Science.gov (United States)

    1992-08-21

    chest pains, respiratory paralysis, cardiac arrhythmias , syncope, and myoclonic jerking (Siegel, 1987). One strong behavioral effect of cocaine is...insulin binding to blood-brain-barrier in vivo and to brain microvessels in vitro in newborn rabbits. Diabetes, ~, 728-733 . Frolich, A., & Loewi, O

  20. Semiquantifying regional cerebral blood flow by dynamic CT scanning; Correlation with sup 123 I-amphetamine (IMP) SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Totaro; Kasahara, Eishi; Takahashi, Eriko; Kojima, Seiichi (Municipal of Higashimatsuyama Hospital, Saitama (Japan)); Ogawa, Haruhiko; Suzuki, Keiko; Miyamae, Tatsuya; Yamazaki, Setsuo

    1990-10-01

    The study was undertaken to evaluate the semi-quantitative significance of the absolute value obtained by calculating the regional cerebral blood flow index (rCBFI) from dynamic CT in comparison with SPECT. rCBFI was calculated from mean transit time (MTT) and blood capacity index (BCI) obtained by rapidly infusing 50 ml of Omnipurk into the elbow vein by the use of Hitachi's W-600. (rCBFI=BCI/MTT unit/sec (U/S)) measurment of the rCBF by SPECT was made according to the semi-quantitative method by Matsuda et al. by the use of SHIMADZU's improved type HEADTOME SET-050 with rapid infusion of {sup 123}I-IMP in 3.5 m Ci from the elbow vein. Patients in whom no abnormality was observed in the cardiopulmonary function were enrolled as subjects. The rCBFI in each intracranial site was calculated from dynamic CT in 10 normal adults (aged 35-60, averaging 46.7) as subjects and compared with the rCBF obtained from SPECT in the same cases and same site. Comparative investigation was made similarly between rCBFI and rCBF regarding 10 patients with tracranial diseases (age 29-65, averaging 51.2). The mean rCBFIs in the normal adults obtained from dynamic CT were 1.15+-0.18 U/S in the frontal lobar cortex, 1.28+-0.19 U/S in the temporal lobar cortex, 1.43+-0.1 U/S in the occipital lobar cortex, 1.27+-0.2 U/S in the basal ganglia region and 0.43+-0.1 U/S in the white matter. On the other hand, the mean rCBFs by SPECT were 47.36+-3.93 ml/100 g/min, 55.19+-2.22 ml/100 g/min, 61.92+-5.42 ml/100 g/min, 54.38+-3.51 ml/100 g/min and 38.68+-6.18 ml/100 g/min, respectively. Positive correlation was observed between rCBFIs and rCBFs of 10 normal adults and 10 patients with intracranial disease, totalling 20 cases (r=0.79, P<0.005). The rCBFI by dynamic CT has a correlation with the rCBF by SPECT, suggesting the possibility of its evaluation as an absolute value, though semi-quantitatively. (author).

  1. Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Pirnik, Z.; Kiss, A.; Železná, Blanka

    2008-01-01

    Roč. 9, č. 101 (2008), s. 1-10 ISSN 1471-2202 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50200510 Keywords : mice * food intake * CART peptide Subject RIV: CE - Biochemistry Impact factor: 2.850, year: 2008

  2. Feeding-related effects of cart (cocaine and amphetamine regulated transcript) peptides and cholecystokinin in mouse obese models

    Czech Academy of Sciences Publication Activity Database

    Maletínská, Lenka; Maixnerová, Jana; Toma, Resha Shamas; Haugvicová, Renata; Slaninová, Jiřina; Železná, Blanka

    2006-01-01

    Roč. 12, Supplement (2006), s. 178 ISSN 1075-2617. [European Peptide Symposium /29./. 03.09.2006-08.09.2006, Gdansk] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART peptides * food intake * mouse obesity * CCK Subject RIV: CC - Organic Chemistry

  3. Structure-activity relationship of cocaine- and amphetamine-regulated transcript (CART) by peptide analogs: Importance of disulfide bridges

    Czech Academy of Sciences Publication Activity Database

    Blechová, Miroslava; Nagelová, Veronika; Demianova, Zuzana; Železná, Blanka; Maletínská, Lenka

    2012-01-01

    Roč. 18, S1 (2012), S89-S90 ISSN 1075-2617. [European Peptide Symposium /32./. 02.09.2012-07.09.2012, Athens] Institutional research plan: CEZ:AV0Z40550506 Keywords : CART * neuropeptides * cell line PC12 * anorexigenic effect Subject RIV: CE - Biochemistry

  4. Behavioral and Cardiac Responses to Mild Stress in Young and Aged Rats : Effects of Amphetamine and Vasopressin

    NARCIS (Netherlands)

    Buwalda, B.; Koolhaas, J.M.; Bohus, B.

    1992-01-01

    Young (3-month-old) male Wistar rats showed a relative decrease in heart rate to a sudden silence superimposed on low intensity background noise. This bradycardia was accompanied by immobility behavior. In 26-month-old rats the magnitude of the heart rate response was reduced while immobility

  5. Corrigendum to "Destruction of amphetamine in aqueous solution using gamma irradiation" [Radiat. Phys. Chem. 139 (2017) 17-21

    Science.gov (United States)

    Alkhuraiji, Turki S.; Ajlouni, Abdul-Wali; Alotaibi, Noura A.

    2018-04-01

    The authors regret to have omitted to add a co-author in the author list of this research article. They would like to add the following author who has contributed to the article: Noura A. Alotaibi, King Fahad Medical City, Riyadh, Saudi Arabia.

  6. Social play behavior, ultrasonic vocalizations and their modulation by morphine and amphetamine in Wistar and Sprague-Dawley rats

    NARCIS (Netherlands)

    Manduca, A.; Campolongo, P.; Pamery, M.; Vanderschuren, L.J.M.J.; prof.dr. Cuomo, V.; Trezza, V.

    2014-01-01

    Rationale Social play behavior is the most characteristic social behavior in young mammals. It is highly rewarding and crucial for proper neurobehavioral development. Despite the importance of genetic factors in normal and pathological social behaviors, little information is available about strain

  7. 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

    ), methamphetamine (MA), methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA or ecstasy). An intra-day precision of 3-6% RSD and an inter-day precision of 3-17% RSD were observed. Trueness was between 96 % and 106% for the target compounds. The limit of detection ranged from 0.07 to 0.14 ng...

  8. Effects of amphetamine and methylphenidate on attentional performance and impulsivity in the mouse 5-Choice Serial Reaction Time Task

    DEFF Research Database (Denmark)

    Caballero Puntiverio, Maitane; Fitzpatrick, Ciarán Martin; Woldbye, David Paul Drucker

    2017-01-01

    -attentive (HA) subgroup. Premature responses were increased by 1 mg/kg AMPH and 0.5 mg/kg MPH for all animals, and by 1 mg/kg AMPH for the LI subgroup. Conclusions: The use of variable stimulus duration, along with the division into high- and LA, and high-and LI subgroups, may improve the sensitivity of the 5...

  9. Caffeine promotes hyperthermia and serotonergic loss following co-administration of the substituted amphetamines, MDMA ("Ecstasy") and MDA ("Love").

    Science.gov (United States)

    McNamara, Ruth; Kerans, Aoife; O'Neill, Barry; Harkin, Andrew

    2006-01-01

    The present study determined the effect of caffeine co-administration on the core body temperature response and long-term serotonin (5-HT) loss induced by methylenedioxymethamphetamine (MDMA; "Ecstasy") and its metabolite methylenedioxyamphetamine (MDA; "Love") to rats. In group-housed animals, caffeine (10 mg/kg) enhanced the acute toxicity of MDMA (15 mg/kg) and MDA (7.5 mg/kg), resulting in an exaggerated hyperthermic response (+2 degrees C for 5 h following MDMA and +1.5 degrees C for 3 h following MDA) when compared to MDMA (+1 degree C for 3 h) and MDA (+1 degree C for 1 h) alone. Co-administration of caffeine with MDMA or MDA was also associated with increased lethality. To reduce the risk of lethality, doses of MDMA and MDA were reduced in further experiments and the animals were housed individually. To examine the effects of repeated administration, animals received MDMA (10 mg/kg) or MDA (5 mg/kg) with or without caffeine (10 mg/kg) twice daily for 4 consecutive days. MDMA and MDA alone induced hypothermia (fall of 1 to 2 degrees C) over the 4 treatment days. Co-administration of caffeine with MDMA or MDA resulted in hyperthermia (increase of up to 2.5 degrees C) following acute administration compared to animals treated with caffeine or MDMA/MDA alone. This hyperthermic response to caffeine and MDMA was not observed with repeated administration, unlike caffeine + MDA, where hyperthermia was obtained over the 4 day treatment period. In addition, 4 weeks after the last treatment, co-administration of caffeine with MDA (but not MDMA) induced a reduction in 5-HT and 5-hydroxyindole acetic acid (5-HIAA) concentrations in frontal cortex (to 61% and 58% of control, respectively), hippocampus (48% and 60%), striatum (79% and 64%) and amygdala (63% and 37%). However, when caffeine (10 mg/kg) and MDMA (2.5 mg/kg) were co-administered four times daily for 2 days to group-housed animals, both hyperthermia and hippocampal 5-HT loss were observed (reduced to 68% of control). Neither MDMA nor MDA alone induced a significant reduction in regional 5-HT or 5-HIAA concentrations following repeated administration. In conclusion, caffeine promotes the acute and long-term toxicity associated with MDMA and MDA. This is a serious drug interaction, which could have important acute and long-term health consequences for recreational drug users.

  10. Long-lasting nicotinic modulation of GABAergic synaptic transmission in the rat nucleus accumbens associated with behavioural sensitization to amphetamine

    NARCIS (Netherlands)

    de Rover, M.; Mansvelder, H.D.; Lodder, J.C.; Wardeh, G.; Schoffelmeer, A.N.M.; Brussaard, A.B.

    2004-01-01

    A robust increase in dopaminergic transmission in the nucleus accumbens (NAc) shell has been reported to be consistently associated with the long-term expression of behavioural sensitization to drugs of abuse. However, little is known about how this affects the neuronal network of the NAc. We made

  11. Fluoxetine

    Science.gov (United States)

    ... in U.S., Zagam); amphetamines such as amphetamine (in Adderall), dextroamphetamine (Dexedrine, Dextrostat, in Adderall), and methamphetamine (Desoxyn); anticoagulants ('blood thinners') such as ...

  12. SOLID-PHASE EXTRACTION FOLLOWED BY DISPERSIVE LIQUID ...

    African Journals Online (AJOL)

    Preferred Customer

    amphetamine (MDPA), drug testing for amphetamines is routinely done in forensic toxicology. Amphetamines are ... assess amphetamines compounds in human urine samples using gas chromatography (GC) [3], high-performance ... liquid extraction (LLE) that uses microliter volumes of the extraction solvent. For DLLME,.

  13. Effects of (Des-Tyr1)-γ-endorphin and α-endorphin as compared to haloperidol and amphetamine on nucleus accumbens self-stimulation

    NARCIS (Netherlands)

    Ree, J.M. van; Otte, A.P.

    The β-endorphin fragment (Des-Tyr1)-γ-endorphin (DTγE, β-LPH 62–77) attenuated self-stimulation behaviour associated with electrical stimulation of the nucleus accumbens area of rats. This effect was observed after subcutaneous (s.c.) injection of 2.5 and 25 μg of the neuropeptide and appeared to be

  14. Association of cocaine- and amphetamine-related transcript, leptin and leptin receptor gene polymorphisms with anthropometric obesity phenotype indicators in South African learners.

    Science.gov (United States)

    Yako, Y Y; Fanampe, B L; Hassan, M S; Erasmus, R T; van der Merwe, L; van Rensburg, S J; Matsha, T E

    2011-01-01

    Obesity has increased rapidly in South African children and adolescents. Genes involved in appetite regulation have been extensively studied worldwide, but their role in the obesity phenotype in South African Black and mixed-ancestry school adolescents is unknown. Seven common polymorphisms in LEP, GHRL, CART and LEPR were analysed for genotype and haplotype association with anthropometric obesity phenotype indicators in South African Black and mixed-ancestry adolescent school learners. The CART c.517A→G polymorphism was significantly associated with obesity susceptibility. The LEPR Lys(109)Arg G allele was associated with an average reduction of 2.36 kg/m(2) in body mass index (BMI), 5.66 cm in waist circumference (WC) and 1.61 cm in mid-upper-arm circumference (MUAC). This was confirmed by haplotype analysis. Additionally, a haplotype of the LEP polymorphisms significantly increased BMI, MUAC and hip circumference, while LEPR haplotypes were associated with differences in MUAC. Our findings suggest that c.517A→G and Lys(109)Arg contribute to the variation in anthropometric obesity phenotype indicators observed among Black African and mixed-ancestry South African learners. Furthermore, haplotypes of LEP, LEPR and GHRL polymorphisms were associated with varying measurements of weight, BMI and WC. Further studies are required to confirm our results in a larger and homogeneous study population group. Copyright © 2011 S. Karger AG, Basel.

  15. 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

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... 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...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  16. Estimation of BDNF gene polymorphism and predisposition to dependence development for selected psychoactive compounds: genetic aspects of addiction with the selected drugs, amphetamine, tetrahydrocannabinol and opiates.

    Science.gov (United States)

    Biskupska, J; Borowiak, K S; Karlin-Grazewicz, K; Janus, T; Waloszczyk, P; Potocka-Banas, B; Machoy-Mokrzynska, A; Ossowski, A; Ciechanowicz, A

    2013-03-01

    The etiology of drug addiction, a central nervous system (CNS) disease, is not fully known. This complex problem is believed to be connected with concurrently affecting genetic, psychological and environmental factors. The development of addiction is connected with CNS reinforcement system and dopaminergic neurotransmission. Molecular processes are postulated to be of universal character and allow to presume a similar mechanism of dependence for both ethanol and other substances. Therefore, elements of dopaminergic transmission become excellent candidates for the examination of genetic influence on the development of addiction. A relationship between alcoholic disease and the presence of TaqIA1 and DRD2 alleles permits to initiate another investigation of gene-coding DRD2 dopamine receptor. The latest results indicate the importance of brain-derived neurotrophic factor (BDNF) in the regulation of dopaminergic route. The purpose of this research was to reveal the relationship between the Val66Met BDNF gene polymorphism and dependence of psychoactive agent. The examinations were performed with the Local Research Ethics Committee approval and patient's consent. The study group consisted of 100 patients (88 men and 12 women) aged 18-52 years, qualified for research program according to the International Classification of Diseases, Tenth Revision (ICD-10) requirements, medical examination and detailed questionnaire.

  17. 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

    It has been argued that agonist ligands for dopamine D(2/3) receptors recognize a privileged subset of the receptors in living striatum, those which are functionally coupled to intracellular G-proteins. In support of this claim, the D(2/3) agonist [(3)H]-N-propylnorapomorphine ([(3)H]NPA) proved...... from endogenous dopamine, as seen in the lesioned side of 6-OHDA induced hemi-parkinsonism....

  18. Cocaine and amphetamine-regulated transcript (CART) concentration in maternal and cord blood in type 1 diabetic and non diabetic pregnancies at term

    LENUS (Irish Health Repository)

    Hehir, MP

    2011-02-01

    Institute of Obstetricians & Gynaecologists, RCPI Four Provinces Meeting, Junior Obstetrics & Gynaecology Society Annual Scientific Meeting, Royal Academy of Medicine in Ireland Dublin Maternity Hospitals Reports Meeting Nov 2010

  19. Anorexigenic effect of cholecystokinin is lost but that of CART (cocaine and amphetamine regulated transcript) peptide is preserved in monosodium glutamate obese mice

    Czech Academy of Sciences Publication Activity Database

    Železná, Blanka; Maixnerová, Jana; Matyšková, Resha; Haugvicová, Renata; Blokešová, Darja; Maletínská, Lenka

    2009-01-01

    Roč. 58, č. 5 (2009), s. 717-723 ISSN 0862-8408 R&D Projects: GA ČR GA303/05/0614 Grant - others:GA ČR(CZ) GA305/06/0427 Program:GA Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z5020903 Keywords : monosodium glutamate (MSG) obesity * neuropeptide Y (NPY) * cholecystokinin Subject RIV: CC - Organic Chemistry Impact factor: 1.430, year: 2009

  20. Radioenzymatic paper-chromatographic assay for dopamine and norepinephrine in cerebroventricular cisternal perfusate of cat following administration of cocaine or d-amphetamine

    International Nuclear Information System (INIS)

    Chiueh, C.C.; Kopin, I.J.

    1978-01-01

    A sensitive radioenzymatic paper chromatographic method was used to measure the endogenous dopamine and norepinephrine content of cerebroventricular cisternal perfusate from cats to provide direct evidence for the catecholamine releasing action of cocaine from brain in vivo. Although relatively less potent than d-emphetamine, cocaine was shown to release endogenous catechloramines, mainly dopamine from the brain. This similarity may be the neurochemical basis for their similar behavioral effects. (U.K.)

  1. Determination of amphetamine-type stimulants (ATSs) and synthetic cathinones in urine using solid phase micro-extraction fibre tips and gas chromatography-mass spectrometry

    OpenAIRE

    Alsenedi, Khalid A.; Morrison, Calum

    2018-01-01

    In recent years, an increasing number of stimulant drugs and new psychoactive substances (NPSs) have caused concern in scientific communities and therefore innovative methods to extract compounds from complex biological samples are required. This work is aimed at developing and validating a clean, convenient and straightforward extraction procedure with microliter amounts of organic solvent using Solid Phase Micro-Extraction tips (SPME tips) and analysis using Gas Chromatography-Mass Spectrom...

  2. Perinatal Effects of Combined Use of Heroin, Methadone, and Amphetamine during Pregnancy and Quantitative Measurement of Metabolites in Hair

    Directory of Open Access Journals (Sweden)

    Pen-Hua Su

    2012-04-01

    Conclusion: The current study suggested the possibility of polydrug exposure, which was previously unknown in pregnant women in Taiwan. Measurement of neonatal hair samples could provide a basis for clinical evaluation and potential corresponding treatment.

  3. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    Energy Technology Data Exchange (ETDEWEB)

    Milhazes, Nuno [CEQOFFUP, Faculdade de Farmacia, Universidade do Porto (Portugal); Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal); Instituto Superior de Ciencias da Saude-Norte, Gandra, Paredes (Portugal); Martins, Pedro [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Uriarte, Eugenio [Departamento de Quimica Organica, Facultade de Farmacia, Universidad de Santiago de Compostela (Spain); Garrido, Jorge [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Engenharia Quimica, ISEP, Instituto Politecnico do Porto (Portugal); Calheiros, Rita [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Marques, M. Paula M. [Unidade I and D ' Quimica-Fisica Molecular' (Portugal); Departamento de Bioquimica, Faculdade de Ciencias e Tecnologia, Universidade de Coimbra (Portugal); Borges, Fernanda [Departamento de Quimica Organica, Faculdade de Farmacia, Universidade do Porto (Portugal) and Unidade I and D ' Quimica-Fisica Molecular' (Portugal)]. E-mail: fborges@ff.up.pt

    2007-07-23

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-{beta}-methyl-{beta}-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared.

  4. Electrochemical and spectroscopic characterisation of amphetamine-like drugs: Application to the screening of 3,4-methylenedioxymethamphetamine (MDMA) and its synthetic precursors

    International Nuclear Information System (INIS)

    Milhazes, Nuno; Martins, Pedro; Uriarte, Eugenio; Garrido, Jorge; Calheiros, Rita; Marques, M. Paula M.; Borges, Fernanda

    2007-01-01

    A complete physicochemical characterisation of MDMA and its synthetic precursors MDA, 3,4-methylenedioxybenzaldehyde (piperonal) and 3,4-methylenedioxy-β-methyl-β-nitrostyrene was carried out through voltammetric assays and Raman spectroscopy combined with theoretical (DFT) calculations. The former provided important analytical redox data, concluding that the oxidative mechanism of the N-demethylation of MDMA involves the removal of an electron from the amino-nitrogen atom, leading to the formation of a primary amine and an aldehyde. The vibrational spectroscopic experiments enable to afford a rapid and reliable detection of this type of compounds, since they yield characteristic spectral patterns that lead to an unequivocal identification. Moreover, the rational synthesis of the drug of abuse 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy') from one of its most relevant precursors 3,4-methylene-dioxyamphetamine (MDA), is reported. In addition, several approaches for the N-methylation of MDA, a limiting synthetic step, were attempted and the overall yields compared

  5. Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys

    DEFF Research Database (Denmark)

    Madsen, Morten V; Peacock, Linda; Werge, Thomas

    2006-01-01

    Several clinical studies have shown that alterations in the cannabinoid system in the brain may be associated with schizophrenia. Although evidence points towards an antipsychotic potential for cannabinoid antagonists, experimental studies have shown inconsistent behavioural effects of cannabinoid...

  6. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition

    International Nuclear Information System (INIS)

    Herdon, H.; Strupish, J.; Nahorski, S.R.

    1985-01-01

    Direct comparisons between radiolabelled and endogenous dopamine (DA) release from superfused rat brain slices have been made. Striatal slices were prelabelled with [ 3 H]dopamine ([ 3 H]DA), then superfused at 0.5 ml/min and the released catecholamines analyzed by HPLC with electrochemical detection and radioactivity present in superfusate fractions also counted. The studies indicate that labelled and endogenous amine release do not always occur in parallel, and that major causes of discrepancy between them may include the presence of a large newly-synthesized component in endogenous release and the uneven distribution of labelled amine within endogenous releasable pools. The results also suggest that the prelabelling process itself may alter the pools contributing to subsequent endogenous release. (Auth.)

  7. Consumption of anorexigenic amphetamine-like drugs (diethylpropion, fenproporex and mazindol) and of d,1-fenfluramine in Brazil during the years of 1988 and 1989.

    Science.gov (United States)

    Nappo, S A

    1996-01-01

    Brazilian consumption of psychostimulant anorexigenic drugs--diethylpropion, fenproporex, and mazindol--and of 3,1-fenfluramine was studied, and results are presented in terms of DDDs/1000 inhabitants/day. As of 1988, consumption of these drugs in Brazil was equal to 4.59 DDDs/1000 inhabitants/day; in the following year it had risen by 43.8%. However, if only the population that can afford to buy medicines is considered, actual consumption figures are at least three times higher. Such numbers point to a very high rate of anorexigenic consumption in Brazil, in contrast with other countries where use of these drugs is smaller. It was also found that 68.6% of total consumption in 1988--and 39.4% in 1989--corresponded to prescription formulas prepared by specialized pharmacies, while the remainder was consumed in the form of ready-made medicines produced by pharmaceutical industries. The most used drugs were mazindol in 1988, and fenproporex in 1989; d,1-fenfluramine was the least used of these substances in both years. These reasons are discussed for this increased consumption in Brazil and the absence of an adequate controlling attitude on the part of public health authorities.

  8. Orexinergic innervation of urocortin1 and cocaine and amphetamine regulated transcript neurons in the midbrain centrally projecting Edinger-Westphal nucleus.

    NARCIS (Netherlands)

    Emmerzaal, T.L.; Doelen, R.H.A. van der; Roubos, E.W.; Kozicz, L.T.

    2013-01-01

    Orexin is a neuropeptide that has been implicated in several processes, such as induction of appetite, arousal and alertness and sleep/wake regulation. Multiple lines of evidence also suggest that orexin is involved in the stress response. When orexin is administered intracerebroventricular it

  9. Genetic targeting of the amphetamine and methylphenidate-sensitive dopamine transporter: On the path to an animal model of attention-deficit hyperactivity disorder

    Science.gov (United States)

    Mergy, Marc A.; Gowrishankar, Raajaram; Davis, Gwynne L.; Jessen, Tammy N.; Wright, Jane; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

    2014-01-01

    Alterations in dopamine (DA) signaling underlie the most widely held theories of molecular and circuit level perturbations that lead to risk for attention-deficit hyperactivity disorder (ADHD). The DA transporter (DAT), a presynaptic reuptake protein whose activity provides critical support for DA signaling by limiting DA action at pre- and postsynaptic receptors, has been consistently associated with ADHD through pharmacological, behavioral, brain imaging and genetic studies. Currently, the animal models of ADHD exhibit significant limitations, stemming in large part from their lack of construct validity. To remedy this situation, we have pursued the creation of a mouse model derived from a functional nonsynonymous variant in the DAT gene (SLC6A3) of ADHD probands. We trace our path from the identification of these variants to in vitro biochemical and physiological studies to the production of the DAT Val559 mouse model. We discuss our initial findings with these animals and their promise in the context of existing rodent models of ADHD. PMID:24332984

  10. The impact of the withdrawal of Adderall XR (long-acting mixed amphetamine salts) from the Canadian market on paediatric patients and their families.

    Science.gov (United States)

    Cheng, Anita; Tithecott, Gary A; Edwards, Wendy E; Johnston, Ian G

    2007-05-01

    Adderall XR (Shire BioChem Inc, Canada), a medication used to treat attention deficit hyperactivity disorder, was withdrawn from the Canadian market in February 2005 due to concerns of possible cardiotoxicity and cerebral vascular events among a small number of individuals who had taken the medication. The primary objective of the present study was to investigate the degree to which the physician's relationship with the families of the patients to whom the medication was prescribed was affected by the withdrawal of Adderall XR from the Canadian market. The study sought to explore the perceptions of caregivers of patients who took Adderall XR to the drug recall. As a secondary objective, the study also assessed the differences in perception of caregivers toward physicians compared with their perception of other agencies involved with the recall. Questionnaires were sent to the caregivers of 123 patients who had been taking the drug at the time of the withdrawal. Of the 53 (43%) completed questionnaires, 89% of respondents indicated that they were concerned when informed of the withdrawal, while 58% indicated that they were frightened. Despite the concerns, only a modest degree of anger was expressed. Thirty per cent of respondents reported anger directed at Health Canada, 24% reported anger directed at the manufacturer, while no caregiver reported anger directed at their physician. Only three families (5.7%) indicated a decrease in confidence in the physician following the event. Fifty-eight per cent indicated a willingness to resume taking Adderall XR, if it was deemed safe by Health Canada. These results offer insight into patient and family perspectives following an unexpected medication recall. While caregivers were generally concerned and often frightened by this event, the present data do not suggest that the parent-physician relationship was greatly affected.

  11. CART (cocaine- and amphetamine-regulated transcript) peptide specific binding sites in PC12 cells have characteristics of CART peptide receptors

    Czech Academy of Sciences Publication Activity Database

    Nagelová, Veronika; Pirnik, Z.; Železná, Blanka; Maletínská, Lenka

    2014-01-01

    Roč. 1547, Feb 14 (2014), s. 16-24 ISSN 0006-8993 R&D Projects: GA ČR GAP303/10/1368 Institutional support: RVO:61388963 Keywords : CART peptide * PC12 cell * differentiation * binding * signaling * c-Jun Subject RIV: CE - Biochemistry Impact factor: 2.843, year: 2014

  12. Effect of Exposure to Lithium-Paired or Amphetamine-Paired Saccharin Solution on Open Arm Avoidance in an Elevated Plus Maze

    Science.gov (United States)

    Rana, Shadna A.; Parker, Linda A.

    2006-01-01

    Recent evidence suggests that drug-induced conditioned taste avoidance may be mediated by conditioned fear (e.g., Parker, 2003). The experiments reported here evaluated the effect of exposure to a drug-paired flavor on open arm exploration in an elevated plus maze (EPM), a measure of fear. When rats were tested on a familiar (trial 2) EPM, but not…

  13. Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine

    NARCIS (Netherlands)

    Hennissen, L.; Bakker-Huvenaars, M.J.; Banaschewski, T.; Carucci, S.; Coghill, D.; Danckaerts, M.; Dittmann, R.W.; Hollis, C.; Kovshoff, H.; McCarthy, S.; Nagy, P.; Sonuga-Barke, E.; Wong, I.C.; Zuddas, A.; Rosenthal, E.; Buitelaar, J.K.

    2017-01-01

    BACKGROUND: Many children and adolescents with attention deficit/hyperactivity disorder (ADHD) are treated with stimulant and non-stimulant medication. ADHD medication may be associated with cardiovascular effects. It is important to identify whether mean group effects translate into clinically

  14. Effect of anorexinergic peptides, cholecystokinin (CCK) and cocaine and amphetamine regulated transcript (CART) peptide, on the activity of neurons in hypothalamic structures of C57Bl/6 mice involved in the food intake regulation

    Czech Academy of Sciences Publication Activity Database

    Pirnik, Z.; Maixnerová, Jana; Matyšková, Resha; Koutová, Darja; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2010-01-01

    Roč. 31, č. 1 (2010), s. 139-144 ISSN 0196-9781 R&D Projects: GA ČR GA303/05/0614 Institutional research plan: CEZ:AV0Z40550506 Keywords : cholecystokinin * CART * hypocretin * Fos peptide Subject RIV: CE - Biochemistry Impact factor: 2.654, year: 2010

  15. Effect of traditional medicine brahmi vati and bacoside A-rich fraction of Bacopa monnieri on acute pentylenetetrzole-induced seizures, amphetamine-induced model of schizophrenia, and scopolamine-induced memory loss in laboratory animals.

    Science.gov (United States)

    Mishra, Amrita; Mishra, Arun K; Jha, Shivesh

    2018-03-01

    Brahmi vati (BV) is an Ayurvedic polyherbal formulation used since ancient times and has been prescribed in seizures associated with schizophrenia and related memory loss by Ayurvedic practitioners in India. The aim of the study was to investigate these claims by evaluation of anticonvulsant, antischizophreniac, and memory-enhancing activities. Antioxidant condition of brain was determined by malondialdehyde (MDA) and reduced glutathione (GSH) levels estimations. Acetylcholinesterase (AChE) was quantitatively estimated in the brain tissue. Brahmi vati was prepared in-house by strictly following the traditional Ayurvedic formula. Bacoside A rich fraction (BA) of Bacopa monnieri was prepared by extraction and fractionation. It was than standardized by High Performance Liquid Chromatography (HPLC) and given in the dose of 32.5mg/kg body weight to the different groups of animals for 7days. On the seventh day, activities were performed adopting standard procedures. Brahmi vati showed significant anticonvulsant, memory-enhancing and antischizophrenia activities, when compared with the control groups and BA. It cause significantly higher brain glutathione levels. Acetylcholinesterase activity was found to be significantly low in BV-treated group. The finding of the present study suggests that BV may be used to treat seizures associated with schizophrenia and related memory loss. Copyright © 2018 Elsevier Inc. All rights reserved.

  16. 77 FR 47114 - Manufacturer of Controlled Substances; Notice of Application; AMRI Rensselaer, Inc.

    Science.gov (United States)

    2012-08-07

    ... Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II Lisdexamfetamine (1205) II... (Marihuana), the company plans to bulk manufacture cannabidiol as a synthetic intermediate, which will be...

  17. Intracellular Methamphetamine Prevents the Dopamine-induced Enhancement of Neuronal Firing*

    Science.gov (United States)

    Saha, Kaustuv; Sambo, Danielle; Richardson, Ben D.; Lin, Landon M.; Butler, Brittany; Villarroel, Laura; Khoshbouei, Habibeh

    2014-01-01

    The dysregulation of the dopaminergic system is implicated in multiple neurological and neuropsychiatric disorders such as Parkinson disease and drug addiction. The primary target of psychostimulants such as amphetamine and methamphetamine is the dopamine transporter (DAT), the major regulator of extracellular dopamine levels in the brain. However, the behavioral and neurophysiological correlates of methamphetamine and amphetamine administration are unique from one another, thereby suggesting these two compounds impact dopaminergic neurotransmission differentially. We further examined the unique mechanisms by which amphetamine and methamphetamine regulate DAT function and dopamine neurotransmission; in the present study we examined the impact of extracellular and intracellular amphetamine and methamphetamine on the spontaneous firing of cultured midbrain dopaminergic neurons and isolated DAT-mediated current. In dopaminergic neurons the spontaneous firing rate was enhanced by extracellular application of amphetamine > dopamine > methamphetamine and was DAT-dependent. Amphetamine > methamphetamine similarly enhanced DAT-mediated inward current, which was sensitive to isosmotic substitution of Na+ or Cl− ion. Although isosmotic substitution of extracellular Na+ ions blocked amphetamine and methamphetamine-induced DAT-mediated inward current similarly, the removal of extracellular Cl− ions preferentially blocked amphetamine-induced inward current. The intracellular application of methamphetamine, but not amphetamine, prevented the dopamine-induced increase in the spontaneous firing of dopaminergic neurons and the corresponding DAT-mediated inward current. The results reveal a new mechanism for methamphetamine-induced dysregulation of dopaminergic neurons. PMID:24962577

  18. A Comparison of Psychotomimetic Drug Effects on Rat Brain Norepinephrine Metabolism

    Science.gov (United States)

    1973-02-19

    Thor. 189: 42-50,1974. V The effects of LSD, psilocybin, mescaline, amphetamine and cold water swimming stress on the metabolism of ’H-norepinephrine...to ef- C.ARR, L. A. AND Mooc , K E.: Norepincphrinv: 50 STOLK ET AL. Vol. 189’ Release from brain by d-amphetamine in vivo. SMITH, C. B.: Effects of d

  19. Psychoactive substances in seriously injured drivers in Denmark

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Steentoft, Anni; Bernhoft, Inger Marie

    2013-01-01

    at levels above LOQ, whereas amphetamines (5.4%) (amphetamine [5.2%] and methamphet-amine [1.5%]), tetrahydrocannabinol (3.7%), and cocaine (3.3%), including the metabolite benzoylecgo-nine, were the most frequently detected illegal drugs. A driver could be positive for more than one substance; therefore...

  20. Review: Methamphetamine use by pregnant women: Impact on the ...

    African Journals Online (AJOL)

    According to the United Nations Office on Drugs and Crime (UNODC)'s 2011 World Drug Report, amphetamine-type stimulants (ATS) are the second most widely used illicit drug group. This drug group comprises methamphetamine, amphetamine and ecstasy. Methamphetamine is the most widely manufactured drug in this ...

  1. Some remarks on the effects of drugs, lack of sleep and loud noise on human performance.

    NARCIS (Netherlands)

    Sanders, A.F. & A.A. Bunt.

    1971-01-01

    Some literature is reviewed on the effect of some drugs, (amphetamine, hypnotics, alcohol), loud noise and sleep loss in test of time estimation, decision making, long term performance and short term memory. Results are most clear with respect to amphetamine, hypnotics and lack of sleep, in that

  2. Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality

    Directory of Open Access Journals (Sweden)

    Maryam Akhgari

    2017-06-01

    Full Text Available Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

  3. Discrimination Between Drug Abuse and Medical Therapy: Case report of a tranylcypromine overdose-related fatality.

    Science.gov (United States)

    Akhgari, Maryam; Jokar, Farzaneh; Etemadi-Aleagha, Afshar; Ghasemi, Ali

    2017-05-01

    Tranylcypromine is an effective antidepressant from the class of monoamine oxidase inhibitors and is structurally related to amphetamine. However, reports differ regarding the potential metabolism of tranylcypromine to amphetamine and methamphetamine within the human body. We report a 25-year-old woman with severe depression who died due to a fatal tranylcypromine overdose in 2016. She had been prescribed tranylcypromine one day previously and had no history of previous suicide attempts or substance abuse. The body was transferred to a forensic medicine department in Tehran, Iran for the autopsy. A urine sample was positive for tranylcypromine, amphetamine and methamphetamine using gas chromatography/mass spectrometry after derivatisation with heptafluorobutyric acid. As amphetamines were present in the urine sample, it was assumed that the tranylcypromine had been converted to amphetamines metabolically. As such, it is possible that the legitimate use of certain prescription drugs may complicate the interpretation of test results for illegal drugs.

  4. Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, P.B.

    1987-03-09

    Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

  5. Differential regulation of the phosphorylation of Trimethyl-lysine27 histone H3 at serine 28 in distinct populations of striatal projection neurons

    DEFF Research Database (Denmark)

    Bonito-Oliva, Alessandra; Södersten, Erik; Spigolon, Giada

    2016-01-01

    Phosphorylation of histone H3 (H3) on serine 28 (S28) at genomic regions marked by trimethylation of lysine 27 (H3K27me3) often correlates with increased expression of genes normally repressed by Polycomb group proteins (PcG). We show that amphetamine, an addictive psychostimulant, and haloperidol...... of histone H3, decreases the effect of amphetamine, but not that of haloperidol. Chromatin immunoprecipitation analysis shows that amphetamine and haloperidol increase the phosphorylation of H3K27me3S28 at the promoter regions of Atf3, Npas4 and Lipg, three genes repressed by PcG. These results identify H3K...

  6. Cardiomyopathy due to ingestion of Adderall.

    Science.gov (United States)

    Marks, Donald H

    2008-01-01

    A patient is described who developed cardiomyopathy after receiving a therapeutic course of dextroamphetamine/amphetamine. The patient's cardiac function deteriorated to the point of heart failure, necessitating a heart transplantation. Cardiomyopathy associated with amphetamine use is a serious and potentially lethal condition. With early diagnosis, identification of the cause, and treatment, cardiomyopathy may be reversible. The dangers of therapeutic use of amphetamines are discussed, as well as problems and assumptions associated with U.S. Food and Drug Administration monitoring and removal from the market of harmful substances.

  7. 75 FR 47503 - Schedules of Controlled Substances; Placement of 2,5-Dimethoxy-4-(n)-propylthiophenethylamine and...

    Science.gov (United States)

    2010-08-06

    ... scientific data used to evaluate the abuse potential of drugs or other substances. In addition, potency...-mentioned animal studies, it has been shown that BZP is about 20 times less potent than amphetamine in...

  8. Bibliography [On Drugs].

    Science.gov (United States)

    National Association of Student Personnel Administrators, Detroit, MI.

    A bibliography of materials on drugs is presented. The book and paper back entries are annotated. Selected technical references are listed under these major findings: (1) dependency, (2) barbiturates, (3) amphetamines, and (4) general pharmacology. (PS)

  9. Disease: H01730 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available emand of heart. Cardiovascular disease ... Old age Tobacco smoking High blood pressure High levels of LDL High cholesterol and fat Diab...etes Obesity Chronic kidney disease Alcohol Cocaine Amphetamines ... Cardiac troponin

  10. Sex differences in methamphetamine pharmacokinetics in adult rats and its transfer to pups through the placental membrane and breast milk

    Czech Academy of Sciences Publication Activity Database

    Rambousek, Lukáš; Kačer, P.; Syslová, K.; Bumba, J.; Bubeníková-Valešová, V.; Šlamberová, R.

    2014-01-01

    Roč. 139, JUN (2014), s. 138-144 ISSN 0376-8716 Institutional support: RVO:67985823 Keywords : methamphetamine * amphetamine * pharmacokinetics * sex differences * breast feeding milk * mass spectrometry Subject RIV: FH - Neurology Impact factor: 3.423, year: 2014

  11. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    . To this end, we investigated the effects of xanomeline on the behavior induced by D-amphetamine and (-)-apomorphine in drug-naive Cebus apella monkeys. Antipsychotic compounds antagonize amphetamine-induced motor unrest and stereotypies in this species. Xanomeline inhibited D-amphetamine-induced motor unrest......, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when...... xanomeline was tested in EPS-sensitized Cebus apella monkeys, EPS were not observed at the dose range of xanomeline used in the D-amphetamine-apomorphine combination study (0.5-3 mg/kg). However, when xanomeline was tested at 4 mg/kg, moderate dystonia was seen in two out of three monkeys. It is concluded...

  12. Methamphetamine (Meth)

    Science.gov (United States)

    ... and severe mental problems, including paranoia, hallucinations, and delusions. Meth users often notice a feeling like insects ... What to Know Dealing With Addiction Bath Salts Cocaine Amphetamines I Think I May Have a Drinking/ ...

  13. 76 FR 30970 - Manufacturer of Controlled Substances; Notice of Registration

    Science.gov (United States)

    2011-05-27

    ... controlled substances: Drug Schedule Marihuana (7360) I Tetrahydrocannabinols (7370) I Amphetamine (1100) II... distribution to its customers. In reference to drug code 7360 (Marihuana), the company plans to bulk...

  14. Central nervous system stimulants and drugs that suppress appetite

    DEFF Research Database (Denmark)

    Aagaard, Lise

    2014-01-01

    of the January 2012 to June 2013 publications on central nervous system stimulants and drugs that suppress appetite covers amphetamines (including metamfetamine, paramethoxyamfetamine and paramethoxymetamfetamine), fenfluramine and benfluorex, atomoxetine, methylphenidate, modafinil and armodafinil...

  15. Fast and Highly Selective LC-MS/MS Screening for THC and 16 Other Abused Drugs and Metabolites in Human Hair to Monitor Patients for Drug Abuse

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background:To facilitate the monitoring of drug abuse by patients, a method was developed and validated for the analysis of amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine, benzoylecgonine, morphine,

  16. Malignant hyperthermia

    Science.gov (United States)

    ... with general anesthesia. Avoid stimulant drugs such as cocaine, amphetamine (speed), and ecstasy. These drugs may cause problems similar to MH in people who are prone to this condition. Genetic counseling is recommended for anyone with a family ...

  17. Application of Sweat Patch Screening for 16 Drugs and Metabolites Using a Fast and Highly Selective LC-MS/MS Method

    NARCIS (Netherlands)

    Koster, Remco A.; Alffenaar, Jan-Willem C.; Greijdanus, Ben; VanDerNagel, Joanneke E. L.; Uges, Donald R. A.

    Background: To facilitate the monitoring of drug abuse by patients, a method was developed and validated for fast and highly selective screening for amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, methylenedioxyamphetamine, methylenedioxyethylamphetamine, methylphenidate, cocaine,

  18. Rekreacyjne używanie leków dostępnych w odręcznej sprzedaży: odurzanie i doping mózgu

    Directory of Open Access Journals (Sweden)

    Aleksandra Piątek

    2015-03-01

    Pseudoephedrine, an amphetamine-like stimulant, produces mood improvement or even euphoria, hallucinations and psychosis. However, the real health threat is associated with the use of substances produced from pseudoephedrine: ephedrone and methamphetamine.

  19. Drugs: What You Should Know (For Teens)

    Science.gov (United States)

    ... Commonly abused drugs include: alcohol amphetamines bath salts cocaine cough and cold medicines (DXM) crack depressants GHB ... need. Several kinds of treatment are available for drug addiction . The two main types are behavioral (helping a ...

  20. Effect of autonomic blocking agents and structurally related substances on the “salt arousal of drinking”

    NARCIS (Netherlands)

    Wied, D. de

    The effect of autonomic blocking agents and structurally related substances was studied in rats in which thirst was produced by the administration of a hypertonic sodium chloride solution. Scopolamine, methamphetamine, amphetamine, chlorpromazine, atropine, mecamylamine, hexamethonium, nethalide,

  1. Teens Mix Prescription Opioids with Other Substances

    Science.gov (United States)

    ... Infographics » Teens Mix Prescription Opioids with Other Substances Teens Mix Prescription Opioids with Other Substances Email Facebook ... amphetamines (10.6%, 10.3%, and 9.5%). Teens who mix prescription opioids with other drugs are ...

  2. Hearing Voices and Seeing Things

    Science.gov (United States)

    ... prescribed or recommended. Illegal drugs such as alcohol, marijuana, amphetamines, cocaine, and LSD are a frequent cause of hallucinations. Nonpsychotic psychiatric illnesses Children who hear voices telling them to do bad things often have behavior problems. Voices that refer ...

  3. Study Drugs

    Science.gov (United States)

    ... What Are Study Drugs? Doctors prescribe medicines like Adderall and Ritalin to treat conditions like attention deficit ... stimulants are used as study drugs: amphetamines like Adderall, Dexedrine, or Vyvanse methylphenidates like Ritalin or Concerta ...

  4. Probing dopamine transporter structure and function by Zn2+-site engineering

    DEFF Research Database (Denmark)

    Loland, Claus Juul; Norgaard-Nielsen, Kristine; Gether, Ulrik

    2003-01-01

    used antidepressants as well as widely abused drugs such as cocaine and amphetamines. In spite of their pharmacological importance, still little is known about their higher structural organization and the molecular mechanisms underlying the substrate translocation process. In this review...

  5. Takayasu arteritis in young male

    African Journals Online (AJOL)

    2012-09-23

    Sep 23, 2012 ... Primary aldosteronism. Cushing's syndrome. Pheochromocytoma. Hyperthyroidism and hypothyroidism. Hyperparathyroidism. Pregnancy-induced hypertension. Drugs and toxins: Examples-cocaine, amphetamines, alcohol. How to cite this article: Patil BS, Rajoor UG. Takayasu arteritis in young male.

  6. The development and applications of polyclonal and monoclonal antibodies for the detection of illicit drugs in saliva samples

    OpenAIRE

    Fanning, Lorna M.

    2002-01-01

    Anti-tetrahydrocannabinol (THC), anti-cocaine and anti-morphine polyclonal antibodies were produced. These antibodies were successfully applied to an ELISA format for the detection of THC, cocaine, and morphine in saliva samples. Monoclonal antibodies against amphetamine and its derivatives were produced using two different conjugates, amphetamine-bovine serum albumin and methamphetaminebovine serum albumin. Two successful clones were produced, and the antibodies were applied to an ELISA ...

  7. Enantiomeric profiling of chiral drugs in wastewater and receiving waters

    OpenAIRE

    Kasprzyk-Hordern, Barbara; Baker, D R

    2012-01-01

    The aim of this paper is to discuss the enantiomer-specific fate of chiral drugs during wastewater treatment and in receiving waters. Several chiral drugs were studied: amphetamine-like drugs of abuse (amphetamine, methamphetamine, MDMA, MDA), ephedrines (ephedrine and pseudoephedrine), antidepressant venlafaxine, and beta-blocker atenolol. A monitoring program was undertaken in 7 WWTPs (utilizing mainly activated sludge and trickling filters technologies) and at 6 sampling points in receivin...

  8. Semiautomated radioimmunoassay for mass screening of drugs of abuse

    International Nuclear Information System (INIS)

    Sulkowski, T.S.; Lathrop, G.D.; Merritt, J.H.; Landez, J.H.; Noe, E.R.

    1975-01-01

    A rapid, semiautomated radioimmunoassay system for detection of morphine, barbiturates, and amphetamines is described. The assays are applicable to large drug abuse screening programs. The heart of the system is the automatic pipetting station which can accomplish 600 pipetting operations per hour. The method uses 15 to 30 μl for the amphetamine and combined morphine/barbiturate assays. A number of other drugs were tested for interference with the assays and the results are discussed

  9. Possible mechanisms involved in the vasorelaxant effect produced by clobenzorex in aortic segments of rats

    OpenAIRE

    Lozano-Cuenca, J.; González-Hernández, A.; López-Canales, O.A.; Villagrana-Zesati, J.R.; Rodríguez-Choreão, J.D.; Morín-Zaragoza, R.; Castillo-Henkel, E.F.; López-Canales, J.S.

    2017-01-01

    Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10?9?10?5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-...

  10. Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

    OpenAIRE

    Rezin, Gislaine T.; Scaini, Giselli; Gonçalves, Cinara L.; Ferreira, Gabriela K.; Cardoso, Mariane R.; Ferreira, Andréa G.K.; Cunha, Maira J.; Schmitz, Felipe; Varela, Roger B.; Quevedo, João; Wyse, Angela T.S.; Streck, Emilio L.

    2013-01-01

    Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of youn...

  11. Imported Fenproporex-based Diet Pills from Brazil: A Report of Two Cases

    OpenAIRE

    Cohen, Pieter A.

    2008-01-01

    Banned amphetamine-based anorectics are illicitly imported into the United States (US), but little is known regarding the harm these diet pills pose to US residents. A 26-year-old woman using imported diet pills presented with a two-year history of intermittent chest pains, palpitations, headaches and insomnia. Urine toxicology screen detected amphetamines and benzodiazepines. Fenproporex and chlordiazepoxide were detected in her pills. Her symptoms resolved after she stopped using diet pills...

  12. Acute administration of fenproporex increased acetylcholinesterase activity in brain of young rats

    OpenAIRE

    TEODORAK, BRENA P.; FERREIRA, GABRIELA K.; SCAINI, GISELLI; WESSLER, LETÍCIA B.; HEYLMANN, ALEXANDRA S.; DEROZA, PEDRO; VALVASSORI, SAMIRA S.; ZUGNO, ALEXANDRA I.; QUEVEDO, JOÃO; STRECK, EMILIO L.

    2015-01-01

    Fenproporex is the second most commonly amphetamine-based anorectic consumed worldwide; this drug is rapidly converted into amphetamine, in vivo, and acts by increasing dopamine levels in the synaptic cleft. Considering that fenproporex effects on the central nervous system are still poorly known and that acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine, the present study investigated the effects of acute...

  13. Adderall Induced Acute Liver Injury: A Rare Case and Review of the Literature

    OpenAIRE

    Vanga, Rohini R.; Bal, Bikram; Olden, Kevin W.

    2013-01-01

    Adderall (dextroamphetamine/amphetamine) is a widely prescribed medicine for the treatment of attention-deficit/hyperactivity disorder (ADHD) and is considered safe with due precautions. Use of prescribed Adderall without intention to overdose as a cause of acute liver injury is extremely rare, and to our knowledge no cases have been reported in the English literature. Amphetamine is an ingredient of recreational drugs such as Ecstacy and is known to cause hepatotoxicity. We describe here the...

  14. A gas chromatography-mass spectrometry method for the quantitation of clobenzorex.

    Science.gov (United States)

    Cody, J T; Valtier, S

    1999-01-01

    Drugs metabolized to amphetamine or methamphetamine are potentially significant concerns in the interpretation of amphetamine-positive urine drug-testing results. One of these compounds, clobenzorex, is an anorectic drug that is available in many countries. Clobenzorex (2-chlorobenzylamphetamine) is metabolized to amphetamine by the body and excreted in the urine. Following administration, the parent compound was detectable for a shorter time than the metabolite amphetamine, which could be detected for days. Because of the potential complication posed to the interpretation of amphetamin-positive drug tests following administration of this drug, the viability of a current amphetamine procedure using liquid-liquid extraction and conversion to the heptafluorobutyryl derivative followed by gas chromatography-mass spectrometry (GC-MS) analysis was evaluated for identification and quantitation of clobenzorex. Qualitative identification of the drug was relatively straightforward. Quantitative analysis proved to be a far more challenging process. Several compounds were evaluated for use as the internal standard in this method, including methamphetamine-d11, fenfluramine, benzphetamine, and diphenylamine. Results using these compounds proved to be less than satisfactory because of poor reproducibility of the quantitative values. Because of its similar chromatographic properties to the parent drug, the compound 3-chlorobenzylamphetamine (3-Cl-clobenzorex) was evaluated in this study as the internal standard for the quantitation of clobenzorex. Precision studies showed 3-Cl-clobenzorex to produce accurate and reliable quantitative results (within-run relative standard deviations [RSDs] clobenzorex.

  15. [Fatal poisoning due to narcotic abuse in the analytic-toxicological practice of Forensic Medicine Department Silesian Medical Academy in Katowice in years 1996-202].

    Science.gov (United States)

    Soja, Artur; Celiński, Rafał; Kulikowska, Joanna; Albert, Małgorzata; Sybirska, Halina

    2003-01-01

    147 cases of fatal poisonings in people due to narcotic abuse examined in the Forensic Medicine Department Silesian School of Medicine, Katowice in the years 1996-2002 have been presented in the paper. In the group examined there were 126 males and 21 females at the age of 16-44. Opium narcotics were found in 139 out of 147 cases and amphetamine derivatives in 18. Opiates were indicated in 58 individuals and amphetamine only in 8. In 35 poisoned people opiates with barbituric acid derivatives were found. In 3 cases death resulted after taking opiates and amphetamine derivatives. 1 individual died after taking opiates and substances of the phenothiazine group. In the organic fluids of 18 people opiates and medicines being derivatives of 1,4-benzodiazepine and barbituric acid were found. Amphetamine and derivatives of 1,4-benzodiazepine were found in 6 individuals and opiates, barbiturates, benzodiazepines and amphetamine in 1 individual. Concentrations of all the substances indicated ranged widely and were as follows: microgram/ml for opiates; microgram/ml for amphetamine; microgram/ml for 1.4-benzodiazepine derivatives and microgram/ml for barbituric acid derivatives. Ethanol was found in 18 individuals and its concentration was @1000.

  16. Lisdexamfetamine: chemistry, pharmacodynamics, pharmacokinetics, and clinical efficacy, safety, and tolerability in the treatment of binge eating disorder.

    Science.gov (United States)

    Ward, Kristen; Citrome, Leslie

    2018-02-01

    The indications for lisdexamfetamine (LDX), a central nervous system stimulant, were recently expanded to include treatment of moderate to severe binge eating disorder (BED). Areas covered: This review aims to describe the chemistry and pharmacology of LDX, as well as the clinical trials investigating the efficacy and safety of this medication for the management of BED. Expert opinion: LDX is the first medication with United States Food and Drug Administration approval for the treatment of BED. It is an inactive prodrug of d-amphetamine that extends the half-life of d-amphetamine to allow for once daily dosing. D-amphetamine acts primarily to increase the concentrations of synaptic dopamine and norepinephrine. Metabolism of LDX to d-amphetamine occurs when peptidases in red blood cells cleave the covalent bond between d-amphetamine and l-lysine. D-amphetamine is then further metabolized by CYP2D6. Excretion is primarily through renal mechanisms. In clinical trials, LDX demonstrated statistical and clinical superiority over placebo in reducing binge eating days per week at doses of 50 and 70 mg daily. Commonly reported side effects of LDX include dry mouth, insomnia, weight loss, and headache, and its use should be avoided in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia or coronary artery disease. As with all CNS stimulants, risk of abuse needs to be assessed prior to prescribing.

  17. 10th International Conference on Philosophy, Psychiatry and Psychology, Sun City

    Directory of Open Access Journals (Sweden)

    Editorial Office

    2007-08-01

    Full Text Available In the last few years much data in the gulf region indicate that amphetamine psychosis has become more common and more prolonged. Aim. This study was done to: 1 assess clinical features related to amphetamine withdrawal, 2 assess if there are changes in these features in comparison to other previous studies or not, 3 study the relation between amphetamine and chronicity of psychotic symptoms, 4 find a reason for such suspected changes if present. Methods. A total of 150 male amphetamine dependent inpatients were selected according to ICD-10 research diagnostic criteria. Patients were subjected to the following procedures: 1 Oral informed consent. 2 Full psychiatric interview. 3 Urine test for common addictive substances on admission 4 Symptoms checklist which have been designed by the authors to assess Clinical features associated with amphetamine 5 Symptom Checklist–90–Revised (Derogates 1994. Results. Generally the present study shows that the psychotic symptoms were very common with Amphetamine dependent patients and the severity of all symptoms decreased significantly during the different phases of treatment. Delusions and hallucinations were very common during 2nd week (54% and 51% respectively and persisted for more than 8 weeks in 24% and 10% of patients respectively. Discussion. Some of the results are similar to previous studies as Dalmau et al. 1999 and Koyama et al. 1991 but still the duration of psychosis is much longer. Conclusion. There is increased risk of psychosis with use of amphetamine and a lot of reasons may play role as starting abuse at early age, sensitization process that may lead to chronic psychosis, and adulterating substances like ephedrine that may be dangerous and can lead to permanent damage of brain serotonin nerve endings.

  18. Pressor responses to ephedrine are not impaired in dopamine β-hydroxylase knockout mice

    Science.gov (United States)

    Liles, J T; Baber, S R; Deng, W; Porter, J R; Corll, C; Murthy, S N; Thomas, S A; Kadowitz, P J

    2006-01-01

    Background and Purpose: Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model. Experimental Approach: Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine β-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh +/- littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments. Key Results: In Dbh -/- mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh +/- mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/- and Dbh +/- mice. Conclusions and Implications: The present results in Dbh -/- mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh +/- and Dbh -/- mice are useful for the study of direct and indirect mechanisms. PMID:17099719

  19. Pressor responses to ephedrine are not impaired in dopamine beta-hydroxylase knockout mice.

    Science.gov (United States)

    Liles, J T; Baber, S R; Deng, W; Porter, J R; Corll, C; Murthy, S N; Thomas, S A; Kadowitz, P J

    2007-01-01

    Ephedrine and amphetamine can cause substantial increases in systemic arterial pressure. However, the role of endogenous noradrenaline release in mediating the pressor response to ephedrine is controversial. Studies using pharmacologic agents to decrease the synthesis, storage, and release of catecholamines have supported both a direct and an indirect mechanism of action for ephedrine. The purpose of the present study was to determine if endogenous noradrenaline release is required for cardiovascular responses to ephedrine and amphetamine using a genetic mouse model. Increases in systemic arterial pressure and heart rate in response to ephedrine and amphetamine were investigated and compared in dopamine beta-hydroxylase knockout (Dbh -/-) mice that cannot synthesize noradrenaline. Dbh +/- littermates have normal noradrenaline and adrenaline tissue levels, and served as controls in all experiments. In Dbh -/- mice the increases in systemic arterial pressure and heart rate in response to i.v. injections of ephedrine were not impaired whereas responses to amphetamine were markedly reduced, when compared with responses in Dbh +/- mice. The pressor response to tyramine was abolished whereas pressor responses to noradrenaline, phenylephrine, dopamine, and angiotensin II were similar in Dbh -/- and Dbh +/- mice. The present results in Dbh -/- mice provide support for the hypothesis that pressor responses to ephedrine are directly mediated whereas responses to amphetamine are dependent on the release of noradrenaline and suggest that Dbh +/- and Dbh -/- mice are useful for the study of direct and indirect mechanisms.

  20. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) in toxicological analysis. Studies on the detection of clobenzorex and its metabolites within a systematic toxicological analysis procedure by GC-MS and by immunoassay and studies on the detection of alpha- and beta-amanitin in urine by atmospheric pressure ionization electrospray LC-MS.

    Science.gov (United States)

    Maurer, H H; Kraemer, T; Ledvinka, O; Schmitt, C J; Weber, A A

    1997-02-07

    GC-MS is the method of choice for toxicological analysis of toxicants volatile in GC while non-volatile and/or thermally labile toxicants need LC-MS for their determination. Studies are presented on the toxicological detection of the amphetamine-like anorectic clobenzorex in urine by GC-MS after acid hydrolysis, extraction and acetylation and by fluorescence polarization immunoassay (FPIA, TDx (meth)amphetamine II). After ingestion of 60 mg of clobenzorex, the parent compound and/or its metabolites could be detected by GC-MS for up to 84 h or by FPIA for up to 60 h. Since clobenzorex shows no cross-reactivity with the used immunoassay, the N-dealkylated metabolite amphetamine is responsible for the positive TDx results. The intake of clobenzorex instead of amphetamine can be differentiated by GC-MS detection of hydroxyclobenzorex which is detectable for at least as long as amphetamine. In addition, the described GC-MS procedure allows the simultaneous detection of most of the toxicologically relevant drugs. Furthermore, studies are described on the atmospheric pressure ionization electrospray LC-MS detection of alpha- and beta-amanitin, toxic peptides of amanita mushrooms, in urine after solid-phase extraction on RP-18 columns. Using the single ion monitoring mode with the ions m/z 919 and 920 the amanitins could be detected down to 10 ng/ml of urine which allows us to diagnose intoxications with amanita mushrooms.

  1. Analysis of forensic samples of "Ecstasy" tablets seized in Novi Sad during the 2004 year

    Directory of Open Access Journals (Sweden)

    Zgonjanin Dragana M.

    2005-01-01

    Full Text Available The paper presents results of the analysis of illicit synthetic drugs in the form of tablets distributed under the name "Ecstasy", seized by the police in the broader area of Novi Sad 2004. A huge number of tablets has been analyzed (n=121, of various colours and with impressed symbols from the total amount of 93 seizures, which totally amounted to 1458 tablets. Regarding the number of seizures ecstasy (3,4-methylendioxy-N-meth-yl-amphetamine - MDMA is dominant among all, and according to the quantity of seized tablets it is amphetamine (AP, while other amphetamine-type drugs (methamphetamine MA 3,4-methylendioxiamphetamine - MDA, 3,4-methylendioxi-N-ethyl-amphetamine MDEA have been found in rather small quantities and very rarely. Tablets mostly contain caffeine as an additive. In the analytical procedure, the samples of tablets were subjected to liquid-liquid extraction and afterwards analyzed on the GCD (GC-EI Hewlett-Packard instrument. The method is fast reliable and reproducible for the analysis of amphetamine, methamphetamine MDA, MDMA, MDEA, as well as various additives in the samples of seized tablets.

  2. Ca(2+)/calmodulin-dependent protein kinase IIα (αCaMKII) controls the activity of the dopamine transporter: implications for Angelman syndrome.

    Science.gov (United States)

    Steinkellner, Thomas; Yang, Jae-Won; Montgomery, Therese R; Chen, Wei-Qiang; Winkler, Marie-Therese; Sucic, Sonja; Lubec, Gert; Freissmuth, Michael; Elgersma, Ype; Sitte, Harald H; Kudlacek, Oliver

    2012-08-24

    The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signaling. DAT is also the primary target of psychostimulant drugs such as cocaine and amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder and narcolepsy. The action of amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase αCaMKII attenuates amphetamine-triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP(+)) efflux. More importantly, αCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that αCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice, which lack αCaMKII or which express a permanently self-inhibited αCaMKII (αCaMKII(T305D)), exhibit significantly reduced amphetamine-triggered DAT-mediated MPP(+) efflux. Additionally, we investigated mice that mimic a neurogenetic disease known as Angelman syndrome. These mice possess reduced αCaMKII activity. Angelman syndrome mice demonstrated an impaired DAT efflux function, which was comparable with that of the αCaMKII mutant mice, indicating that DAT-mediated dopaminergic signaling is affected in Angelman syndrome.

  3. Stimulant-induced trichotillomania.

    Science.gov (United States)

    Hamalian, Gareen; Citrome, Leslie

    2010-01-01

    A prior report described the presentation of cocaine-induced trichotillomania, which resolved with the cessation of cocaine use. Here the authors describe the case of stimulant-induced trichotillomania that resolved with the discontinuation of stimulants and initiation of olanzapine. To the authors' knowledge this is the first reported adult case of stimulant-induced trichotillomania. The case is of a patient with a previous diagnosis of attention deficit hyperactivity disorder whose symptoms of trichotillomania coincide with abuse of amphetamine and with the resolution of symptoms in the absence of amphetamine use. Given the increase in exposure of prescription amphetamines among adults, further study into the association between stimulants and adverse events such as trichotillomania is needed.

  4. Drug-related death in Denmark in 2007

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Hansen, A. Carsten; Rollmann, Dorte

    2011-01-01

    : The number of drug-related deaths in 2007 was 226. Methadone deaths had increased since 1997 while heroin/morphine deaths decreased. In earlier studies, very few deaths from central stimulants like cocaine and amphetamines occurred (1-1.5%), but in 2007 6% of the deaths were caused by these drugs. Multiple...... drug use was common. Heroin/morphine, cocaine, amphetamine, cannabis, methadone, benzodiazepines and alcohol were included in the poly-drug use. CONCLUSION: This investigation shows stabilization in the number of fatal poisonings in drug addicts. Geographic differences were observed. Methadone...... was the most frequent cause of fatal poisoning and there was a continuous decrease in heroin/morphine deaths. Fatal deaths from cocaine and amphetamine have increased considerably. Multiple drug use was common....

  5. (-)PPAP: a new and selective ligand for sigma binding sites.

    Science.gov (United States)

    Glennon, R A; Battaglia, G; Smith, J D

    1990-11-01

    Most agents employed for the investigation of sigma (sigma) binding sites display relatively low affinity for these sites, bind both at sigma sites and at either phencyclidine (PCP) sites or dopamine receptors with similar affinity, and/or produce some dopaminergic activity in vivo. We describe a new agent, (-)PPAP or R(-)-N-(3-phenyl-n-propyl)-1-phenyl-2-aminopropane hydrochloride, that binds with high affinity and selectivity at sigma (IC50 = 24 nM) versus either PCP sites (IC50 greater than 75,000 nM) or D1 and D2 dopamine receptors (IC50 greater than 5,000 nM). The sigma affinity of this agent is comparable to that of the standard ligands (+)-3-PPP and DTG. Furthermore, although (-)PPAP is structurally related to amphetamine, it neither produces nor antagonizes amphetamine-like stimulus effect in rats trained to discriminate 1 mg/kg of S(+)amphetamine from saline.

  6. Imported fenproporex-based diet pills from Brazil: a report of two cases.

    Science.gov (United States)

    Cohen, Pieter A

    2009-03-01

    Banned amphetamine-based anorectics are illicitly imported into the United States (US), but little is known regarding the harm these diet pills pose to US residents. A 26-year-old woman using imported diet pills presented with a two-year history of intermittent chest pains, palpitations, headaches and insomnia. Urine toxicology screen detected amphetamines and benzodiazepines. Fenproporex and chlordiazepoxide were detected in her pills. Her symptoms resolved after she stopped using diet pills. A 38-year-old man using imported diet pills presented after his occupational urine screen was significantly positive for amphetamine. Fenproporex and fluoxetine were detected in his pills. These cases illustrate the potential harm from imported prescription diet pills that combine fenproporex with benzodiazepines, antidepressants, diuretics, laxatives and other substances. Increasing physicians' awareness of imported diet pill use may improve care of patients suffering from the pills' many adverse effects.

  7. Acute recreational drug toxicity: Comparison of self-reports and results of immunoassay and additional analytical methods in a multicenter European case series.

    Science.gov (United States)

    Liakoni, Evangelia; Yates, Christopher; Dines, Alison M; Dargan, Paul I; Heyerdahl, Fridtjof; Hovda, Knut Erik; Wood, David M; Eyer, Florian; Liechti, Matthias E

    2018-02-01

    The aim of the study was to compare self-reported and analytically confirmed substance use in cases of acute recreational drug toxicity.We performed a retrospective analysis of emergency department presentations of acute recreational drug toxicity over 2 years (October 2013 to September 2015) within the European Drug Emergencies Network Plus project.Among the 10,956 cases of acute recreational drug toxicity during the study period, 831 could be included. Between the self-reported substance use and the toxicological results, the highest agreement was found for heroin (86.1%) and cocaine (74.1%), whereas inhalants, poppers, and magic mushrooms were self-reported but not analytically detected. Cathinones and other new psychoactive substances (NPS) could be detected using additional analytical methods. Among cases with both immunoassay (IA) and confirmation with mass spectrometry (MS), the results were consistent for methadone (100%) and cocaine (95.5%) and less consistent for amphetamines (81.8%). In cases with a positive IA for amphetamines (n = 54), MS confirmed the presence of 3,4-methylenedioxymethamphetamine (MDMA), amphetamine, methamphetamine, and NPS in 37, 20, 10, and 6 cases, respectively, also revealing use of more than 1 substance in some cases. MS yielded positive results in 21 cases with a negative IA for amphetamines, including amphetamine, MDMA, methamphetamine, and NPS, in 14, 7, 2, and 2 cases, respectively.In conclusion, the highest agreement was found between self-reports and analytical findings for heroin and cocaine. The diagnosis of NPS use was mainly based on self-report. The IAs accurately identified methadone and cocaine, and MS had advantages for the detection of NPS and amphetamine derivatives.

  8. Simultaneous use of alcohol with methamphetamine but not ecstasy linked with aggression among young adult stimulant users.

    Science.gov (United States)

    Leslie, Ellen M; Smirnov, Andrew; Cherney, Adrian; Wells, Helene; Legosz, Margot; Kemp, Robert; Najman, Jake M

    2017-07-01

    Illicit stimulants are often combined with alcohol in nightlife entertainment districts, an environment where aggressive behaviour commonly occurs. While alcohol and methamphetamine use are each associated with aggressive behaviour, relatively little is known about the impact of the combined use of alcohol and amphetamine-type stimulants (i.e., ecstasy [MDMA] and methamphetamine) on aggression. Analysis of longitudinal data from a population-based sample of Australian young adult amphetamine-type stimulant users (n=248) to examine: (a) prevalence and timing of simultaneous alcohol and amphetamine-type stimulant use and (b) predictors of ecstasy- and methamphetamine-related aggression and hostility. Prediction models of ecstasy- and methamphetamine-related aggression and hostility were developed using multivariate logistic regression. Simultaneous alcohol consumption and amphetamine-type stimulant use was prevalent, with drinking generally occurring before consuming amphetamine-type stimulants and while 'high'. Methamphetamine-related aggression and hostility was significantly associated with recurrent risky simultaneous methamphetamine and alcohol use (Adjusted Odds Ratio [AOR] 2.74, 95% CI 1.09-6.89), a high frequency and increasing use methamphetamine trajectory (AOR 7.23, 95% CI 1.27-41.03), and high trait aggression (AOR 5.78, 95% CI 2.53-13.20). In contrast, only trait aggression (moderate: AOR 3.01, 95% CI 1.55-5.84; high: AOR 5.02, 95% CI 2.38-10.61) was associated with ecstasy-related aggression and hostility. These findings indicate a link between risky patterns of simultaneous alcohol and methamphetamine use and methamphetamine-related aggression and hostility, independent of separate use of alcohol, methamphetamine and cannabis, trait aggression, psychosis, and gender. The policy challenges of amphetamine-type stimulant and alcohol use require a targeted, multidisciplinary approach. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Antipsychotic drug-like effects of the selective M4 muscarinic acetylcholine receptor positive allosteric modulator VU0152100.

    Science.gov (United States)

    Byun, Nellie E; Grannan, Michael; Bubser, Michael; Barry, Robert L; Thompson, Analisa; Rosanelli, John; Gowrishankar, Raajaram; Kelm, Nathaniel D; Damon, Stephen; Bridges, Thomas M; Melancon, Bruce J; Tarr, James C; Brogan, John T; Avison, Malcolm J; Deutch, Ariel Y; Wess, Jürgen; Wood, Michael R; Lindsley, Craig W; Gore, John C; Conn, P Jeffrey; Jones, Carrie K

    2014-06-01

    Accumulating evidence suggests that selective M4 muscarinic acetylcholine receptor (mAChR) activators may offer a novel strategy for the treatment of psychosis. However, previous efforts to develop selective M4 activators were unsuccessful because of the lack of M4 mAChR subtype specificity and off-target muscarinic adverse effects. We recently developed VU0152100, a highly selective M4 positive allosteric modulator (PAM) that exerts central effects after systemic administration. We now report that VU0152100 dose-dependently reverses amphetamine-induced hyperlocomotion in rats and wild-type mice, but not in M4 KO mice. VU0152100 also blocks amphetamine-induced disruption of the acquisition of contextual fear conditioning and prepulse inhibition of the acoustic startle reflex. These effects were observed at doses that do not produce catalepsy or peripheral adverse effects associated with non-selective mAChR agonists. To further understand the effects of selective potentiation of M4 on region-specific brain activation, VU0152100 alone and in combination with amphetamine were evaluated using pharmacologic magnetic resonance imaging (phMRI). Key neural substrates of M4-mediated modulation of the amphetamine response included the nucleus accumbens (NAS), caudate-putamen (CP), hippocampus, and medial thalamus. Functional connectivity analysis of phMRI data, specifically assessing correlations in activation between regions, revealed several brain networks involved in the M4 modulation of amphetamine-induced brain activation, including the NAS and retrosplenial cortex with motor cortex, hippocampus, and medial thalamus. Using in vivo microdialysis, we found that VU0152100 reversed amphetamine-induced increases in extracellular dopamine levels in NAS and CP. The present data are consistent with an antipsychotic drug-like profile of activity for VU0152100. Taken together, these data support the development of selective M4 PAMs as a new approach to the treatment of psychosis

  10. Drug use in college students: a 13-year trend

    Directory of Open Access Journals (Sweden)

    Gabriela Arantes Wagner

    2012-06-01

    Full Text Available OBJECTIVE: To analyze drug use trends among college students in 1996, 2001 and 2009. METHODS: A cross-sectional epidemiological study with a multistage stratified cluster sample with 9,974 college students was conducted in the city of São Paulo, southeastern Brazil. An anonymous self-administered questionnaire was used to collect information on drug use assessed in lifetime, the preceding 12 months and the preceding 30 days. The Bonferroni correction was used for multiple comparisons of drug use rates between surveys. RESULTS: There were changes in the lifetime use of tobacco and some other drugs (hallucinogens [6.1% to 8.8%], amphetamines [4.6% to 8.7%], and tranquilizers [5.7% to 8.2%] from 1996 to 2009. Differences in the use of other drugs over the 12 months preceding the survey were also seen: reduced use of inhalants [9.0% to 4.8%] and increased use of amphetamines [2.4% to 4.8%]. There was a reduction in alcohol [72.9% to 62.1%], tobacco [21.3% to 17.2%] and marijuana [15.0% to 11.5%] use and an increase in amphetamine use [1.9% to 3.3%] in the preceeding 30 days. CONCLUSIONS: Over the 13-year study period, there was an increase in lifetime use of tobacco, hallucinogens, amphetamines, and tranquilizers. There was an increase in amphetamine use and a reduction in alcohol use during the preceding 12 months. There was an increase in amphetamine use during the preceding 30 days.

  11. Fatal poisoning among patients with drug addiction

    DEFF Research Database (Denmark)

    Simonsen, K. W.; Christoffersen, D. J.; Banner, J.

    2015-01-01

    in 2012 were included in the study. Results: A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71......%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent...

  12. Fatal poisoning among patients with drug addiction

    DEFF Research Database (Denmark)

    Simonsen, Kirsten Wiese; Christoffersen, Dorte J; Banner, Jytte

    2015-01-01

    in 2012 were included in the study. RESULTS: A total of 188 fatal intoxications were recorded. The median age increased from 37.5 in 2007 to 41.5 in 2012. The majority were men (77%). Methadone (59%) was the main intoxicant. The decrease in the frequency of heroin/morphine deaths since 1997 (71......%) continued, declining to 44% in 2002, 33% in 2007 and finally to 27% in 2012. Few deaths from central stimulants (amphetamine and cocaine) occurred. Multiple drug use was common and consisted mainly of opioids, cocaine, amphetamine, cannabis, benzodiazepines and alcohol. Heroin/morphine use was most frequent...

  13. Synthesis and serotonin transporter activity of 1,3-bis(aryl)-2-nitro-1-propenes as a new class of anticancer agents

    DEFF Research Database (Denmark)

    McNamara, Yvonne M.; Cloonan, Suzanne M.; Knox, Andrew J.S.

    2011-01-01

    Structural derivatives of 4-MTA, an illegal amphetamine analogue have been previously shown to have anticancer effects in vitro. In this study we report the synthesis of a series of novel 1,3-bis(aryl)-2-nitro-1-propene derivatives related in structure to 4-MTA. A number of these compounds...... of the serotonin transporter, a high affinity target for amphetamines and independent of protein tyrosine phosphatases and tubulin dynamics both of which have been previously associated with nitrostyrene-induced cell death. We demonstrate that a number of these compounds induce caspase activation, PARP cleavage...

  14. [Congestive cardiomyopathy in addiction to clobenzorex, an anorexigenic drug].

    Science.gov (United States)

    Cornaert, P; Camblin, J; Graux, P; Anaye, B; Dutoit, A; Croccel, L

    1986-04-01

    Cardiac failure caused by high doses of amphetamine-like drugs is rare. We report a case of decompensated congestive cardiomyopathy occurring in a 29 year old woman addicted to clobenzorex (Dinintel). This patient had been taking 5 to 7 capsules per day for 5 years. No other cause of cardiac failure was detected. A rapid improvement was obtained by digitalis and diuretic therapy; no further episodes of cardiac failure were observed after one year. However, the drug could not be completely withdrawn and echocardiography has shown increasing left ventricular dilatation. The possible mechanisms of amphetamine induced myocardial toxicity are discussed and the analogy with the group of adrenergic cardiomyopathies is underlined.

  15. Drug-related death in Denmark in 2007

    DEFF Research Database (Denmark)

    Simonsen, K. W.; Hansen, A. C.; Rollmann, D.

    2011-01-01

    : The number of drug-related deaths in 2007 was 226. Methadone deaths had increased since 1997 while heroin/morphine deaths decreased. In earlier studies, very few deaths from central stimulants like cocaine and amphetamines occurred (1-1.5%), but in 2007 6% of the deaths were caused by these drugs. Multiple...... drug use was common. Heroin/morphine, cocaine, amphetamine, cannabis, methadone, benzodiazepines and alcohol were included in the poly-drug use. CONCLUSION: This investigation shows stabilization in the number of fatal poisonings in drug addicts. Geographic differences were observed. Methadone...

  16. Free Drug Samples in the United States: Characteristics of Pediatric Recipients and Safety Concerns

    Science.gov (United States)

    Cutrona, Sarah L.; Woolhandler, Steffie; Lasser, Karen E.; Bor, David H.; Himmelstein, David U.; Shrank, William H.; LeLeiko, Neal S.

    2009-01-01

    OBJECTIVES Free drug samples frequently are given to children. We sought to describe characteristics of free sample recipients, to determine whether samples are given primarily to poor and uninsured children, and to examine potential safety issues. METHODS We analyzed data on 10 295 US residents Adderall (amphetamine/dextroamphetamine), and 4 medications that received new or revised black box warnings between 2004 and 2007, Elidel (pimecrolimus), Advair (fluticasone/salmeterol), Strattera (atomoxetine), and Adderall (amphetamine/dextroamphetamine). CONCLUSIONS Poor and uninsured children are not the main recipients of free drug samples. Free samples do not target the neediest children selectively, and they have significant safety considerations. PMID:18829796

  17. Myocardial infarction associated with adderall XR and alcohol use in a young man.

    Science.gov (United States)

    Jiao, Xiangyang; Velez, Sonia; Ringstad, Jennifer; Eyma, Valerie; Miller, Daniel; Bleiberg, Melvyn

    2009-01-01

    Adderall, consisting of a mixture of amphetamine salts and dextroamphetamine salts, is a prescription drug for attention deficit/hyperactivity disorder (ADHD) and narcolepsy. Labeled or unlabeled use of Adderall is gaining popularity among young children and college students. Although it is rare, Adderall use is associated with myocardial infarction and even sudden death. We report a case of a young man with acute myocardial infarction after taking 2 15-mg tablets of Adderall XR with alcohol and discuss the clinical features, diagnosis, and management of the cardiovascular effect of amphetamine-containing drugs.

  18. Patterns and Correlates of Prescription Opioid Use in OEF/OIF Veterans with Chronic Non-Cancer Pain

    Science.gov (United States)

    2011-10-01

    identify factors associated with receiving opioid prescriptions. Psychiatric disorders , including generalized anxiety disorder , panic disorder , depression...collected information regarding substance use disorder (defined as substance abuse/dependence diagnoses for alcohol, amphetamine, cannabis , cocaine, opioids...most commonly diagnosed substance use disorders were alcohol (11.8%), cannabis (3.7%), or other substance use disorder (8.8%). Opioids were prescribed to

  19. Space Flight Research Relevant to Health, Physical Education, and Recreation. With Particular Reference to Skylab’s Life Science Experiments

    Science.gov (United States)

    1979-06-01

    Essentially no changes were ob- served in reactivity of immune systems as typified by rate of RNA or DNA synthesis in small lymphocytes. Metabolic...scopolamine and d-amphetamine, and promethazine hydro- chloride and ephedrine sulfate) were effective in the prevention and treatment’of motion

  20. Locally Weighted Learning Methods for Predicting Dose-Dependent Toxicity with Application to the Human Maximum Recommended Daily Dose

    Science.gov (United States)

    2012-09-10

    pseudoephedrine 4 brompheniramine 0.4 maltose 100 ephedrine 1.67 2 dextroamphetamine 1 7 levocarnitine 49.5 12 methadyl acetate 2.33 amphetamine 1 carnitine...effects.27 However, most drugs on the market are racemic mixtures, presumably due to expenses in chiral synthesis / separation, and, in most cases