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Sample records for amphetamine methamphetamine mda

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

    Science.gov (United States)

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

    2016-08-01

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

  2. Methamphetamine, amphetamine, MDMA ('ecstasy'), MDA and mCPP modulate electrical and cholinergic input in PC12 cells.

    Science.gov (United States)

    Hondebrink, Laura; Meulenbelt, Jan; Rietjens, Saskia J; Meijer, Marieke; Westerink, Remco H S

    2012-03-01

    Reversal of the dopamine (DA) membrane transporter is the main mechanism through which many drugs of abuse increase DA levels. However, drug-induced modulation of exocytotic DA release by electrical (depolarization) and neurochemical inputs (e.g., acetylcholine (ACh)) may also contribute. We therefore investigated effects of methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA) and meta-chlorophenylpiperazine (mCPP) (1-1000 μM) on these inputs by measuring drug-induced changes in basal, depolarization- and ACh-evoked intracellular calcium concentrations ([Ca(2+)](i)) using a dopaminergic model (PC12 cells) and Fura 2 calcium imaging. The strongest drug-induced effects were observed on cholinergic input. At 0.1mM all drugs inhibited the ACh-evoked [Ca(2+)](i) increases by 40-75%, whereas ACh-evoked [Ca(2+)](i) increases were nearly abolished following higher drug exposure (1mM, 80-97% inhibition). Additionally, high MDMA and mCPP concentrations increased basal [Ca(2+)](i), but only following prior stimulation with ACh. Interestingly, low concentrations of methamphetamine or amphetamine (10 μM) potentiated ACh-evoked [Ca(2+)](i) increases. Depolarization-evoked [Ca(2+)](i) increases were also inhibited following exposure to high drug concentrations, although drugs were less potent on this endpoint. Our data demonstrate that at high drug concentrations all tested drugs reduce stimulation-evoked increases in [Ca(2+)](i), thereby probably reducing dopaminergic output through inhibition of electrical and cholinergic input. Furthermore, the increases in basal [Ca(2+)](i) at high concentrations of MDMA and mCPP likely increases dopaminergic output. Similarly, the increases in ACh-evoked [Ca(2+)](i) upon cholinergic stimulation following exposure to low concentrations of amphetamines can contribute to drug-induced increases in DA levels observed in vivo. Finally, this study shows that mCPP, which is regularly found in

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

    Science.gov (United States)

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

    2006-06-01

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

  4. Confirmation of amphetamine, methamphetamine, MDA and MDMA in urine samples using disk solid-phase extraction and gas chromatography-mass spectrometry after immunoassay screening.

    Science.gov (United States)

    Huang, Zengping; Zhang, Shaoyu

    2003-07-25

    A method using mixed phase disk solid-phase extraction (SPE) and gas chromatography-mass spectrometry (GC-MS) was developed for confirmation of amphetamine (AMP), methamphetamine (MET), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples after immunoassay screening. Disk SPE provided hydrophobic (C(18)) and strong cation-exchange (SCX) interactions. The analytes were retained on SCX functional groups in the disk and eluted with ammoniated ethyl acetate after washed with methanol. Confirmation and quantitation was exercised by selected ion monitoring using nikethamide as chromatographic standard. Recoveries of the amphetamines were between 73.0 and 104.6% with RSDs in range of 2.1-6.4% (n=3). The limits of detection were 2 ng/ml for AMP, MET and MDMA, and 4 ng/ml for MDA. Five real urine samples were tested with the method after immunoassay screening, and the results were comparable to those of traditional liquid-liquid extraction (LLE). The method was solvent-saved, simple, rapid and reliable, and the extract was cleaner than that of LLE.

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

    Science.gov (United States)

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

    2003-01-01

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

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

    DEFF Research Database (Denmark)

    Johansen, Sys Stybe; Jornil, Jakob

    2009-01-01

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

  7. Psychophysiological aspects of amphetamine-methamphetamine abuse.

    Science.gov (United States)

    Murray, J B

    1998-03-01

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

  8. 21 CFR 250.101 - Amphetamine and methamphetamine inhalers regarded as prescription drugs.

    Science.gov (United States)

    2010-04-01

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

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

    OpenAIRE

    2011-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  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. 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.

  13. Methamphetamine: Glossary

    Science.gov (United States)

    ... to treat attention deficit hyperactivity disorder (e.g., methylphenidate and amphetamines), as well as cocaine and methamphetamine. ... is methamphetamine? What is the scope of methamphetamine abuse in the United States? How is methamphetamine abused? ...

  14. Small volume liquid extraction of amphetamines in saliva.

    Science.gov (United States)

    Meng, Pinjia; Wang, Yanyan

    2010-04-15

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

  15. Amphetamines

    Science.gov (United States)

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

  16. Oral fluid with three modes of collection and plasma methamphetamine and amphetamine enantiomer concentrations after controlled intranasal l-methamphetamine administration.

    Science.gov (United States)

    Newmeyer, Matthew N; Concheiro, Marta; da Costa, Jose Luiz; Flegel, Ronald; Gorelick, David A; Huestis, Marilyn A

    2015-10-01

    Methamphetamine is included in drug testing programmes due to its high abuse potential. d-Methamphetamine is a scheduled potent central nervous system stimulant, while l-methamphetamine is the unscheduled active ingredient in the over-the-counter nasal decongestant Vicks® VapoInhaler™. No data are available in oral fluid (OF) and few in plasma after controlled Vicks® VapoInhaler™ administration. We quantified methamphetamine and amphetamine enantiomers in OF collected with two different devices and plasma via a fully validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Additionally, OF were analyzed with an on-site screening device. Sixteen participants received 7 Vicks® VapoInhaler™ doses according to manufacturer's recommendations. Specimens were collected before and up to 32 h after the first dose. No d-methamphetamine or d-amphetamine was detected in any sample. All participants had measurable OF l-methamphetamine with median maximum concentrations 14.8 and 16.1 μg/L in Quantisal™ and Oral-Eze® devices, respectively, after a median of 5 doses. One participant had measurable OF l-amphetamine with maximum concentrations 3.7 and 5.5 μg/L after 6 doses with the Quantisal™ and Oral-Eze® devices, respectively. There were no positive DrugTest® 5000 results. In the cutoff range 20-50 μg/L methamphetamine with amphetamine ≥limit of detection, 3.1-10.1% of specimens were positive; first positive results were observed after 1-4 doses. Two participants had detectable plasma l-methamphetamine, with maximum observed concentrations 6.3 and 10.0 μg/L after 2 and 5 doses, respectively. Positive OF and plasma methamphetamine results are possible after Vicks® VapoInhaler™ administration. Chiral confirmatory analyses are necessary to rule out VapoInhaler™ intake. Implementing a selective d-methamphetamine screening assay can help eliminate false-positive OF results.

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

    Science.gov (United States)

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

    2011-01-01

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

  18. Determination of amphetamine, methamphetamine, MDA and MDMA in urine samples by solid-phase microextraction and gas chromatography-mass spectrometry in selected ion monitoring%尿中苯丙胺、甲基苯丙胺、MDA和MDMA的固相微萃取和GC/MS/SIM测定

    Institute of Scientific and Technical Information of China (English)

    张绍雨; 黄增萍

    2005-01-01

    目的研究固相微萃取(SPME)用于尿中苯丙胺(AMP)、甲基苯丙胺(MET)、3,4-亚甲二氧基苯丙胺(MDA)和3,4-亚甲二氧基甲基苯丙胺(MDMA)的提取.方法样品调节至碱性和用盐饱和后用顶空SPME,内标为MET-d5.萃取纤维为100μm聚二甲基硅氧烷(PDMS).用气质联用选择离子检测(GC/MS/SIM).结果0.2μg/ml加标尿样,AMP、MET、MDA和MDMA的富集倍数分别为22,60,13和47.检出限(S/N=3)为0.4~9.5 ng/ml.线性范围为0.05~1μg/ml.0.2、0.5和1.0μg/ml加标尿样,相对回收率77.9%~112.4%,变异系数2.7%~18.0%(n=5).用该方法分析5个案件样品,和常规液液萃取结果接近.结论顶空SPME法用于尿中AMP、MET、MDA和MDMA等化合物的分析,无需有机溶剂,富集效率高,提取-富集-进样一体化,简单方便实用.

  19. Mephedrone does not damage dopamine nerve endings of the striatum, but enhances the neurotoxicity of methamphetamine, amphetamine, and MDMA.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Briggs, Denise I; Francescutti, Dina M; Sykes, Catherine E; Shah, Mrudang M; Thomas, David M; Kuhn, Donald M

    2013-04-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine stimulant drug of abuse with close structural and mechanistic similarities to methamphetamine. One of the most powerful actions associated with mephedrone is the ability to stimulate dopamine (DA) release and block its re-uptake through its interaction with the dopamine transporter (DAT). Although mephedrone does not cause toxicity to DA nerve endings, its ability to serve as a DAT blocker could provide protection against methamphetamine-induced neurotoxicity like other DAT inhibitors. To test this possibility, mice were treated with mephedrone (10, 20, or 40 mg/kg) prior to each injection of a neurotoxic regimen of methamphetamine (four injections of 2.5 or 5.0 mg/kg at 2 h intervals). The integrity of DA nerve endings of the striatum was assessed through measures of DA, DAT, and tyrosine hydroxylase levels. The moderate to severe DA toxicity associated with the different doses of methamphetamine was not prevented by any dose of mephedrone but was, in fact, significantly enhanced. The hyperthermia caused by combined treatment with mephedrone and methamphetamine was the same as seen after either drug alone. Mephedrone also enhanced the neurotoxic effects of amphetamine and 3,4-methylenedioxymethamphetamine on DA nerve endings. In contrast, nomifensine protected against methamphetamine-induced neurotoxicity. As mephedrone increases methamphetamine neurotoxicity, the present results suggest that it interacts with the DAT in a manner unlike that of other typical DAT inhibitors. The relatively innocuous effects of mephedrone alone on DA nerve endings mask a potentially dangerous interaction with drugs that are often co-abused with it, leading to heightened neurotoxicity.

  20. 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.

  1. Rapid simultaneous determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and 3,4-methylenedioxyethylamphetamine in urine by fast gas chromatography-mass spectrometry.

    Science.gov (United States)

    Klette, Kevin L; Jamerson, Matthew H; Morris-Kukoski, Cynthia L; Kettle, Aaron R; Snyder, J Jacob

    2005-10-01

    The use of fast gas chromatography-mass spectrometry (FGC-MS) was investigated to improve the efficiency of analysis of urine specimens that previously screened presumptively positive for amphetamine (AMP), methamphetamine (MAMP), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and/or 3,4 methylenedioxyethylamphetamine (MDEA) by immunoassay testing. Specimens were pretreated with basic sodium periodate, extracted using a positive-pressure manifold/cation-exchange solid-phase cartridge methodology, and derivatized using 4-carbethoxyhexafluorobutyryl chloride (4-CB). The analytical method was compared to traditional GC-MS analysis and evaluated with respect to assay chromatography, linearity, sensitivity, precision, accuracy, and reproducibility. The limits of detection were 62.5 ng/mL for MDA and 31.25 ng/mL for AMP, MAMP, MDMA, and MDEA. All of the target analytes were linear to 12,000 ng/mL with the exception of MAMP which was linear to 10,000 ng/mL. The intra-assay precision of a 500 ng/mL multiconstituent control (n=15) ranged from 522.6 to 575.9 ng/mL with a coefficient of variation of less than 3.8%. Authentic human urine specimens (n=187) previously determined to contain the target analytes were re-extracted and analyzed by both FGC-MS and the currently utilized GC-MS method. No significant differences in specimen concentration were observed between these analytical methods. No interferences were seen when the performance of the FGC-MS method was challenged with ephedrine, pseudoephedrine, phenylpropanolamine, and phentermine. When compared to traditional GC-MS analysis, FGC-MS analysis provided a dramatic reduction in retention time for amphetamine (1.8 min vs. 4.12 min). For example, the FGC-MS method reduced overall run time for a batch of 56 specimens from 12.0 h to 7.25 h. This reduction in analysis time makes FGC-MS an attractive alternative to traditional GC-MS by allowing a laboratory greater flexibility in the purchase

  2. Performance characteristics of selected immunoassays for preliminary test of 3,4-methylenedioxymethamphetamine, methamphetamine, and related drugs in urine specimens.

    Science.gov (United States)

    Hsu, Jui; Liu, Chiareiy; Liu, C P; Tsay, Wen-Ing; Li, Jih-Heng; Lin, Dong-Liang; Liu, Ray H

    2003-10-01

    Eight commercially available immunoassays for amphetamines (DRI Amphetamines, CEDIA DAU Amphetamines-Semiquantitative, EMIT d.a.u. Monoclonal Amphetamine/Methamphetamine, Synchron CX Systems AMPH, TDx/TDxFLx Amphetamine/Methamphetamine II, CEDIA Amphetamines/Ecstasy, COBAS INTEGRA Amphetamines, and Abuscreen((R)) OnLine HS Amphetamine/MDMA) are evaluated for their effectiveness in serving as the preliminary test methodology for the analysis of 3,4-methylenedioxymethamphetamine/3,4-methylenedioxyamphetamine (MDMA/MDA) and methamphetamine/amphetamine (MA/AM). Standard solutions (in urine matrix) of MDMA, MDA, MA, and AM are used to determine these immunoassays' reactivities (or cross-reactivities) toward these compounds of interest. Case specimens containing MDMA/MDA and MA/AM are also used to study the correlations of the apparent immunoassay MDMA (or MA) concentrations and the gas chromatographic-mass spectrometric concentrations of these compounds. Data resulting from this study suggest that CEDIA Amphetamines/Ecstasy can best predict the concentrations of MDMA and MA in case specimens and can also detect the presence of MDMA at low levels, whereas Abuscreen OnLine HS Amphetamine/MDMA can detect both MDMA and MA at low concentrations.

  3. Amphetamine

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2012-03-01

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

  5. Determination of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxyethylamphetamine, and 3,4-methylenedioxymethamphetamine in urine by online solid-phase extraction and ion-pairing liquid chromatography with detection by electrospray tandem mass spectrometry.

    Science.gov (United States)

    Wu, Ti-Yu; Fuh, Ming-Ren

    2005-01-01

    A method using an online solid-phase extraction (SPE) and ion-pairing liquid chromatography with electrospray tandem mass spectrometry (LC/ES-MS/MS) was developed for determination of amphetamine (Amp), methamphetamine (mAmp), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxyethylamphetamine (MDEA), and 3,4-methylenedioxymethamphetamine (MDMA) in urine samples. A SPE cartridge column with both hydrophilic and lipophilic functions was utilized for online extraction. A reversed-phase C18 LC column was employed for LC separation and MS/MS was used for detection. Trifluoroacetic acid was added to the mobile phase as an ion-pairing reagent. This method was fully automated and the extraction and analysis procedures were controlled by a six-port switch valve. Recoveries ranging from 85-101% were measured. Good linear ranges (10-500 ng/mL) for Amp and mAmp were determined. For MDA, MDMA and MDEA, dual linear ranges were obtained from 5-100 and 100-500 ng/mL, respectively. The detection limit of each analytical compound, based on a signal-to-noise ratio of 3, ranged from 1-3 ng/mL. The applicability of this newly developed method was examined by analyzing several urine samples from drug users. Good agreement was obtained between the results from this method and a literature GC/MS method.

  6. Methamphetamine

    Science.gov (United States)

    ... and Over-the-Counter Medications Stimulant ADHD Medications: Methylphenidate and Amphetamines Synthetic Cannabinoids Synthetic Cathinones ("Bath Salts") Effects of Drug Abuse Comorbidity: Addiction and Other Mental Disorders Drug Use ...

  7. Methamphetamine

    Science.gov (United States)

    ... similar to amphetamine [a drug used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy, a sleep disorder]. Learn more Also more about: Health Effects Statistics and Trends Swipe left or right to ...

  8. Estimation of the measurement uncertainty by the bottom-up approach for the determination of methamphetamine and amphetamine in urine.

    Science.gov (United States)

    Lee, Sooyeun; Choi, Hyeyoung; Kim, Eunmi; Choi, Hwakyung; Chung, Heesun; Chung, Kyu Hyuck

    2010-05-01

    The measurement uncertainty (MU) of methamphetamine (MA) and amphetamine (AP) was estimated in an authentic urine sample with a relatively low concentration of MA and AP using the bottom-up approach. A cause and effect diagram was deduced; the amount of MA or AP in the sample, the volume of the sample, method precision, and sample effect were considered uncertainty sources. The concentrations of MA and AP in the urine sample with their expanded uncertainties were 340.5 +/- 33.2 ng/mL and 113.4 +/- 15.4 ng/mL, respectively, which means 9.7% and 13.6% of the concentration gave an estimated expanded uncertainty, respectively. The largest uncertainty originated from sample effect and method precision in MA and AP, respectively, but the uncertainty of the volume of the sample was minimal in both. The MU needs to be determined during the method validation process to assess test reliability. Moreover, the identification of the largest and/or smallest uncertainty source can help improve experimental protocols.

  9. Phentermine interference and high L-methamphetamine concentration problems in GC-EI-MS SIM Analyses of R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride-derivatized amphetamines and methamphetamines†.

    Science.gov (United States)

    Hamilton, Theron J; Qui, Harry Z; Dozier, Katherine V R; Fuller, Zachary J

    2014-09-01

    In order to achieve chromatographic separation, urine samples shown to be initially positive for amphetamines and methamphetamines in US Department of Defense immunoassays are derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-(-)-MTPA) prior to gas chromatography-electron impact-mass spectrometry (GC-EI-MS) analysis. Phentermine, a member of the phenethylamine class of drugs and a common appetite suppressant, interferes with GC-EI-MS assays of R-(-)-MTPA-derivatized d-amphetamine, degrading the chromatography of the internal standard and analyte ions and skewing concentration calculations. Additionally, when specimens with high concentrations of l-methamphetamine are derivatized with R-(-)-MTPA, signal peaks have the potential to be misidentified by integration software as d-methamphetamine. We have found that replacing R-(-) MTPA with (S)-(+)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride reduces phentermine interference problems related to internal standard chromatography, reduces the possibility of concentrated l-methamphetamine peaks being misidentified by integration software, improves resolution of d-methamphetamine in the presence of high l-methamphetamine concentrations, and is a cost-neutral change that can be applied to current amphetamines GC-EI-MS methods without the need for method modification.

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

    Science.gov (United States)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2003-06-05

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

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

    OpenAIRE

    Medhus, Sigrid

    2014-01-01

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

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

    Science.gov (United States)

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

    1999-12-10

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

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

    Science.gov (United States)

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

    2009-12-15

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

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

    Science.gov (United States)

    Casari, C; Andrews, A R

    2001-09-01

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

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

    Science.gov (United States)

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

    2004-01-01

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

  17. HPLC法测定甲基苯丙胺与苯丙胺%Detecting Methamphetamine and Amphetamine with High Performance Liquid Chromatography

    Institute of Scientific and Technical Information of China (English)

    傅强; 廖林川; 陈礼莉; 颜有仪; 杨林; 侯俊红; 陈渝

    2007-01-01

    目的 建立甲基苯丙胺(methamphetamine,MA)和苯丙胺(amphetamine,AMP)的反相高效液相色谱测定方法.方法 采用C18柱,以甲醇-磷酸盐缓冲液为流动相,流速1.0 mL/min,检测波长为215 nm,同时收集190~360 nm的紫外光谱图,并以此与保留时间作为定性依据.在定性的基础上,建立定量检测方法,并对方法进行评价研究.结果 所建方法能良好分离MA和AMP,结合判断依据能准确定性;MA在1.4~270 μg/mL浓度范围内线性关系良好,R2=1,日内标准偏差(RSD)与日间RSD均<2.4%,检出限为0.73 μg/mL,平均加样回收率为102.5%;AMP在0.9~580 μg/mL浓度范围内线性关系良好,R2=0.9999,日内RSD与日间RSD均<2.3%,检出限为0.52 μg/mL,平均加样回收率为101.7%.结论 此方法简便、快速、准确,适用于MA与AMP的检测.

  18. Toxicity of amphetamines: an update.

    Science.gov (United States)

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

    2012-08-01

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

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

    Science.gov (United States)

    Zhu, Dan; Meng, Pinjia; He, Hongyuan

    2007-01-01

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

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

    Science.gov (United States)

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

    2010-08-01

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

  1. 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.

  2. 甲基苯丙胺对大鼠脑组织中NO,SOD和MDA的影响%CHANGE OF NO,SOD AND MDA IN METHAMPHETAMINE-TREATED RAT BRAIN AND THEIR CORRELATION

    Institute of Scientific and Technical Information of China (English)

    陈汉; 王慧君; 李学锋; 邱平明

    2007-01-01

    目的:观察甲基苯丙胺(methamphetamine,MA)所致大鼠脑组织中一氧化氮(NO)、超氧化物歧化酶(SOD)、丙二醛(MDA)的变化.方法:建立 MA给药模型;实验组给予 MA,对照组给予等量生理盐水,观察两组脑组织中 NO,SOD和MDA的变化及 3者之间的相互关系.结果:实验组脑组织海马区和纹状体区中 NO,MDA 含量上升,SOD 含量下降,与对照组相比差异有显著性(P<0.01).结论:MA可导致大鼠脑中 NO含量上升,SOD活性下降,MDA含量升高.说明超氧化基参与了 MA的神经毒性作用,这可能是MA引起中枢神系统损伤的重要机制.

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

    Science.gov (United States)

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

    2006-04-01

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

  4. Novel biomarkers of prenatal methamphetamine exposure in human meconium

    Science.gov (United States)

    Gray, Teresa R.; Kelly, Tamsin; LaGasse, Linda L.; Smith, Lynne M.; Derauf, Chris; Haning, William; Grant, Penny; Shah, Rizwan; Arria, Amelia; Strauss, Arthur; Lester, Barry M.; Huestis, Marilyn A.

    2008-01-01

    Meconium analysis can detect fetal exposure to drugs taken by the mother during pregnancy. Methamphetamine and amphetamine have previously been observed in meconium of methamphetamine-exposed neonates; the presence of other metabolites has not been investigated. Detection of such analytes may lead to more sensitive identification and, thus improved medical treatment of affected infants. Methods and Materials Forty-three methamphetamine-positive meconium specimens were analyzed for newly identified methamphetamine biomarkers, p-hydroxymethamphetamine, p-hydroxyamphetamine, and norephedrine. Due to methamphetamine adulteration in illicit ecstasy and to simultaneously monitor 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine prenatal exposure, MDMA, its metabolites and related sympathomimetic amines were assayed. Results Methamphetamine, amphetamine and unconjugated p-hydroxymethamphetamine were the most prevalent and abundant analytes present in meconium; however, unconjugated p-hydroxyamphetamine and norephedrine also were identified. Discussion It is possible that one of these additional analytes could be important for predicting toxicity or maternal or neonatal outcome measures in fetuses exposed to methamphetamine at specific gestational ages or with different metabolic capabilities. Although these new biomarkers were present in lower concentrations than methamphetamine and amphetamine in the meconium of previously confirmed specimens, additional research will determine if inclusion of these analytes can increase identification of methamphetamine-exposed neonates. Conclusion Novel methamphetamine biomarker concentrations were characterized in meconium of infants exposed in utero to methamphetamine. PMID:19125148

  5. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection.

    Science.gov (United States)

    Nakamoto, Akihiro; Nishida, Manami; Saito, Takeshi; Kishiyama, Izumi; Miyazaki, Shota; Murakami, Katsunori; Nagao, Masataka; Namura, Akira

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d(5) was used as an internal standard. The linear ranges were 0.01-5.0 microg mL(-1) for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 microg mL(-1) for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation > or = 0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 microg mL(-1) of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio > or = 3) in urine was 5 ng mL(-1) for MA and MDMA and 10 ng mL(-1) for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

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

    Science.gov (United States)

    Lott, S; Musshoff, F; Madea, B

    2012-09-10

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

  7. Methamphetamine (Meth)

    Science.gov (United States)

    ... Enter Search Term(s): Teens / Drug Facts / Methamphetamine (Meth) Methamphetamine (Meth) Street names: Crank, Crystal, Speed Print What is methamphetamine (meth)? Also known as: Meth, Speed, Chalk, and ...

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

    Science.gov (United States)

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

    2006-01-01

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

  9. 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.

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

    Science.gov (United States)

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

    2011-04-01

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

  11. 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.

  12. 3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

    Energy Technology Data Exchange (ETDEWEB)

    McKenna, D.J.; Guan, X.M.; Shulgin, A.T. (Department of Neurology Neurological Sciences, Stanford University Medical Center, CA (USA))

    1991-03-01

    The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, also show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.

  13. Comparison of five derivatizing agents for the determination of amphetamine-type stimulants in human urine by extractive acylation and gas chromatography-mass spectrometry.

    Science.gov (United States)

    Dobos, Adrienn; Hidvégi, Elod; Somogyi, Gábor Pál

    2012-06-01

    Five acylation reagents have been compared for use as derivatizing agents for the analysis of amphetamine-type stimulants (ATS) in urine by gas chromatography-mass spectrometry (GC-MS). The evaluated reagents were heptafluorobutyric anhydride, pentafluoropropionic anhydride, trifluoroacetic anhydride, acetic anhydride (AA) and N-methyl-bis(trifluoroacetamide). The ATS included amphetamine, methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyethylamphetamine (MDEA). A mixture of the ATS was added to urine (1 mL) followed by KOH solution and saturated NaHCO(3) solution. The sample was then extracted with dichloromethane and the derivatizing agent and 2 µL were injected into the GC-MS instrument. The derivatizing agents were compared with reference to the signal-to-noise (S/N) ratios, peak area values, relative standard deviations (RSDs), linearities, limits of detection (LODs) and selectivities. The acetic anhydride proved to be the best according to the S/N ratio and peak area results for amphetamine, MA, MDMA and MDEA. The best RSD values of peak areas and of S/N ratios at 3 µg/mL were also given by AA in cases of MDA, MDMA and MDEA. At 20 µg/mL, the lowest RSD values of peak areas for MDA and the lowest RSD values of S/N ratios for MA, MDA, MDMA and MDEA were again given by AA. Additionally, the highest correlation coefficients for MA, MDA, MDMA and MDEA and the lowest LOD results for MA, MDMA and MDEA were produced by AA.

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

    Science.gov (United States)

    Rojek, Sebastian; Kłys, Małgorzata; Konopka, Tomasz

    2009-01-01

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

  15. Integration of GC/EI-MS and GC/NCI-MS for simultaneous quantitative determination of opiates, amphetamines, MDMA, ketamine, and metabolites in human hair.

    Science.gov (United States)

    Wu, Ya-Hsueh; Lin, Keh-Liang; Chen, Su-Chin; Chang, Yan-Zin

    2008-07-15

    In this paper, the possibility of using a multiple ionization mode approach of GC/MS was developed for the simultaneous hair testing of common drugs of abuse in Asia, including amphetamines (amphetamine, AP; methamphetamine, MA; methylenedioxy amphetamine, MDA; methylenedioxy methamphetamine, MDMA; methylenedioxy ethylamphetamine, MDEA), ketamine (ketamine, K; norketamine, NK), and opiates (morphine, MOR; codeine, COD; 6-acetylmorphine, 6-AM). This strategy integrated the characteristics of gas chromatography-mass spectrometry (GC-MS) using electron impact ionization (EI) and negative chemical ionization (NCI). Hair samples (25 mg) were washed, cut, and incubated overnight at 25 degrees C in methanol-trifluoroacetic acid (methanol-TFA). The samples were extracted by solid phase extraction (SPE) procedure, derivatized using heptafluorobutyric acid anhydride (HFBA) at 70 degrees C for 30 min, and the derivatives analyzed by GC-MS with EI and NCI. The limit of detection (LOD) with GC/EI-MS analysis obtained were 0.03 ng/mg for AP, MA, MDA, MDMA, and MDEA; 0.05 ng/mg for K, NK, MOR, and COD; and 0.08 ng/mg for 6-AM. The LOD of GC/NCI-MS analysis was much lower than GC/EI-MS analysis. The LOD obtained were 30 pg/mg for AP and MDA in GC/EI-MS and 2 pg/mg in GC/NCI-MS. Therefore, the sensitivity of AP and MDA in GC/NCI-MS was improved from 15-fold compared with EI. The sensitivity of AP, MA, MDA, MDMA, MDEA, MOR, and COD was improved from 15- to 60-fold compared with EI. In addition, the sensitivity of 6-AM increased 8-fold through selection of m/z 197 for the quantitative ion. Moreover, K and NK could dramatically improve their sensitivity at 200- and 2000-fold. The integration of GC/EI-MS and GC/NCI-MS can obtain the high sensitivity and complementary results of drugs of abuse in hair. Six hair samples from known drug abusers were examined by this new strategy. These results show that integrating the characteristics of GC/EI-MS and GC/NCI-MS were not only enhancement of

  16. Possible role of exercise on methamphetamine dependence management

    OpenAIRE

    Morais, António Pedro Delgado

    2015-01-01

    Trabalho final de mestrado integrado em Medicina (Farmacologia), apresentado à Faculdade de Medicina da Universidade de Coimbra. An estimated 34,4 million people has consumed amphetamine-type stimulants over the last evaluated year (2012), which alerts for the high prevalence of this drug group, being the second most abused drug group in several countries. Methamphetamine is the primary drug within amphetamine-type stimulants, being highly used in the United States of America, Central and ...

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

    OpenAIRE

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

    2016-01-01

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

  18. Methamphetamine Pills

    Science.gov (United States)

    ... symptoms of prolonged meth use are characterized by paranoia, hallucinations, repetitive behavior patterns, and delusions of parasites ... violent, aggressive behavior is usually coupled with extreme paranoia. New research shows that those who use methamphetamine ...

  19. Methamphetamine overdose

    Science.gov (United States)

    ... form of the drug is used to treat narcolepsy and attention deficit hyperactivity disorder (ADHD). This weaker ... name Desoxyn. It is sometimes used to treat narcolepsy. Adderall, a brand name drug containing amphetamine, is ...

  20. 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.

  1. 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).

  2. Monolithic silica spin column extraction and simultaneous derivatization of amphetamines and 3,4-methylenedioxyamphetamines in human urine for gas chromatographic-mass spectrometric detection

    Energy Technology Data Exchange (ETDEWEB)

    Nakamoto, Akihiro [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nishida, Manami [Hiroshima University Technical Center, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Saito, Takeshi [Department of Emergency and Critical Care Medicine, Tokai University School of Medicine, Shimokasuya 143, Isehara, Kanagawa 259-1143 (Japan); Kishiyama, Izumi; Miyazaki, Shota [GL Sciences Inc., Sayamagahara 237-2, Iruma, Saitama 358-0032 (Japan); Murakami, Katsunori [Scientific Investigation Laboratory, Hiroshima Prefectural Police Headquarters, Kohnan 2-26-3, Naka-ku, Hiroshima 730-0825 (Japan); Nagao, Masataka [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan); Namura, Akira, E-mail: namera@hiroshima-u.ac.jp [Department of Forensic Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551 (Japan)

    2010-02-19

    A simple, sensitive, and specific method with gas chromatography-mass spectrometry was developed for simultaneous extraction and derivatization of amphetamines (APs) and 3,4-methylenedioxyamphetamines (MDAs) in human urine by using a monolithic silica spin column. All the procedures, such as sample loading, washing, and elution were performed by centrifugation. APs and MDAs in urine were adsorbed on the monolithic silica and derivatized with propyl chloroformate in the column. Methamphetamine-d{sub 5} was used as an internal standard. The linear ranges were 0.01-5.0 {mu}g mL{sup -1} for methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA) and 0.02-5.0 {mu}g mL{sup -1} for amphetamine (AP) and 3,4-methylenedioxyamphetamine (MDA) (coefficient of correlation {>=}0.995). The recovery of APs and MDAs in urine was 84-94%, and the relative standard deviation of the intra- and interday reproducibility for urine samples containing 0.1, 1.0, and 4.0 {mu}g mL{sup -1} of APs and MDAs ranged from 1.4% to 13.6%. The lowest detection limit (signal-to-noise ratio {>=} 3) in urine was 5 ng mL{sup -1} for MA and MDMA and 10 ng mL{sup -1} for AP and MDA. The proposed method can be used to perform simultaneous extraction and derivatization on spin columns that have been loaded with a small quantity of solvent by using centrifugation.

  3. Mind Over Matter: Methamphetamine

    Science.gov (United States)

    ... Term(s): Teachers / NIDA Teaching Guide / Mind Over Matter Teaching Guide and Series / Methamphetamine Print Mind Over Matter: Methamphetamine (Meth) Order Free Publication in: English Spanish Download PDF 739.54 KB Methamphetamine comes ...

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

    Science.gov (United States)

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

    2009-09-01

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

  5. Simultaneous analysis of six amphetamines and analogues in hair, blood and urine by LC-ESI-MS/MS. Application to the determination of MDMA after low ecstasy intake.

    Science.gov (United States)

    Chèze, Marjorie; Deveaux, Marc; Martin, Claire; Lhermitte, Michel; Pépin, Gilbert

    2007-08-06

    A rapid and sensitive method using LC-MS/MS triple stage quadrupole for the determination of traces of amphetamine (AP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"), 3,4-methylenedioxyethamphetamine (MDEA), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine (MBDB) in hair, blood and urine has been developed and validated. Chromatography was carried out on an Uptisphere ODB C(18) 5 microm, 2.1 mm x 150 mm column (Interchim, France) with a gradient of acetonitrile and formate 2 mM pH 3.0 buffer. Urine and blood were extracted with Toxitube A (Varian, France). Segmented scalp hair was treated by incubation 15 min at 80 degrees C in NaOH 1M before liquid-liquid extraction with hexane/ethyl acetate (2/1, v/v). The limits of quantification (LOQ) in blood and urine were at 0.1 ng/mL for all analytes. In hair, LOQ was urine; in the range 5-500 pg/mg for MA, MDMA, MDEA and MBDB, and 20-500 pg/mg for AP and MDA. Inter-day precisions were urine at 1 and 50 ng/mL and urine was collected a few hours after (T+12h) and tested positive to amphetamines by immunoassay by a clinical laboratory. Blood and urine were sampled for forensic purposes at day 8 (D+8) and scalp hair at day 60 (D+60). No MDMA was detected in blood, but urine and hair were tested positive, respectively at 0.42 ng/mL and at 22 pg/mg in hair only in the segment corresponding to the period of the offence, while no MDA was detectable. This method allows the detection of MDMA up to 8 days in urine after single intake.

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

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

    2011-07-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

    Crooks, C Richard; Brown, Sue

    2010-03-01

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

  10. Amphetamine derivative related deaths.

    Science.gov (United States)

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

    1997-02-28

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

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

    Directory of Open Access Journals (Sweden)

    Bramness Jørgen G

    2012-12-01

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

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

    Science.gov (United States)

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

    2000-05-12

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

    Verstraete, Alain G; Heyden, Fien V

    2005-01-01

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

  15. Stereoselective method development and validation for determination of concentrations of amphetamine-type stimulants and metabolites in human urine using a simultaneous extraction-chiral derivatization approach.

    Science.gov (United States)

    Wan Raihana, W A; Gan, S H; Tan, S C

    2011-01-01

    Amphetamine-type stimulants (ATS) are a group of chiral amine drugs which are commonly abused for their sympathomimetic and stimulant properties. ATS are extensively metabolised by hepatic cytochrome P450 enzymes. As metabolism of ATS has been shown to be highly stereospecific, stereoselective analytical methods are essential for the quantitative determination of ATS concentrations for both in vivo and in vitro studies of ATS metabolism. This paper describes a new stereoselective method for the simultaneous determination of amphetamine (AM), methamphetamine (MA), 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 4-hydroxy-3-methoxyamphetamine (HMA), 3,4-hydroxymethamphetamine (HHMA) and 3,4-hydroxyamphetamine (HHA) in human urine samples validated according to the United States Food and Drug Administration guidelines. In this method, analytes are simultaneously extracted and derivatized with R-(-)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride (R-MTPCl) as the chiral derivatization reagent. Following this, the analytes were subjected to a second derivatization with N-methyl-N-trimethylsilyltrifluoroacetamide (MSTFA) which targets the hydroxyl groups present in HMMA, HMA, HHMA and HHA. The derivatized analytes were separated and quantified using gas chromatography-mass spectrometry (GC-MS). The method was evaluated according to the established guidelines for specificity, linearity, precision, accuracy, recovery and stability using a five-day protocol. Intra-day precision ranged from 0.89 to 11.23% RSD whereas inter-day precision was between 1.03 and 12.95% RSD. Accuracy values for the analytes ranged from -5.29% to 13.75%. Limits of quantitation were 10 μg/L for AM, MA, MDMA, HMA and HMMA and 2μg/L for MDA, HMA and HHA. Recoveries and stability values were also within accepted values. The method was applied to authentic ATS-positive samples.

  16. 分子印迹固相萃取法在血中苯丙胺类毒品分析中的应用%Application of molecularly imprinted solid-phase extraction for separating and assaying amphetamines in blood samples

    Institute of Scientific and Technical Information of China (English)

    常靖; 朱军; 邸玉敏; 张雷萍; 崔巍; 郝红霞; 于忠山

    2011-01-01

    Objecive A method for extraction of amphetamines in blood samples using molecularly imprinted solid phase extraction and gas chromatography-mass spectrometry(GC/MS). Methods Human blood samples were spiked with amphetamine,methamphetamine, MDA and MDMA ,and diluted with 4:1 (v/v)with 10mmol/L ammonium acetate buffer( pH8.0); activating the MIP column with 1 mL methanol and 1mL 10mmol/L ammonium acetate( pH8. 0); Washing the impurities using 2 1 mL water, 1 mL 60/40 MeCN/water and 1 mL 1% HAc in MeCN; Elute the amphetamine drugs with 2 1mL 1% formic acid in methanol, then evaporate under nitrogen to dryness and reconstitute with 100μ L methanol prior to GC/MS analysis. Results The recoveries obtained with this method for amphetamine drugs are more than 90%. The linear range was 20 ~ 5000ng/mL with correlation coefficients between 0. 995 7 and 0. 998 9. The limits of detection were 20ng/mL for amphetamine ( AM ) , 16ng/mL methamphetamine ( MA ), 30ng/mL methylenedioxyamphetamine (MDA) and methylened ioxy methamp hetamine(MDMA) ,The limits of quantitative were 10ng/mL for AM,8ng/mL for methamphetamine(MAM), 15ng/mL for MDA and MDMA. Conclusion Recoveries are higher,impurities were less. The method could be applied for simultaneous determination of trace amphetamines in biological specimens.%目的 建立分子印迹固相萃取(MISPE)、GC/MS分析方法,用于血液中苯丙胺类毒品检测.方法 10mmol/L醋酸铵缓冲液(pH8.0)4倍稀释空白添加血液,1mL甲醇,1mL 10mmol/L醋酸铵缓冲液(pH8.0)活化苯丙胺类分子印迹固相萃取柱;2×1mL去离子水、1mL 60%的乙腈去离子水、1mL 1%醋酸乙腈洗涤杂质;2×1mL 1%甲酸/甲醇洗脱,洗脱液挥干定容,经GC/NPD、GC/MS分析检测.结果 各种苯丙胺类毒品回收率均在90%以上,在20~5000ng/mL浓度范围内线性关系良好,r2为0.9957~0.9989,LOQ在16~30ng/mL之间,LOD在8~15ng/mL之间.结论 本方法回收率高,净化效果显著,稳定性好,杂质干

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

    Science.gov (United States)

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

    2008-10-01

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

  18. Substance use -- amphetamines

    Science.gov (United States)

    ... this case, they are known as street, or recreational drugs, and using them can lead to addiction. This ... especially methamphetamine, have a high chance of getting HIV and hepatitis B and C . This can be ...

  19. On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

    Science.gov (United States)

    Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

    2012-02-15

    A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs.

  20. Crystal methamphetamine, its analogues, and HIV infection: medical and psychiatric aspects of a new epidemic.

    Science.gov (United States)

    Urbina, Antonio; Jones, Kristina

    2004-03-15

    The use of the recreational drug crystal methamphetamine among younger homosexual men is expanding, and with it, unsafe sex behaviors that increase the transmission of human immunodeficiency virus (HIV). This article reviews available literature on the medical and psychiatric morbidities associated with methamphetamine abuse in HIV-infected patients. Medical complications include hypertension, hyperthermia, rhabdoymyolysis, and stroke. One fatal case of ingestion of methamphetamine with HIV medication has been documented. Two fatal cases of ingestion of HIV medication with the amphetamine analogue n-methyl-3,4 methylenedioxymethamphetamine (MDMA, or "ecstasy") have also been reported. Some molecular researchers suggest that dopaminergic systems are vulnerable to the combined neurotoxicity of HIV infection and methamphetamine. Population surveys indicate high rates of HIV infection among methamphetamine abusers and high rates of unprotected anal intercourse during drug intoxication. Intoxication can sometimes produce paranoia, auditory hallucinations, and, occasionally, violent behavior. Amphetamine withdrawal commonly results in symptoms of depression. Methamphetamine is a new challenge related to treatment and prevention of HIV infection.

  1. Methamphetamine Related Radiculopathy: Case Series and Review of Literature

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    Mohsen Foroughipour

    2013-06-01

    Full Text Available Background: Peripheral nervous injury and neuromuscular complications from methamphetamine abuse has not been reported. The mechanism is not yet identified. Methods: Eight patients with lower extremity weakness following methamphetamine abuse were reported during December 2009 to May 2010. Results: Patients presented with lower extremity weakness. All patients were co-abusers of methamphetamine and opioids. Other clinical manifestations comprised of distal paresthesia of the lower extremities with progression to proximal portions, with minimal sensory involvement in the distal of the lower extremities. Electrodiagnostic findings were consistent with lumbosacral Radiculopathy. Vital signs were unremarkable and all laboratory tests were within normal limits. Follow-up examination after three months showed improvement of weakness in 3 patients. Conclusion: For patients with a history of illicit drug abuse and acute neuromuscular weakness, methamphetamine or heroin toxicity should be taken into account. Hence, urine morphine and amphetamine/ methamphetamine tests should be performed and serum lead and thallium levels should be evaluated. In addition, rhabdomyolysis and myoglobinuria should be worked up.

  2. The neurotoxicity of amphetamines during the adolescent period.

    Science.gov (United States)

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

    2015-04-01

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

  3. 分子印迹固相萃取-高效液相色谱法测定尿液中甲基苯丙胺和苯丙胺%Simultaneous determination of methamphetamine and amphetamine in urine by high-performance liquid chromatography with molecularly imprinted solid-phase extraction

    Institute of Scientific and Technical Information of China (English)

    朱波; 陈琦君; 金米聪

    2012-01-01

    目的:建立快速、准确的尿液中甲基苯丙胺(MA)及其代谢产物苯丙胺(AMP)的分子印迹固相萃取( MISPE)高效液相色谱测定方法.方法:尿液与10 mmol/L醋酸铵缓冲液(pH 8.0)混合后离心分离(8000 rpm),采用预先活化过的分子印迹固相萃取柱净化,以醋酸/乙腈溶液洗脱,在XBridge RP18色谱柱上,以甲醇-乙腈-水溶液( 15∶ 30∶55,V/V/V)为流动相,采用210 nm波长进行检测.结果:MA和AMP的加标回收率在88.5% ~97.0%范围,其相对标准偏差均小于5.0%,在0.05 mg/L~15.0 mg/L范围呈现良好的线性,其回归系数大于0.999,检出限(LODs)分别为0.005 mg/L和0.01 mg/L.结论:本方法回收率高,净化效果显著,稳定性好,杂质干扰少,可满足临床吸毒病人尿液中MA和AMP的检测要求.%Objective:To develop a method for the simultaneous determination of methamphetamine (MA) and amphetamine ( AMP) in urine by high - performance liquid chromatography with molecularly imprinted solid - phase extraction (MISPE). Methods; After the urine samples were mixed with 10 mmol/L ammonium acetate buffer ( pH8.0) and centrifuged at 8000 rpm, the clean up procedure was optimized on an activating molecularly imprinted solid - phase extraction cartridge and the elution was carried by acetate acid/ acetonitrile. The separation was performed on an XBridge RP18 column by a mobile phase consisting of methanol — acetonitrile - water ( 15: 30:55, V/ V/V). Detection was carried out by an ultraviolet detector at 210 nm. Results; Calibration curves of MA and AMP were linear within the range of 0.05 mg/L ~15.0 mg/L with correlation coefficients of more than 0. 999. The limits of detection (LODs) were 0. 005 mg/L and 0. 01 mg/L for MA and AMP, respectively. The extraction recoveries were between 88.5% ~97.0% , and the RSDs were less than 5.0%. Conclusion; This developed method is simple , sensitive and accurate. It is suitable for the detection of MA and AMP residues in

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

    Science.gov (United States)

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

    2012-03-01

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

  5. Amphetamines and Sports Performance.

    Science.gov (United States)

    Cooter, G. Rankin

    1980-01-01

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

  6. Determination of MDMA and MDA in rat urine by semi-micro column HPLC-fluorescence detection with DBD-F and their monitoring after MDMA administration to rat.

    Science.gov (United States)

    Wada, Mitsuhiro; Nakamura, Shinichi; Tomita, Mamoru; Nakashima, Mihoko N; Nakashima, Kenichiro

    2005-01-01

    A simultaneous semi-micro column HPLC method with fluorescence detection of abused drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), amphetamine (AP) and methamphetamine (MP) in rat urine was examined by using 4-(N,N-dimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) as a labelling reagent and alpha-phenylethylamine as an internal standard (IS). A sample (50 microL) of rat urine was added to 5 microL IS and 100 microL 100 mmol/L borate buffer (pH 12) and extracted with 1.5 mL n-hexane. After evaporation, 50 microL 75 mmol/L borate buffer (pH 8.5) and 50 microL 20 mmol/L DBD-F in CH3CN were added to the residue and mixed well. The resultant solution was heated for 20 min at 80 degrees C and then cooled in an ice bath. A good separation of DBD-derivatives could be achieved within 45 min using a semi-micro ODS column with an eluent of CH3CN/CH3OH/10 mmol/L imidazole-HNO3 buffer (pH 7.0) (= 45:5:50, v/v/v %). The DBD derivatives were monitored at 565 nm with an excitation at 470 nm. The calibration curves showed good linearity (r = 0.997) with 0.5-15 ng/mL detection limits at a S/N ratio of 3. MDMA and MDA in rat urine could be monitored for 15 h after a single administration of MDMA to rat (2.0 mg/kg, i.p.). The concentrations for MDMA and MDA (n = 3) were 0.13-160.1 and 0.17-10.9 microg/mL, respectively.

  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. Research Reports: Methamphetamine

    Science.gov (United States)

    ... abuse threatens whole communities, causing new waves of crime, unemployment, child neglect or abuse, and other social ills. A 2009 report from the RAND Corporation noted that methamphetamine abuse cost the Nation approximately $23.4 billion in 2005. ...

  9. Gray-matter volume, midbrain dopamine D2/D3 receptors and drug craving in methamphetamine users.

    Science.gov (United States)

    Morales, A M; Kohno, M; Robertson, C L; Dean, A C; Mandelkern, M A; London, E D

    2015-06-01

    Dysfunction of the mesocorticolimbic system has a critical role in clinical features of addiction. Despite evidence suggesting that midbrain dopamine receptors influence amphetamine-induced dopamine release and that dopamine is involved in methamphetamine-induced neurotoxicity, associations between dopamine receptors and gray-matter volume have been unexplored in methamphetamine users. Here we used magnetic resonance imaging and [(18)F]fallypride positron emission tomography, respectively, to measure gray-matter volume (in 58 methamphetamine users) and dopamine D2/D3 receptor availability (binding potential relative to nondisplaceable uptake of the radiotracer, BPnd) (in 31 methamphetamine users and 37 control participants). Relationships between these measures and self-reported drug craving were examined. Although no difference in midbrain D2/D3 BPnd was detected between methamphetamine and control groups, midbrain D2/D3 BPnd was positively correlated with gray-matter volume in the striatum, prefrontal cortex, insula, hippocampus and temporal cortex in methamphetamine users, but not in control participants (group-by-midbrain D2/D3 BPnd interaction, Pmidbrain D2/D3 BPnd and methamphetamine craving was not detected. Lower midbrain D2/D3 BPnd may increase vulnerability to deficits in gray-matter volume in mesocorticolimbic circuitry in methamphetamine users, possibly reflecting greater dopamine-induced toxicity. Identifying factors that influence prefrontal and limbic volume, such as midbrain BPnd, may be important for understanding the basis of drug craving, a key factor in the maintenance of substance-use disorders.

  10. 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

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

    Science.gov (United States)

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

    2006-03-18

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

  12. Misdiagnosed Pruritus; Formication due to Chronic Amphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Maryam Vahabzadeh

    2016-03-01

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

  13. Is brain gliosis a characteristic of chronic methamphetamine use in the human?

    Science.gov (United States)

    Tong, Junchao; Fitzmaurice, Paul; Furukawa, Yoshiaki; Schmunk, Gregory A; Wickham, Dennis J; Ang, Lee-Cyn; Sherwin, Allan; McCluskey, Tina; Boileau, Isabelle; Kish, Stephen J

    2014-07-01

    Animal data show that high doses of the stimulant drug methamphetamine can damage brain dopamine neurones; however, it is still uncertain whether methamphetamine, at any dose, is neurotoxic to human brain. Since gliosis is typically associated with brain damage and is observed in animal models of methamphetamine exposure, we measured protein levels (intact protein and fragments, if any) of markers of microgliosis (glucose transporter-5, human leukocyte antigens HLA-DRα [TAL.1B5] and HLA-DR/DQ/DPβ [CR3/43]) and astrogliosis (glial fibrillary acidic protein, vimentin, and heat shock protein-27) in homogenates of autopsied brain of chronic methamphetamine users (n=20) and matched controls (n=23). Intact protein levels of all markers were, as expected, elevated (+28%-1270%, Phuman recreational methamphetamine users who used the drug chronically and shortly before death. However, a logistically more difficult quantitative histopathological study is needed to confirm whether glial changes occur or do not occur in brain of human methamphetamine (and amphetamine) users.

  14. 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.

  15. 尿液中苯丙胺类毒品残留的MISPE-高效液相色谱法测定%Simultaneous determination of amphetamine homologues in urine by high-performance liquid chromatography with molecularly imprinted solid-phase extraction

    Institute of Scientific and Technical Information of China (English)

    陈琦君; 朱波; 金米聪

    2013-01-01

    Objective:To develop a method for the simultaneous deter mination of amphetamine homologues,such as methamphetamine (MA),amphetamine (AM),3,4-methylenedioxy-N-methamphetamine (MDMA),3,4-methylenedioxy-amphetamine (MDA) and 3-methoxy-4,5-methylenedioxy-amphetamine (MMDA) in urine by high-performance liquid chromatography with molecularly imprinted solid-phase extraction (MISPE).Methods:After the urine samples were mixed with 100 mmol/L ammonium acetate buffer (pH8.0) and centrifuged at 8000 rpm,the cleanup procedure was optimized on an activating MISPE cartridge with 1.0% acetate acid/acetonitrile (1/99,v/v) as elution.The separation was performed on an XBridge RP18 column by a mobile phase consisting of methanol-acetonitrile-100 mmol/L ammonium acetate solution for gradient elution.Detection was carried out by an ultraviolet detector at 215 nm.Results:Calibration curves of the five amphetamine homobgues were linear within the range of 0.05 mg/L ~ 15.0 mg/L with correlation coefficients more than 0.999.The limits of quantification (LOQs) were between 0.017 mg/L ~ 0.03 mg/L.The extraction recoveries were between 88.0% ~ 98.8%,and the RSDs were less than 5.0%.Conclusion:This developed method is simple,sensitive and accurate.It is suitable for the detection of the amphetamine homologue residues in biological specimens from drug users.%目的:建立快速、准确的尿液中甲基苯丙胺(MA)、苯丙胺(AM)、3,4-亚甲基二氧基甲基苯丙胺(MDMA)、3,4-亚甲基二氧基苯丙胺(MDA)、3-甲氧基-4,5-亚甲基二氧基苯丙胺(MMDA)残留的分子印迹固相萃取(MISPE)高效液相色谱测定方法.方法:尿液经与醋酸铵缓冲液(pH 8.0)混合后通过离心分离(8000 rpm),上清液采用预先活化的分子印迹固相萃取小柱净化,以1.0%醋酸/乙腈(1/99,v/v)溶液进行洗脱,在XBridge RP18色谱柱上,以甲醇-乙腈-100 mmol/L醋酸铵水溶液为流动相进行梯度洗脱,采用215 nm波长进行检测.结果:MA

  16. Boundary conditions of methamphetamine craving.

    Science.gov (United States)

    Lopez, Richard B; Onyemekwu, Chukwudi; Hart, Carl L; Ochsner, Kevin N; Kober, Hedy

    2015-12-01

    Methamphetamine use has increased significantly and become a global health concern. Craving is known to predict methamphetamine use and relapse following abstinence. Some have suggested that cravings are automatic, generalized, and uncontrollable, but experimental work addressing these claims is lacking. In 2 exploratory studies, we tested the boundary conditions of methamphetamine craving by asking: (a) is craving specific to users' preferred route of administration?, and (b) can craving be regulated by cognitive strategies? Two groups of methamphetamine users were recruited. In Study 1, participants were grouped by their preferred route of administration (intranasal vs. smoking), and rated their craving in response to photographs and movies depicting methamphetamine use (via the intranasal vs. smoking route). In Study 2, methamphetamine smokers implemented cognitive regulation strategies while viewing photographs depicting methamphetamine smoking. Strategies involved either focusing on the positive aspects of smoking methamphetamine or the negative consequences of doing so-the latter strategy based on treatment protocols for addiction. In Study 1, we found a significant interaction between group and route of administration, such that participants who preferred to smoke methamphetamine reported significantly stronger craving for smoking stimuli, whereas those who preferred the intranasal route reported stronger craving for intranasal stimuli. In Study 2, participants reported significantly lower craving when focusing on the negative consequences associated with methamphetamine use. Taken together, these findings suggest that strength of craving for methamphetamine is moderated by users' route of administration and can be reduced by cognitive strategies. This has important theoretical, methodological, and clinical implications.

  17. Effects of Methamphetamine on Pituitary Gonadal Axis and Spermatogenesis in Mature Male Rats

    Directory of Open Access Journals (Sweden)

    Malihe Heidari-Rarani

    2014-12-01

    Full Text Available Background: The use of methamphetamine has been significantly increased among youth in the last decade. Methamphetamine stimulates the central nervous system and affects on the body tissues and neurotransmitters like dopamine. In this study, the effect of methamphetamine as a medicine of amphetamine group is investigated on the pituitary-gonad axis and spermatogenesis. Materials and Methods: In this experimental study, 40 mature rats with 150±10 g weight are divided into in 4 groups including 10 rats in each group. Methamphetamine powder was weighted and it was solved in the normal saline to prepare a standard solution. Three experimental groups were injected in dosage 1, 3, 5 mg/kg using insulin syringe for 14 days, every day. Then, FSH, LH and testosterone concentrations were measured from the blood samples. The testis tissue was removed and after sectioning and staining by Hematoxylin-Eosin, was inspected by optical microscope for any changes. The average values of hormones and number of seminiferous cells were analyzed in SPSS-18 software using Duncan-test. Results: Experimental results showed that by increasing the concentration of methamphetamine, the serum level of LH and testosterone increase. While the FSH concentration decrease by increasing the level of methamphetamine. Also, investigation on the testis tissue showed that spermatogenesis has decreased on it in comparison to control group. This is because of methamphetamine effect on the gonads. Conclusion: The hormonal results and microscopic observations, it can conclude that using methamphetamine may cause destructive effects on pituitary-gonad axis and spermatogenesis and as a result, it may decrease fertility.

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

    Science.gov (United States)

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

    2009-12-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2000-03-01

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

  1. Rapid simultaneous determination of amphetamine,methamphetamine MDA and MDMA in urine using HS/SPME and GC/MS%顶空固相微萃取与气质联用快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA

    Institute of Scientific and Technical Information of China (English)

    李宏森; 黄克建; 林翠梧; 蒙念; 潘智文

    2007-01-01

    利用顶空固相微萃取(HS/SPME)结合气/质联用(GC/MS-SIM)技术同时快速检测尿液中苯丙胺、甲基苯丙胺、MDA和MDMA.80℃下采用100 μm聚二甲基硅氧烷萃取头萃取10 min,3-苯基-1-丙胺作内标,探讨了影响SPME萃取效果的萃取时间、盐浓度、酸碱条件等因素,优化了实验条件.结果:苯丙胺、甲基苯丙胺、MDA和MDMA在50~2000 ng/mL质量浓度范围内线性良好,相关系数(r2)分别为0.9985,0.9971,0.9928和0.9994,检测限(信噪比=3)0.09 ng/mL,0.02 ng/mL,1.71 ng/mL和0.15 ng/mL,定量限(信噪比=10)0.31 ng/mL,0.05 ng/mL,5.68 ng/mL,0.49 ng/mL.1 mL空白尿液加标250 ng和1 000 ng,回收率在82%~108%之间,相对标准偏差(RSD)<13%(n=5).建立的方法适用于尿液中苯丙胺、甲基苯丙胺、MDA和MDMA的同时快速检测.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-01-01

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

  3. Electrochemical Impedance Spectroscopic Sensing of Methamphetamine by a Specific Aptamer

    Directory of Open Access Journals (Sweden)

    Omid Mashinchian

    2012-05-01

    Full Text Available Introduction: Electrochemical impedance spectroscopy (EIS is a simple and highly sensitive technique that can be used for evaluation of the aptamer-target interaction even in a label-free approach. Methods: To pursue the effectiveness of EIS, in the current study, the folding properties of specific aptamer for methamphetamine (METH (i.e., aptaMETH were evaluated in the presence of METH and amphetamine (Amph. Folded and unfolded aptaMETH was mounted on the gold electrode surface and the electron charge transfer was measured by EIS. Results: The Ret of methamphetamine-aptaMETH was significantly increased in comparison with other folding conditions, indicating specific detection of METH by aptaMETH. Conclusion: Based on these findings, methamphetamine-aptaMETH on the gold electrode surface displayed the most interfacial electrode resistance and thus the most folding situation. This clearly indicates that the aptaMETH can profoundly and specifically pinpoint METH; as a result we suggest utilization of this methodology for fast and cost-effective identification of METH.

  4. Electrochemical Impedance Spectroscopic Sensing of Methamphetamine by a Specific Aptamer

    Science.gov (United States)

    Ebrahimi, Mohsen; Johari-Ahar, Mohammad; Hamzeiy, Hossein; Barar, Jaleh; Mashinchian, Omid; Omidi, Yadollah

    2012-01-01

    Introduction Electrochemical impedance spectroscopy (EIS) is a simple and highly sensitive technique that can be used for evaluation of the aptamer-target interaction even in a label-free approach. Methods To pursue the effectiveness of EIS, in the current study, the folding properties of specific aptamer for methamphetamine (METH) (i.e., aptaMETH) were evaluated in the presence of METH and amphetamine (Amph). Folded and unfolded aptaMETH was mounted on the gold electrode surface and the electron charge transfer was measured by EIS. Results The Ret of methamphetamine-aptaMETH was significantly increased in comparison with other folding conditions, indicating specific detection of METH by aptaMETH. Conclusion Based on these findings, methamphetamine-aptaMETH on the gold electrode surface displayed the most interfacial electrode resistance and thus the most folding situation. This clearly indicates that the aptaMETH can profoundly and specifically pinpoint METH; as a result we suggest utilization of this methodology for fast and cost-effective identification of METH. PMID:23678446

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

    Science.gov (United States)

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

    1999-10-01

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

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

    Science.gov (United States)

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

    1999-09-15

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

  7. Methamphetamine and paranoia: the methamphetamine experience questionnaire.

    Science.gov (United States)

    Leamon, Martin H; Flower, Keith; Salo, Ruth E; Nordahl, Thomas E; Kranzler, Henry R; Galloway, Gantt P

    2010-01-01

    Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. We administered the MEQ to 274 MA-dependent subjects. Of the total subjects, 45% (123) first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = .77, p paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the Brief Symptom Inventory (BSI) paranoid ideation scale (rho = .27, p paranoia on the MEQ and the BSI depression scale (rho = .14, p = .07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. (Am J Addict 2010;00:1-14).

  8. Methamphetamine and Paranoia: The Methamphetamine Experience Questionnaire

    Science.gov (United States)

    Leamon, Martin H.; Flower, Keith; Salo, Ruth E.; Nordahl, Thomas E.; Kranzler, Henry R.; Galloway, Gantt P.

    2011-01-01

    Paranoia in methamphetamine (MA) users is not well characterized or understood. To investigate this phenomenon, we created the Methamphetamine Experience Questionnaire (MEQ), and tested its reliability and validity in assessing MA-induced paranoia. METHODS: We administered the MEQ to 274 MA-dependent subjects. RESULTS: 45% (123) subjects first experienced paranoia with MA use; 55% did not. Obtaining or using a weapon while paranoid was common (37% and 11% of subjects with MA-induced paranoia, respectively). Test-retest and inter-rater reliability for MA-induced paranoia showed substantial agreement (kappa = 0.77, p < 0.05 and kappa = 0.80, p < 0.05, respectively). First episodes of paranoia occurred more often with intravenous use of MA, and subsequent episodes at higher doses. There was modest correlation between paranoia on the MEQ and the BSI paranoid ideation scale (rho = 0.27, p < 0.05). As expected, there was a poor correlation between paranoia on the MEQ and the BSI depression scale (rho = 0.14, p = 0.07). The MEQ provides useful information on drug use variables that contribute to paranoia commonly associated with MA use. PMID:20163388

  9. Rapid simultaneous determination of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by GC-MS.

    Science.gov (United States)

    Saito, Takeshi; Mase, Hiroyasu; Takeichi, Sanae; Inokuchi, Sadaki

    2007-01-04

    This paper presents a simple and sensitive chromatographic procedure for the simultaneous determination and quantification of ephedrines, amphetamines, cocaine, cocaine metabolites, and opiates in human urine by gas chromatography-mass spectrometry. This method involves enzyme hydrolysis in the presence of a deuterated internal standard, liquid-liquid extraction, and derivatization with pentafluoropropionic anhydride and pentafluoropropanol. The recovery of each compound averaged at 65.8% or more. The limits of detection determined for each compound by using a 2-mL sample volume ranged from 5 to 50 ng/mL. The calibration curves were linear to 100 ng/mL for all compounds when determined using methamphetamine-d4 and MDMA-d5 as internal standards. This method was successfully applied for the analysis of urine samples suspected to contain intoxicants such as methamphetamine and heroin.

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

    Science.gov (United States)

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

    2006-01-01

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

  11. Methamphetamine Psychosis: Epidemiology and Management

    Science.gov (United States)

    Glasner-Edwards, Suzette; Mooney, Larissa J.

    2016-01-01

    Psychotic symptoms and syndromes are frequently experienced among individuals who use methamphetamine, with recent estimates of up to approximately 40% of users affected. Though transient in a large proportion of users, acute symptoms can include agitation, violence, and delusions, and may require management in an inpatient psychiatric or other crisis intervention setting. In a subset of individuals, psychosis can recur and persist and may be difficult to distinguish from a primary psychotic disorder such as schizophrenia. Differential diagnosis of primary versus substance-induced psychotic disorders among methamphetamine users is challenging; nevertheless, with careful assessment of the temporal relationship of symptoms to methamphetamine use, aided by state-of-the art psychodiagnostic assessment instruments and use of objective indicators of recent substance use (i.e., urine toxicology assays), coupled with collateral clinical data gathered from the family or others close to the individual, diagnostic accuracy can be optimized and the individual can be appropriately matched to a plan of treatment. The pharmacological treatment of acute methamphetamine-induced psychosis may include the use of antipsychotic medications as well as benzodiazepines, although symptoms may resolve without pharmacological treatment if the user is able to achieve a period of abstinence from methamphetamine. Importantly, psychosocial treatment for methamphetamine dependence has a strong evidence base and is the optimal first-line treatment approach to reducing rates of psychosis among individuals who use methamphetamines. Prevention of methamphetamine relapse is the most direct means of preventing recurrence of psychotic symptoms and syndromes. Long-term management of individuals who present with recurrent and persistent psychosis, even in the absence of methamphetamine use, may include both behavioral treatment to prevent resumption of methamphetamine use and pharmacological treatment

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

    Science.gov (United States)

    DePace, A; Verebey, K; elSohly, M

    1990-11-01

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

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

    Science.gov (United States)

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

    2004-07-16

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

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

    Science.gov (United States)

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

    2005-06-01

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

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Science.gov (United States)

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

    2016-05-20

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2003-03-01

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

  19. T-Mobile MDA Pro

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    T-Mobile MDA Pro是T-Mobile推出的Windows Mobile 5.0智能手机,采用520MHz PXA270 CPU,支持GSM 900/1800/1900MHz GPRS CLASS10A,支持WCDMA 2100MHz(3G),可旋转屏幕分辨率为640×480像素。

  20. Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid phase microextraction coupled to high performance liquid chromatography and analysis of amphetamines in urine samples.

    Science.gov (United States)

    Fan, Yi; Feng, Yu-Qi; Zhang, Jian-Tao; Da, Shi-Lu; Zhang, Min

    2005-05-13

    In-tube solid-phase microextraction (SPME) based on a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column was investigated for the extraction of amphetamine, methamphetamine and their methylenedioxy derivatives. The monolithic capillary column showed high extraction efficiency towards target analytes, which could be attributed to its larger loading amount of extraction phase than conventional open-tubular extraction capillaries and the convective mass transfer procedure provided by its monolithic structure. The extraction mechanism was studied, and the results indicated that the extraction process of the target analytes was involved with hydrophobic interaction and ion-exchange interaction. The polymer monolith in-tube SPME-HPLC system with UV detection was successfully applied to the determination of amphetamine, methamphetamine and their methylenedioxy derivatives in urine samples, yielding the detection limits of 1.4 - 4.0 ng/mL. Excellent method reproducibility (RSD urine samples.

  1. Recent Advances in Methamphetamine Neurotoxicity Mechanisms and Its Molecular Pathophysiology

    Directory of Open Access Journals (Sweden)

    Shaobin Yu

    2015-01-01

    Full Text Available Methamphetamine (METH is a sympathomimetic amine that belongs to phenethylamine and amphetamine class of psychoactive drugs, which are widely abused for their stimulant, euphoric, empathogenic, and hallucinogenic properties. Many of these effects result from acute increases in dopamine and serotonin neurotransmission. Subsequent to these acute effects, METH produces persistent damage to dopamine and serotonin release in nerve terminals, gliosis, and apoptosis. This review summarized the numerous interdependent mechanisms including excessive dopamine, ubiquitin-proteasome system dysfunction, protein nitration, endoplasmic reticulum stress, p53 expression, inflammatory molecular, D3 receptor, microtubule deacetylation, and HIV-1 Tat protein that have been demonstrated to contribute to this damage. In addition, the feasible therapeutic strategies according to recent studies were also summarized ranging from drug and protein to gene level.

  2. 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

  3. High-throughput analysis of amphetamines in blood and urine with online solid-phase extraction-liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fernández, María del Mar Ramírez; Wille, Sarah M R; Samyn, Nele; Wood, Michelle; López-Rivadulla, Manuel; De Boeck, Gert

    2009-01-01

    An automated online solid-phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS-MS) method for the analysis of amphetamines in blood and urine was developed and validated. Chromatographic separation was achieved on a Nucleodur Sphinx RP column with an LC gradient (a mixture of 10 mM ammonium formate buffer and acetonitrile), ensuring the elution of amphetamine, methamphetamine, MDMA, MDA, MDEA, PMA, and ephedrine within 11 min. The method was fully validated, according to international guidelines, using only 100 and 50 microL of blood and urine, respectively. The method showed an excellent intra- and interassay precision (relative standard deviation 0.99, 2.5-400 microg/L for blood and 25-1000 microg/L for urine). Limits of quantification were determined to be 2.5 and 25 microg/L for blood and urine, respectively. Limits of detection ranged from 0.05 to 0.5 microg/L for blood and 0.25 to 2.5 microg/L for urine, depending on the compound. Furthermore, the analytes and the processed samples were demonstrated to be stable (in the autosampler for at least 72 h and after three freeze/thaw cycles), and no disturbing matrix effects were observed for all compounds. Moreover, no carryover was observed after the analysis of high concentration samples (15,000 microg/L). The method was subsequently applied to authentic blood and urine samples obtained from forensic cases, which covered a broad range of concentrations. The validation results and actual sample analyses demonstrated that this method is rugged, precise, accurate, and well-suited for routine analysis as more than 72 samples are analyzed non-stop in 24 h with minimum sample handling. The combination of the high-throughput online SPE and the well-known sensitivity and selectivity assured by MS-MS resulted in the elimination of the bottleneck associated with the sample preparation requirements and provided increased sensitivity, accuracy, and precision.

  4. The use of cyclohexanone as a "derivatizing" reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine.

    Science.gov (United States)

    El-Haj, B M; Al-Amri, A M; Hassan, M H; Ali, H S; Bin Khadem, R K

    2003-07-29

    A GC-MS method has been developed for the detection of amphetamine, methamphetamine, and the ephedrines, in seizures and the urine, based on on-GC condensation (derivatization) with cyclohexanone. The method is simple: the dried seizure material or the urine extract was mixed with cyclohexanone and injected into the GC-MS. The method was found to be superior to the methods based on acyl and trimethylsilyl (TMS) derivatization. Unlike for the acyl and TMS derivatives, the molecular and fragment ions of the cyclohexanone condensation products (cyclohexanone derivatives) were of substantial abundance, a useful property in unambiguous compound characterization. Furthermore, the high stability of the "derivatizing" reagent, cyclohexanone, compared with acyl and TMS derivatizing reagents, is a useful property in method development. The present method has proved selective and, tentatively, sensitive enough in the following areas (where methods based on acyl and TMS derivatization, as tested in this laboratory, have failed): (a) detection of amphetamine as a metabolite of methamphetamine; (b) detection of norpseudoephedrine as a metabolite of pseudoephedrine; (c) detection of amphetamine as an impurity of methamphetamine; (d) detection of cathine (norephedrine) as a constituent of Khat leaves; and (e) differentiation of Khat use from phenylpropanolamine use.

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

    Science.gov (United States)

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

    2015-03-01

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

  6. Applicability of chemically modified capillaries in chiral capillary electrophoresis for methamphetamine profiling.

    Science.gov (United States)

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

    2013-03-10

    We examined the applicability of chemically modified capillaries on the chiral capillary electrophoresis of essential compounds for methamphetamine (MA) profiling (MA, amphetamine, ephedrine, pseudoephedrine, norephedrine, and norpseudoephedrine) using highly sulfated γ-cyclodextrin as a chiral selector. Four types of chemically modified capillaries, namely, FunCap-CE/Type D (possessing diol groups), Type A (amino groups), Type C (carboxyl groups), and Type S (sulfate groups), were evaluated. Repeatability, speed, and good chiral resolution sufficient for routine MA profiling were achieved with the Type S capillary.

  7. Prenatal Methamphetamine Exposure Linked with Problems

    Science.gov (United States)

    ... IDEAL reports linked prenatal methamphetamine exposure to reduced neonatal size (“ Methamphetamine Restricts Fetal Growth, Increases Lethargy in ... AIDS Medical Consequences Mental Health Military and Veterans Pain Prevention Research Training Treatment Research Trends and Statistics ...

  8. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    Science.gov (United States)

    ... after the methamphetamine exposure, and obtained magnetic resonance images (MRI) of the brain before and after the exposure. Figure 1. Reversal Trial Studies the Impact of Methamphetamine on Monkeys’ Mental Flexibility The trial evaluates an animal’s mental ...

  9. Irreversible brain damage caused by methamphetamine

    Directory of Open Access Journals (Sweden)

    Sebastian Moeller

    2016-03-01

    Full Text Available Methamphetamine is an addictive scene substance usage of which is increasing rapidly. While methamphetamine often causes neuropsychiatric symptoms like anxiety, psychosis and hallucinations, reports of structural ongoing cerebral alterations are rare. We here report a case of this kind of damage caused through methamphetamine use.

  10. The Comparison of Attentional Bias and Difficulty of Emotional States Regulation and Their Correlation with Craving Severity in Drug Abuser Methamphetamines and Crack

    OpenAIRE

    Raheleh Haghiaght; Nezamaddin Ghasemi; Mehdi Rabiei; Asghar Zerehposh; Ahmadreza Kiani

    2014-01-01

    Background: Today, within creased substance, type of substance used has changed. Therefore, drug abuse in population of crack to the stimulant drugs (amphetamine) particularly crystal is expanding and increasing. Therefore, the purpose of the present study was the comparison of attentional bias and difficulty of emotional states regulation and their correlation with craving severity in drug abuser methamphetamines and crack. Materials and Methods: Type of research was descriptive analytic...

  11. 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

    laboratories of toxicology of the development countries as Brazil. It was chosen for development and validation a gas chromatography method with flame ionization detection. The analytic validation results for MDMA, MDA and MDEA were linearity range of 1.0 to 500.0 µg/mL, intra and interassay coefficient of variation lower than 9.5% and quantification limit of 1.0 µg/mL. The detection limits were 0.7 µg/mL, 0.8 µg/mL and 0.6 µg/mL respectively to MDMA, MDA and MDEA. The method showed a good seletivity as the epinephrine, cocaine, amphetamine, methamphetamine, acethyl salicilic acid, diethyl barbituric acid, p-aminobenzoyl diethyl barbituric, paracetamol and caffeine presences did not interfere with the measurement of the three analytes.

  12. Meth math: modeling temperature responses to methamphetamine.

    Science.gov (United States)

    Molkov, Yaroslav I; Zaretskaia, Maria V; Zaretsky, Dmitry V

    2014-04-15

    Methamphetamine (Meth) can evoke extreme hyperthermia, which correlates with neurotoxicity and death in laboratory animals and humans. The objective of this study was to uncover the mechanisms of a complex dose dependence of temperature responses to Meth by mathematical modeling of the neuronal circuitry. On the basis of previous studies, we composed an artificial neural network with the core comprising three sequentially connected nodes: excitatory, medullary, and sympathetic preganglionic neuronal (SPN). Meth directly stimulated the excitatory node, an inhibitory drive targeted the medullary node, and, in high doses, an additional excitatory drive affected the SPN node. All model parameters (weights of connections, sensitivities, and time constants) were subject to fitting experimental time series of temperature responses to 1, 3, 5, and 10 mg/kg Meth. Modeling suggested that the temperature response to the lowest dose of Meth, which caused an immediate and short hyperthermia, involves neuronal excitation at a supramedullary level. The delay in response after the intermediate doses of Meth is a result of neuronal inhibition at the medullary level. Finally, the rapid and robust increase in body temperature induced by the highest dose of Meth involves activation of high-dose excitatory drive. The impairment in the inhibitory mechanism can provoke a life-threatening temperature rise and makes it a plausible cause of fatal hyperthermia in Meth users. We expect that studying putative neuronal sites of Meth action and the neuromediators involved in a detailed model of this system may lead to more effective strategies for prevention and treatment of hyperthermia induced by amphetamine-like stimulants.

  13. 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.

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

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    Gouzoulis-Mayfrank, Euphrosyne; Daumann, Joerg

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-08-01

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

  17. Determination of amphetamines in urine by hollow fiber-based liquid-phase microextraction and chromatography-mass spectrometry%中空纤维膜液相微萃取-气相色谱/质谱法检测尿液中的苯丙胺类兴奋剂

    Institute of Scientific and Technical Information of China (English)

    张文文; 孟品佳; 孟梁; 王丹

    2013-01-01

    建立了尿液中痕量苯丙胺类毒品的中空纤维膜液相微萃取-气相色谱/质谱检测方法.采用中空纤维膜液相微萃取技术萃取尿液中4种苯丙胺类毒品,研究萃取剂类型、体积、溶液pH、萃取时间和温度等对萃取效果的影响.尿液中4种苯丙胺类毒品的最佳萃取条件为:样品溶液pH 13,甲苯为萃取剂,搅拌速度500 r/min,30 ℃条件下萃取15 min;此条件下苯丙胺(AM)、甲基苯丙胺(MAM)、3,4-亚甲二氧基苯丙胺(MDA)、3,4-亚甲二氧基甲基苯丙胺(MDMA)的检出限(S/N=3)分别为1.0,0.75,1.0,0.64 ng/mL,相对标准偏差分别为6.62%,3.98%,4.57%,2.35%,富集倍数分别为155,170,132,218倍.本方法可用于尿液中痕量苯丙胺类毒品的分析测定.%Objective A novel method was developed to determine the trace amounts of amphetamine-type stimulants in urine by GC-MS coupled with hollow fiber membrane solvent microextraction. Methods Hollow fiber membrane liquid phase microextraction technology was adopted to extract amphetamines in urine after optimization of extraction conditions, such as solvent, volume, pH, stirring speed, time and temperature. Results Optimization of the extraction for amphetamines in urine was; toluene being used as extraction solvent, the target analytes in urine were extracted under pH 13 with temperature at 30 ℃ , stirring speed at 500 r/min, for 15 min. Under the optimized conditions, the LODs of amphetamine, methamphetamine, MDA, MDMA were 1. 0, 0. 75 , 1. 0 and 0. 64 ng/mL; the RSDs were 6. 62% , 3. 98% , 4. 57% , 2. 35% ; and the enrichment factors were 155, 170, 132, 218, respectively. Conclusion The results demonstrated that the method was feasible for the determination of the trace amounts of amphetamine-type stimulants in urine.

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

    Science.gov (United States)

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

    2006-12-22

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

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

    Science.gov (United States)

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

    2004-10-15

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

  20. Towards an MDA-based development methodology

    NARCIS (Netherlands)

    Gavras, Anastasius; Belaunde, Mariano; Ferreira Pires, Luis; Almeida, João Paolo A.; Oquendo, Flavio; Warboys, Brian C.; Morrison, Ron

    2004-01-01

    This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

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

  3. Amphetamine Abuse Related Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Archana Sinha

    2016-01-01

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

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

    Science.gov (United States)

    Marais, Adriaan A S; Laurens, Johannes B

    2009-01-10

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

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

    Science.gov (United States)

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

    2014-09-01

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

  6. Methamphetamine Use and Oral Health

    Science.gov (United States)

    FOR THE DENTAL PATIENT ... Methamphetamine use and oral health M ethamphetamine is an inexpensive, easy-to-make illicit drug. It is known by several street names: “meth,” “speed,” “ice,” “chalk,” “crank,” “fire,” “ ...

  7. 21 CFR 862.3100 - Amphetamine test system.

    Science.gov (United States)

    2010-04-01

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

  8. Substance abuse and HIV: considerations with regard to methamphetamines and other recreational drugs for nursing practice and research.

    Science.gov (United States)

    Gorman, E M; Carroll, R T

    2000-01-01

    Substance use continues to be closely associated with both HIV infection and treatment considerations in all at-risk populations. Among those groups heretofore not well characterized epidemiologically or clinically are those dual-risk men who have sex with other men (MSM) and use and/or inject drugs. Of particular current concern with regard to drug-using MSM is the growth in popularity of a group of recreational or so-called party drugs associated with specific social and sexual environments and networks. Chief among these drugs are hallucinogens, such as MDMA, ketamine, and GHB, and stimulants, such as cocaine, amphetamines, and methamphetamine. Increased methamphetamine use by MSM is particularly alarming because of its reported associations with high-risk injecting and sexual behaviors. Preliminary data are reported from an ethnographic exploration of MSM methamphetamine users in the Pacific Northwest of the United States. Case studies drawn from the data illustrate the complex and variable patterns of methamphetamine use among MSM. Finally, implications for nursing are discussed, and "upstream nursing" is suggested as a means of patient advocacy for HIV nurses working with substance-using populations.

  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. Methamphetamine intoxication in a dog: case report

    OpenAIRE

    Pei, Zengyang; Zhang, Xu

    2014-01-01

    Background Methamphetamine abuse has undergone a dramatic worldwide increase, and represents a significant and global issue for public health. Incidents of methamphetamine intoxication and death in humans are relatively commonplace. Because of its increasing illicit availability, together with legitimate use in human medicine, accidental or intentional exposure to methamphetamine in dogs is becoming a more likely scenario. Case presentation A 3-year-old, 3.7 kg intact female Miniature Poodle ...

  11. Methamphetamine/Dextroamphetamine and Pregnancy

    Science.gov (United States)

    ... and are found in the baby’s body and urine. We do not know if this causes the baby to have problems, but when taken as directed by a health care provider, some evidence shows amphetamines do not affect nursing infants. A small study ...

  12. Cross-reactivities of various phenethylamine-type designer drugs to immunoassays for amphetamines, with special attention to the evaluation of the one-step urine drug test Instant-View™, and the Emit® assays for use in drug enforcement.

    Science.gov (United States)

    Nakanishi, Keiko; Miki, Akihiro; Zaitsu, Kei; Kamata, Hiroe; Shima, Noriaki; Kamata, Tooru; Katagi, Munehiro; Tatsuno, Michiaki; Tsuchihashi, Hitoshi; Suzuki, Koichi

    2012-04-10

    Cross-reactivities of 76 kinds of phenethylamine-type designer drugs and related compounds to the urine drug tests Instant-View ™ (IV) (the Methamphetamine (MA) test, the Amphetamine 300 test, and the MDMA test) have been investigated. An on-site urine test kit consisting of these three IV tests has been evaluated for the on-site screening of MA users, and the kit has been found to have satisfactory specificity for drug enforcement purposes by separately detecting both MA and its metabolite amphetamine. The cross-reactivity profiles of Emit(®) II Plus Amphetamines Assay, Emit(®) II Plus Ecstasy assay, and Emit(®) d.a.u.(®) Amphetamine Class assay have also been investigated and discussed.

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

    Science.gov (United States)

    Jakobsson, Gerd; Kronstrand, Robert

    2014-06-01

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

  14. Risk for Neurobehavioral Disinhibition in Prenatal Methamphetamine-Exposed Young Children with Positive Hair Toxicology Results

    Science.gov (United States)

    Himes, Sarah K.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Smith, Lynne M.; Arria, Amelia M.; Grotta, Sheri A. Della; Dansereau, Lynne M.; Abar, Beau; Neal, Charles R.; Lester, Barry M.; Huestis, Marilyn A.

    2014-01-01

    Background The objective was to evaluate effects of prenatal methamphetamine exposure (PME) and postnatal drug exposures identified by child hair analysis on neurobehavioral disinhibition at 6.5 years of age. Methods Mother-infant pairs were enrolled in the Infant Development, Environment, and Lifestyle (IDEAL) Study in Los Angeles, Honolulu, Tulsa and Des Moines. PME was determined by maternal self-report and/or positive meconium results. At the 6.5-year follow-up visit, hair was collected and analyzed for methamphetamine, tobacco, cocaine, and cannabinoid markers. Child behavioral and executive function test scores were aggregated to evaluate child neurobehavioral disinhibition. Hierarchical linear regression models assessed the impact of PME, postnatal substances, and combined PME with postnatal drug exposures on the child’s neurobehavioral disinhibition aggregate score. Past year caregiver substance use was compared to child hair results. Results A total of 264 children were evaluated. Significantly more PME children (n=133) had hair positive for methamphetamine/amphetamine (27.1% versus 8.4%) and nicotine/cotinine (38.3% versus 25.2%) than children without PME (n=131). Overall, no significant differences in analyte hair concentrations were noted between groups. Significant differences in behavioral and executive function were observed between children with and without PME. No independent effects of postnatal methamphetamine or tobacco exposure, identified by positive hair test, were noted and no additional neurobehavioral disinhibition was observed in PME children with postnatal drug exposures, as compared to PME children without postnatal exposure. Conclusions Child hair testing offered a non-invasive means to evaluate postnatal environmental drug exposure, although no effects from postnatal drug exposure alone were seen. PME, alone and in combination with postnatal drug exposures, was associated with behavioral and executive function deficits at 6.5 years

  15. A high-throughput method based on microwave-assisted extraction and liquid chromatography-tandem mass spectrometry for simultaneous analysis of amphetamines, ketamine, opiates, and their metabolites in hair.

    Science.gov (United States)

    Chang, Yuan-Jhe; Chao, Mu-Rong; Chen, Su-Chin; Chen, Chih-Hong; Chang, Yan-Zin

    2014-04-01

    A total sample-preparation and analysis time of 50 min is required for the high-throughput method of hair analysis proposed in this paper. The method is applicable to analysis of drugs commonly used in Asia, and their metabolites--methamphetamine (MA), amphetamine (AMP), methylenedioxymethamphetamine (MDMA), methylenedioxyamphetamine (MDA), ketamine (K), norketamine (NK), dehydronorketamine (DHNK), 6-acetylmorphine (6-AM), morphine (MOR), and codeine (COD). Cut and weighed hair (10 mg) was incubated for 3 min with methanol-trifluoroacetic acid (TFA) during microwave-assisted extraction (MAE) at 700 W. The incubation solution was evaporated, the residue was reconstituted in deionized water-methanol, 99:1 (v/v), and 20 μL was injected on to a core-shell column (50 × 4.6 mm, 2.6 μm particle size) for liquid chromatographic-tandem mass spectrometric (LC-MS-MS) analysis. Gradient elution separation was performed in 8 min at a flow rate of 1 mL min(-1). No signal interfering with any of the analytes was found in fourteen blank hair samples from different sources. The limits of detection and quantification were 0.5 pg mg(-1) and 2.0 pg mg(-1), respectively, for MA, AMP, MDMA, MDA, K, NK, and DHNK, and 2.0 pg mg(-1) and 5.0 pg mg(-1), respectively, for 6-AM, MOR and COD. The linear range was between the LOQ and 1000 pg mg(-1), and the correlation coefficients were all greater than 0.999. Investigation of matrix effects revealed that all the analytes were suppressed by less than 20% and the standard deviation (SD) was always less than 7%. Recovery was always greater than 90% and the SD for each compound was less than 6%. Precision and accuracy for each analyte were within 15%. Eight authentic hair specimens from known drug abusers were successfully analyzed. Compared with traditional overnight incubation methods, the rapid 3-min extraction time achieved similar or greater extraction yields. Sample preparation by MAE was a reliable procedure for extraction of the

  16. [Determination of amphetamines in human urine using microwave extraction-gas chromatography].

    Science.gov (United States)

    Wang, Jifen; Sun, Hongfeng; Ye, Nengsheng; Gu, Xuexin; Li, Wenjun; Li, Ying

    2008-03-01

    A method has been developed for the determination of methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in human urine using microwave extraction-gas chromatography(GC). To improve the extraction efficiency, experimental parameters of the extraction, including extraction solvent and its amount, pH value of the urine sample, extraction time and temperature were investigated. The optimal conditions were as follows: the pH value of urine sample at pH 12, cyclohexane as extraction solvent, extraction at 40 degrees C for 10 min. The average recoveries of MA, MDA and MDMA with this extraction method were 92.25%, 85.94% and 91.50%, the relative standard deviations were 5.5%, 5.5% and 6.1%(n = 5), and the limits of detection were 10, 20 and 20 ng/mL, respectively. Using this method, MA, MDA and MDMA need not be derivatized and can be separated from the matrix. The results indicate that the developed method is rapid, accurate and sensitive, and can be used for the simultaneous determination of MA, MDA and MDMA in urine samples.

  17. Evaluation of the 20% D-methamphetamine requirement for determining illicit use of methamphetamine in urine.

    Science.gov (United States)

    Esposito, Francis M; Crumpton, Susan; Mitchell, John; Flegel, Ronald R

    2012-07-01

    In urine drug testing, enantiomer analysis is used to determine whether a positive methamphetamine result could be due to use of an over-the-counter (OTC) nasal inhaler containing L-methamphetamine. D-methamphetamine at more than 20% of the total is considered indicative of a source other than an OTC product. This interpretation is based on a 1991 Department of Health and Human Services (HHS) Technical Advisory. We performed studies to verify the methamphetamine enantiomer content of current OTC nasal inhalers and to evaluate current laboratory testing capabilities. This study demonstrated that OTC inhalers contain less than 1% D-methamphetamine. A proficiency testing (PT) set for HHS-certified laboratories performing methamphetamine enantiomer testing found D-methamphetamine percentages that were consistently 1 to 3% higher than theoretical due to optical impurity of the derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC). The PT results also demonstrate that laboratories can accurately determine 20% D-methamphetamine in samples with total methamphetamine concentrations down to 250 ng/mL. Based on these studies, the guideline of >20% D-methamphetamine is appropriate for interpreting results obtained using current laboratory methods.

  18. 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.

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

    Science.gov (United States)

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

    2014-03-01

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

  20. 甲基苯丙胺依赖与中脑边缘多巴胺神经系统相关研究%Methamphetamine Dependence and Mesocorticolimbic Dopaminergic System

    Institute of Scientific and Technical Information of China (English)

    陈群; 周文华

    2012-01-01

    以甲基苯丙胺为代表的苯胺类中枢兴奋剂滥用问题日益突出,文章对甲基苯丙胺依赖的作用途径和机制进行了概述,包括中脑边缘系统多巴胺神经通路、多巴胺受体、多巴胺转运体及其他神经递质,最后提出了当前甲基苯丙胺成瘾治疗研究的主要方向.%As one of the amphetamine type stimulants, methamphetamine has been abused widely in China. The methamphetamine dependence is related to the mesocorticolimbic dopaminergic system. This paper describes the mechanisms underlying methamphetamine dependence on the dopamine release, dopamine receptors and dopamine transporter.

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

    Science.gov (United States)

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

    2013-12-01

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

  2. 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 ...

  3. Raman Optical Activity and Raman Spectra of Amphetamine Species

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  4. D-amphetamine and delinquency: hyperkinesis persisting?

    Science.gov (United States)

    Maletzky, B M

    1974-12-01

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

  5. School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5 Year Follow-Up From The Infant Development, Environment, and Lifestyle (IDEAL) Study

    Science.gov (United States)

    Eze, Nwando; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Arria, Amelia; Huestis, Marilyn A.; Della Grotta, Sheri A; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2016-01-01

    Objective To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years, and the extent to which early adversity mediated this relationship. Study design The multicenter, longitudinal IDEAL study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n= 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5 year follow-up, 290 children with complete Child Behavior Checklist (CBCL) data and an early adversity index score were available for analysis (n=146 exposed). Results PME was significantly associated with an increased early adversity index score (P<0.001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P<0.05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant. Conclusion Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems. PMID:26781836

  6. On MDA - SOA based Intercloud Interoperability framework

    Directory of Open Access Journals (Sweden)

    Tahereh Nodehi

    2013-01-01

    Full Text Available Cloud computing has been one of the latest technologies which assures reliable delivery of on - demand computing services over the Internet. Cloud service providers have established geographically distributed data centers and computing resources, which are available online as service. The clouds operated by different service providers working together in collaboration can open up lots more spaces for innovative scenarios with huge amount of resources provisioning on demand. However, current cloud systems do not support intercloud interoperability. This paper is thus motivated to address Intercloud Interoperabilityby analyzing different methodologies that have been applied to resolve various scenarios of interoperability. Model Driven Architecture (MDA and Service Oriented Architecture (SOA method have been used to address interoperability in various scenarios, which also opens up spaces to address intercloud interoperability by making use of these well accepted methodologies. The focus of this document is to show Intercloud Interoperability can be supported through a Model Driven approach and Service Oriented systems. Moreover, the current state of the art in Intercloud, concept and benefits of MDA and SOA are discussed in the paper. At the same time this paper also proposes a generic architecture for MDA - SOA based framework, which can be useful for developing applications which will require intercloud interoperability. The paper justi fies the usability of the framework by a use - case scenario for dynamic workload migration among heterogeneous clouds.

  7. Stress-Induced Enzyme Compounds Methamphetamine Neurotoxicity

    Science.gov (United States)

    ... Methamphetamine Neurotoxicity Email Facebook Twitter January 29, 2014 Ketoprofen, an anti-inflammatory agent commonly prescribed to treat ... of the University of Toledo, Ohio, gave animals ketoprofen to investigate the role of inflammation in producing ...

  8. Methamphetamine psychosis, the efficacy of atypical antipsychotics

    Directory of Open Access Journals (Sweden)

    Amir Rezaei Ardani

    2014-12-01

    Full Text Available Worldwide growing methamphetamine abuse is one of the most serious health problems with several different consequences for victims, especially in developing countries. Chronic methamphetamine abuse is associated with several psychiatric problems in all countries which are faced to epidemic methamphetamine abuse. Methamphetamine-induced psychosis is a major medical challenge for clinical practitioner from both diagnostic and therapeutic viewpoints. Stimulant psychosis commonly occurs in people who abuse stimulants, but it also occurs in some patients taking therapeutic doses of stimulant drugs under medical supervision. The main characteristic of meth psychosis is the presence of prominent hallucinations and delusions. Other drugs, such as cocaine and marijuana, can trigger the onset of psychosis in someone who is already at increased risk because they have “vulnerability”.The current literature review attends to explain several aspects of MIP epidemiologically and clinically. Investigators proposed pharmacologically treatment based on recently published data.

  9. MDMA, methamphetamine, and CYP2D6 pharmacogenetics: what is clinically relevant?

    Directory of Open Access Journals (Sweden)

    Rafael eDe La Torre

    2012-11-01

    Full Text Available In vitro human studies show that the metabolism of most amphetamine-like psychostimulants is regulated by the polymorphic cytochrome P450 isozyme CYP2D6. Two compounds, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA, were selected as archetypes to discuss the translation and clinical significance of in vitro to in vivo findings. Both compounds were chosen based on their differential interaction with CYP2D6 and their high abuse prevalence in society. Methamphetamine behaves as both a weak substrate and competitive inhibitor of CYP2D6, while MDMA acts as a high affinity substrate and potent mechanism-based inhibitor (MBI of the enzyme. The MBI behavior of MDMA on CYP2D6 implies that subjects, irrespective of their genotype/phenotype, are phenocopied to the poor metabolizer phenotype. The fraction of metabolic clearance regulated by CYP2D6 for both drugs is substantially lower than expected from in vitro studies. Other isoenzymes of cytochrome P450 and a relevant contribution of renal excretion play a part in their clearance. These facts tune down the potential contribution of CYP2D6 polymorphism in the clinical outcomes of both substances. Globally, the clinical relevance of CYP2D6 polymorphism is lower than that predicted by in vitro studies.

  10. Effects of cocaine, methamphetamine and modafinil challenge on sleep rebound after paradoxical sleep deprivation in rats

    Directory of Open Access Journals (Sweden)

    R.C.S Martins

    2008-01-01

    Full Text Available Sleep loss is both common and critically relevant to our society and might lead to the abuse of psychostimulants such as amphetamines, cocaine and modafinil. Since psychoactive substance abuse often occurs within a scenario of sleep deficit, the purpose of this investigation was to compare the sleep patterns of rats challenged with cocaine (7 mg/kg, ip, methamphetamine (7 mg/kg, ip, or modafinil (100 mg/kg, ip subsequent to paradoxical sleep deprivation (PSD for 96 h. Our results show that, immediately after 96 h of PSD, rats (10 per group that were injected with a psychostimulant presented lower percentages of paradoxical sleep compared to those injected with saline (P < 0.01. Regarding slow wave sleep (SWS, rats injected with psychostimulants after PSD presented a late rebound (on the second night subsequent to the injection in the percentage of this phase of sleep when compared to PSD rats injected with saline (P < 0.05. In addition, the current study has produced evidence of the characteristic effect of each drug on sleep architecture. Home cage control rats injected with modafinil and methamphetamine showed a reduction in SWS compared with the saline group. Methamphetamine affected sleep patterns most, since it significantly reduced paradoxical sleep, SWS and sleep efficiency before and after PSD compared to control (P < 0.05. Cocaine was the psychostimulant causing the least changes in sleep pattern in relation to those observed after saline injection. Therefore, our results suggest that abuse of these psychostimulants in a PSD paradigm aggravates their impact on sleep patterns.

  11. Prenatal methamphetamine exposure and neonatal neurobehavioral outcome in the USA and New Zealand

    Science.gov (United States)

    LaGasse, Linda L.; Wouldes, Trecia; Newman, Elana; Smith, Lynne M.; Shah, Rizwan Z.; Derauf, Chris; Huestis, Marilyn A.; Arria, Amelia M.; Grotta, Sheri Della; Wilcox, Tara; Lester, Barry M.

    2010-01-01

    Background Methamphetamine (MA) use among pregnant women is a world-wide problem, but little is known of its impact on exposed infants. Design The prospective, controlled longitudinal Infant Development, Environment and Lifestyle (IDEAL) study of prenatal MA exposure from birth to 36 months was conducted in the US and NZ. The US cohort has 183 exposed and 196 comparison infants; the NZ cohort has 85 exposed and 95 comparison infants. Exposure was determined by self-report and meconium assay with alcohol, marijuana, and tobacco exposures present in both groups. The NICU Neurobehavior Scale (NNNS) was administered within 5 days of life. NNNS summary scores were analyzed for exposure including heavy exposure and frequency of use by trimester and dose-response relationship with the amphetamine analyte. Results MA Exposure was associated with poorer quality of movement, more total stress/abstinence, physiological stress, and CNS stress with more nonoptimal reflexes in NZ but not in the USA. Heavy MA exposure was associated with lower arousal and excitability. First trimester MA use predicted more stress and third trimester use more lethargy and hypotonicity. Dose-response effects were observed between amphetamine concentration in meconium and CNS stress. Conclusion Across cultures, prenatal MA exposure was associated with a similar neurobehavioral pattern of under arousal, low tone, poorer quality of movement and increased stress. PMID:20615464

  12. Amphetamines in the Treatment of Hyperkinetic Children

    Science.gov (United States)

    Grinspoon, Lester; Singer, Susan B.

    1973-01-01

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

  13. Analysis of amphetamine-type stimulants and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry.

    Science.gov (United States)

    Kuwayama, Kenji; Inoue, Hiroyuki; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Miyauchi, Seiji; Kamo, Naoki

    2008-05-01

    The aim of this work was to develop and validate a method for analysing amphetamine-type stimulants (ATSs) and their metabolites in plasma, urine and bile by liquid chromatography with a strong cation-exchange column-tandem mass spectrometry, and to apply it to the pharmacokinetic study of ATSs. 3,4-Methylenedioxymethamphetamine, methamphetamine, ketamine and their main metabolites, 4-hydroxy-3-methoxymethamphetamine, 3,4-methylenedioxyamphetamine, p-hydroxymethamphetamine, amphetamine and norketamine, were simultaneously quantified by the new method (50-5000 ng/ml). The coefficients of variation and the percent deviations for the eight compounds were in the range of 0.2 to 5.3% and -9.4 to +12.8%, respectively. The recoveries were over 90% in all biological samples tested. This method was effective for the separation and the identification of ATSs and their main metabolites having amine moieties in plasma, urine and bile, and was applicable to pharmacokinetic analysis of methamphetamine, ketamine and their main metabolites in biological samples. This analytical method should be useful for the pharmacokinetic analysis of ATSs.

  14. Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

    Science.gov (United States)

    Schindler, Charles W; Gilman, Joanne P; Panlilio, Leigh V; McCann, David J; Goldberg, Steven R

    2011-02-01

    The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.

  15. Methamphetamine

    Science.gov (United States)

    ... the risks of taking this medication.Do not sell, give away, or let anyone else take your ... Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by ...

  16. Functional and Structural Brain Changes Associated with Methamphetamine Abuse

    Directory of Open Access Journals (Sweden)

    Bruce R. Russell

    2012-10-01

    Full Text Available Methamphetamine (MA is a potent psychostimulant drug whose abuse has become a global epidemic in recent years. Firstly, this review article briefly discusses the epidemiology and clinical pharmacology of methamphetamine dependence. Secondly, the article reviews relevant animal literature modeling methamphetamine dependence and discusses possible mechanisms of methamphetamine-induced neurotoxicity. Thirdly, it provides a critical review of functional and structural neuroimaging studies in human MA abusers; including positron emission tomography (PET and functional and structural magnetic resonance imaging (MRI. The effect of abstinence from methamphetamine, both short- and long-term within the context of these studies is also reviewed.

  17. Analysis of amphetamines in urine with liquid-liquid extraction by capillary electrophoresis with simultaneous electrochemical and electrochemiluminescence detection.

    Science.gov (United States)

    Sun, Jinying; Xu, Xiaoyu; Wang, Chunyan; You, Tianyan

    2008-10-01

    Amphetamines including methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine were separated and detected by CE using simultaneous electrochemical (EC) and electrochemiluminescence (ECL) detection (CE-EC/ECL). Factors that influenced the separation and detection performance, such as the detection potential, the pH value and concentration of the running buffer, the separation voltage and the pH of the detection buffer, were investigated. LODs of 3.3x10(-8) mol/L (0.16 fmol), 1.6x10(-7) mol/L (0.78 fmol) and 3.3x10(-8) mol/L (0.16 fmol) were obtained for methamphetamine, 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine, respectively. For practical application, a liquid-liquid extraction with ethyl acetate procedure was developed for urine sample pretreatment and extraction efficiencies higher than 90% were obtained. The established simultaneous CE-EC/ECL was successfully applied for urine sample analysis.

  18. The Effect of Prenatal Methamphetamine Exposure on Attention as Assessed by Continuous Performance Tests: Results from the Infant Development, Environment, and Lifestyle (IDEAL) Study

    Science.gov (United States)

    Kiblawi, Zeina N.; Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; DellaGrotta, Sheri; Dansereau, Lynne M.; Neal, Charles; Lester, Barry

    2013-01-01

    Objective The purpose of this study is to assess for increased risk of attention deficit hyperactivity problem in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study. Methods IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa, OK; Des Moines, IA; Los Angeles, CA; and Honolulu, HI). Methamphetamine exposed subjects (n=204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched subjects (n=208) denied methamphetamine use and had a negative meconium screen. This analysis includes a subsample of 301 subjects that were administered the Conners’ Kiddie Continuous Performance Test (K-CPT) at age 5.5 years (153 exposed, 148 comparison). Hierarchical linear models adjusted for covariates tested exposure effects on K-CPT measures. Using the same covariates, logistic regression was used to determine the effect of exposure on the incidence of a positive ADHD confidence index score, defined as greater than 50%. Results There were no differences between the groups in omission or commission errors or reaction time for correct trials. However, methamphetamine exposure was associated with subtle differences in other outcomes predictive of ADHD, including increased slope of reaction time across blocks (p<0.001), increased variability in reaction time with longer interstimulus intervals (p<0.01), and increased likelihood of greater than 50% on the ADHD confidence index (OR 3.1, 95% CI 1.2–7.8; p=0.02). Conclusion Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at age 5.5 years. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring. PMID:23275056

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

    Science.gov (United States)

    Nicholi, Armand M., Jr.

    1984-01-01

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

  20. 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.

  1. 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.

  2. Screening for urinary amphetamine and analogs by capillary electrophoretic immunoassays and confirmation by capillary electrophoresis with on-column multiwavelength absorbance detection.

    Science.gov (United States)

    Ramseier, A; Caslavska, J; Thormann, W

    1998-11-01

    This paper characterizes competitive binding, electrokinetic capillary-based immunoassays for screening of urinary amphetamine (A) and analogs using reagents which were commercialized for a fluorescence polarization immunoassay (FPIA). After incubation of 25 microL urine with the reactants, a small aliquot of the mixture is applied onto a fused-silica capillary and unbound fluorescein-labeled tracer compounds are monitored by capillary electrophoresis with on-column laser-induced fluorescence detection. Configurations in presence and absence of micelles were investigated and found to be capable of recognizing urinary D-(+)-amphetamine at concentrations > about 80 ng/mL. Similar responses were obtained for racemic methamphetamine (MA) and 3,4-methylenedioxymethamphetamine (MDMA). The electrokinetic immunoassay data suggest that the FPIA reagent kit includes two immunoassay systems (two antibodies and two tracer molecules), one that recognizes MA and MDMA, and one that is geared towards monitoring of A. For confirmation analysis of urinary amphetamines and ephedrines, capillary electrophoresis in a pH 9.2 buffer and multiwavelength UV detection was employed. The suitability of the electrokinetic methods for screening and confirmation is demonstrated via analysis of patient and external quality control urines.

  3. 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.

  4. A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.

    Science.gov (United States)

    Gabor, K A; Charette, J R; Pietraszewski, M J; Wingfield, D J; Shim, J S; Millard, P J; Kim, C H

    2015-08-01

    Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.

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

    Science.gov (United States)

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

    2016-08-01

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

  6. Widespread increases in malondialdehyde immunoreactivity in dopamine-rich and dopamine-poor regions of rat brain following multiple, high doses of methamphetamine.

    Directory of Open Access Journals (Sweden)

    Kristen Ashley eHorner

    2011-05-01

    Full Text Available Treatment with multiple high doses of methamphetamine (METH can induce oxidative damage, including dopamine (DA-mediated reactive oxygen species (ROS formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu and substantia nigra pars compacta (SNpc. Malondialdehyde (MDA, a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg every 2h for 6h, sacrificed one week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir in the CPu, SNpc, cortex and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area (VTA and nucleus accumbens (NAc. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system.

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

    Science.gov (United States)

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

    2002-04-05

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

  8. Nasal Septum Perforation due to Methamphetamine abuse

    Directory of Open Access Journals (Sweden)

    Mehdi Bakhshaee

    2012-07-01

    Full Text Available Introduction: Spontaneous Perforation of the nasal septum is an uncommon condition. Nasal inhalation of substances such as cocaine has long been linked to this Perforation. Case Report: This report describes the case of a 46-year-old woman who was addicted to methamphetamine and who presented with perforation of the nasal septum.This is the first reported case of nasal septal necrosis linked to nasal inhalation of methamphetamine. Conclusions: Patient history and assurance regardingillegal drug consumption and abuse is a key point for fast and accurate diagnosis. The pathophysiology of drug-induced sinunasal disease and a review of the literature are also presented.

  9. 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.

  10. Methamphetamine Exposure: A Rural Early Intervention Challenge

    Science.gov (United States)

    Lester, Barry M.; Arria, Amelia M.; Derauf, Christian; Grant, Penny; LaGasse, Linda; Newman, Elana; Shah, Rizwan Z.; Stewart, Sara; Wouldes, Trecia

    2006-01-01

    In the Infant Development, Environment and Lifestyle (IDEAL) Study of methamphetamine (MA) effects on children, the authors screened approximately 27,000 newborn infants for MA exposure, and from that pool derived a sample of in utero MA-exposed children as well as a comparison group matched for other drug use and other factors. IDEAL measures…

  11. 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.

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  13. Antiviral function of grouper MDA5 against iridovirus and nodavirus.

    Science.gov (United States)

    Huang, Youhua; Yu, Yepin; Yang, Ying; Yang, Min; Zhou, Linli; Huang, Xiaohong; Qin, Qiwei

    2016-07-01

    Melanoma differentiation-associated gene 5 (MDA5) is a critical member of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family which can recognize viral RNA and enhances antiviral response in host cells. In this study, a MDA5 homolog from orange spotted grouper (Epinephelus coioides) (EcMDA5) was cloned, and its roles on grouper virus infection were characterized. The full-length EcMDA5 cDNA encoded a polypeptide of 982 amino acids with 74% identity with MDA5 homolog from rock bream (Oplegnathus fasciatus). Amino acid alignment analysis indicated that EcMDA5 contained three functional domains: two caspase activation and recruitment domain (CARDs), a DEAD box helicase-like (DExDc) domain, a helicase superfamily C-terminal domain (HELICc), and a C-terminal regulatory domain (RD). Upon challenge with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C), the transcript of EcMDA5 was significantly up-regulated especially at the early stage post-injection. Under fluorescence microscopy, we observed that EcMDA5 mostly localized in the cytoplasm of grouper spleen (GS) cells. Interestingly, during virus infection, the distribution pattern of EcMDA5 was significantly altered in SGIV infected cells, but not in red spotted grouper nervous necrosis virus (RGNNV) infected cells, suggested that EcMDA5 might interact with viral proteins during SGIV infection. The ectopic expression of EcMDA5 in vitro obviously delayed virus infection induced cytopathic effect (CPE) progression and significantly inhibited viral gene transcription of RGNNV and SGIV. Moreover, overexpression of EcMDA5 not only significantly increased interferon (IFN) and IFN-stimulated response element (ISRE) promoter activities in a dose dependent manner, but also enhanced the expression of IRF3, IRF7 and TRAF6. In addition, the transcription level of the proinflammatory factors, including TNF-α, IL-6 and IL-8 were differently altered by EcMDA5 overexpression during SGIV or

  14. Towards an MDA-based development methodology for distributed applications

    NARCIS (Netherlands)

    Gavras, A.; Belaunde, M.; Ferreira Pires, L.; Andrade Almeida, J.P.; van Sinderen, M.J.; Ferreira Pires, L.

    2004-01-01

    This paper proposes a development methodology for distributed applications based on the principles and concepts of the Model-Driven Architecture (MDA). The paper identifies phases and activities of an MDA-based development trajectory, and defines the roles and products of each activity in accordance

  15. On the Notion of Abstract Platform in MDA Development

    NARCIS (Netherlands)

    Almeida, João Paulo; Dijkman, Remco; Sinderen, van Marten; Ferreira Pires, Luis

    2004-01-01

    Although platform-independence is a central property in MDA models, the study of platform-independence has been largely overlooked in MDA. As a consequence, there is a lack of guidelines to select abstraction criteria and modelling concepts for platform-independent design. In addition, there is litt

  16. Toxicity of methamphetamine and the protection of tatinol

    Institute of Scientific and Technical Information of China (English)

    LiJ; WangX

    2002-01-01

    To investigate the neurotoxicity of methamphetamine and the neuroprotection of tatinol,an acute toxic dosing model in rat was established by intraperitoneal injection of methamphetamine,and being treated with tatinol.HE and silver staining,observed with light microscope;apoptosis was detected by TUNEL.The results showed that methamphetamine may damage brain and induce apoptosis,tatinol could protect against apoptosis.

  17. New Meconium Biomarkers of Prenatal Methamphetamine Exposure Increase Identification of Affected Neonates

    Science.gov (United States)

    Gray, Teresa R.; Kelly, Tamsin; LaGasse, Linda L.; Smith, Lynne M.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Haning, William; Grotta, Sheri Della; Strauss, Arthur; Lester, Barry M.; Huestis, Marilyn A.

    2010-01-01

    BACKGROUND Prenatal methamphetamine (MAMP) exposure is poorly reflected in neonatal meconium. Often, maternal self-reported MAMP use is not corroborated by positive results in amphetamines immunoassays of meconium, and even if initial test results are positive, they frequently are not confirmed for MAMP or amphetamine (AMP) by chromatographic analysis. The presence of the MAMP metabolites p-hydroxymethamphetamine (pOHMAMP), p-hydroxyamphetamine (pOHAMP), and norephedrine (NOREPH) in meconium may improve the identification of MAMP- and AMP-exposed neonates. METHODS Immunoassay-positive and -negative meconium samples were subjected to liquid chromatography–tandem mass spectrometric reanalysis for these recently identified metabolites. RESULTS pOHAMP and NOREPH were detected only when MAMP and/or AMP were present and thus do not appear to be promising biomarkers of prenatal MAMP exposure. pOHMAMP, in contrast, identified 6 additional neonates whose mothers reported MAMP exposure, yet had a meconium sample screened as negative; pOHMAMP was more likely to be present if maternal MAMP use continued into the third trimester. Although the pOHMAMP results for meconium samples corroborated the maternal self-reports, the confirmation rate for positive meconium screening results did not improve with the inclusion of these new biomarkers. CONCLUSIONS pOHMAMP identified additional MAMP-exposed neonates; therefore, MAMP, AMP, and pOHMAMP should be included in meconium chromatographic analyses. To maximize the identification of MAMP-exposed children requires improvement in immunoassay screening tests to reduce false-negative and false-positive results. Additional research will help clarify which AMP-related compounds, if any, contribute to unconfirmed positive results in screening tests. Furthermore, nonamphetamine compounds endogenous to the complex meconium matrix also may cross-react, making chromatographic confirmation of screening results essential. PMID:20185623

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

    Directory of Open Access Journals (Sweden)

    Masoome Eivazi

    2016-03-01

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

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

    Science.gov (United States)

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

    2015-08-01

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

  20. Duration of detection of methamphetamine in hair after abstinence.

    Science.gov (United States)

    Suwannachom, Natiprada; Thananchai, Thiwaphorn; Junkuy, Anongphan; O'Brien, Timothy E; Sribanditmongkol, Pongruk

    2015-09-01

    Researchers in the field of hair analysis have known for at least two decades that test results for many chemical compounds remain positive for a considerable period of time after subjects have reported cessation of use. These findings were generally based on small sample populations or individual case studies. Within the last decade, hair analyses of larger populations have investigated the phenomenon of residual positives in abstinent individuals in order to determine the period of time required for various compounds to present negative hair test results at internationally accepted cutoff levels. Such data has primarily been used to establish guidelines for retesting former abusers of illicit drugs in order to evaluate claims of abstinence. To date, research has focused on cocaine and opiates. The present study is the first to examine the duration of detection of methamphetamine (MA) and its metabolite amphetamine (AP) in the hair of chronic MA users who recently ceased their consumption of the drug. The study population (n=63) consisted of inpatients at a hospital drug rehabilitation program in Chiang Mai, Thailand. Drug taking behavior was collected by personal interview at the time of enrollment. Subjects provided hair samples at approximately monthly intervals for MA and AP analysis by gas chromatography-mass spectrometry at 0.2ng/mg cutoff levels. The correlation of baseline MA and AP concentrations in hair at the beginning of abstinence with corresponding duration of detection indicated great individual variability for the rate of clearance of MA and AP from hair. In regard to duration of detection, the majority of chronic MA users remained MA positive for up to about 90 days of reported abstinence, but by 120 days, the detection rate had fallen to about 16%. All subjects tested negative for MA after 153 days of abstinence. For AP, the limit of the duration of detection was reached at 106 days. With the adoption of a margin of safety to compensate for

  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. Effects of methamphetamine dependence and HIV infection on cerebral morphology

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.;

    2005-01-01

    OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age- an...

  3. Radiometric Testing of Magnesium Diboride Array (MDA) Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The objective is to develop a 2-Dimensional Far Infra-Red Magnesium Diboride Array (2D FIR MDA) to use in NASA’s future planetary exploration instruments. The...

  4. Amphetamine enhances retrieval following diverse sources of forgetting.

    Science.gov (United States)

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

    1988-01-01

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

  5. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    OpenAIRE

    Panikkath, Ragesh; Panikkath, Deepa

    2016-01-01

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

  6. Amphetamine-related ischemic colitis causing gastrointestinal bleeding

    Science.gov (United States)

    Panikkath, Deepa

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-09-06

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

  8. Correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual methamphetamine users.

    Science.gov (United States)

    Semple, Shirley J; Strathdee, Steffanie A; Zians, Jim; Patterson, Thomas L

    2011-01-01

    While many studies have examined correlates of trading sex for money, few have examined factors associated with exclusive trading of sex for drugs. We identified sociodemographic, behavioral, and psychological correlates of trading sex for methamphetamine in a sample of HIV-negative heterosexual men and women who were enrolled in a sexual risk reduction intervention in San Diego, California. Of 342 participants, 26% overall (21% of males and 31% of females) reported trading sex for methamphetamine in the past two months. Multiple logistic regression analysis revealed that recently trading sex for methamphetamine was independently associated with being female, homeless, binging on methamphetamine, sexual victimization in the past two months, engaging in anal sex 24 or more times in the past two months, and higher sexual compulsivity scores. Effective interventions for this high-risk population should consider gender-focused counseling for sexual abuse, motivational enhancement therapy, social-cognitive skills training, as well as enhanced access and utilization of social services, including drug treatment.

  9. Identification of Prenatal Amphetamines Exposure by Maternal Interview and Meconium Toxicology in the Infant Development, Environment and Lifestyle (IDEAL) Study

    Science.gov (United States)

    Gray, Teresa R.; LaGasse, Linda L.; Smith, Lynne M.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia M.; Della Grotta, Sheri A.; Strauss, Arthur; Haning, William F.; Lester, Barry M.; Huestis, Marilyn A.

    2009-01-01

    The Infant Development Environment and Lifestyle (IDEAL) study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Materials and Methods Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry (GCMS). Results The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by GCMS. Tobacco exposure was equally detected by immunoassay cotinine screen and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use, frequency or route of MAMP use. Discussion Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women ceased MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Conclusion Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers. PMID:19935364

  10. Identification and quantitation of amphetamines, cocaine, opiates, and phencyclidine in oral fluid by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Fritch, Dean; Blum, Kristen; Nonnemacher, Sheena; Haggerty, Brenda J; Sullivan, Matthew P; Cone, Edward J

    2009-01-01

    Analytical methods for measuring multiple licit and illicit drugs and metabolites in oral fluid require high sensitivity, specificity, and accuracy. With the limited volume available for testing, comprehensive methodology is needed for simultaneous measurement of multiple analytes in a single aliquot. This report describes the validation of a semi-automated method for the simultaneous extraction, identification, and quantitation of 21 analytes in a single oral fluid aliquot. The target compounds included are amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxy-amphetamine, 3,4-methylenedioxyethylamphetamine, pseudoephedrine, cocaine, benzoylecgonine, codeine, norcodeine, 6-acetylcodeine, morphine, 6-acetylmorphine, hydrocodone, norhydrocodone, dihydrocodeine, hydromorphone, oxycodone, noroxycodone, oxymorphone, and phencyclidine. Oral fluid specimens were collected with the Intercept device and extracted by solid-phase extraction (SPE). Drug recovery from the Intercept device averaged 84.3%, and SPE extraction efficiency averaged 91.2% for the 21 analytes. Drug analysis was performed by liquid chromatography-tandem mass spectrometry in the positive electrospray mode using ratios of qualifying product ions within +/-25% of calibration standards. Matrix ion suppression ranged from -57 to 8%. The limit of quantitation ranged from 0.4 to 5 ng/mL using 0.2 mL of diluted oral fluid sample. Application of the method was demonstrated by testing oral fluid specimens from drug abuse treatment patients. Thirty-nine patients tested positive for various combinations of licit and illicit drugs and metabolites. In conclusion, this validated method is suitable for simultaneous measurement of 21 licit and illicit drugs and metabolites in oral fluid.

  11. Identification of prenatal amphetamines exposure by maternal interview and meconium toxicology in the Infant Development, Environment and Lifestyle (IDEAL) study.

    Science.gov (United States)

    Gray, Teresa R; LaGasse, Linda L; Smith, Lynne M; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia M; Della Grotta, Sheri A; Strauss, Arthur; Haning, William F; Lester, Barry M; Huestis, Marilyn A

    2009-12-01

    The Infant Development Environment and Lifestyle study is investigating the effects of prenatal methamphetamine (MAMP) exposure on infant and child development; potential concurrent exposure to cannabis and tobacco also are evaluated. Maternal self-reported drug use and/or meconium toxicology results defined drug exposure status. It is unclear how the frequency, duration, and magnitude of maternal MAMP exposure affect qualitative and quantitative meconium results. Interviews regarding maternal drug use were collected shortly after birth; meconium specimens were screened for amphetamines, cannabis, and cotinine by immunoassay and confirmed by gas chromatography mass spectrometry. The majority of MAMP- and cannabis-exposed infants were identified by maternal interview alone. Meconium tests were more likely to be positive if the mother reported MAMP and cannabis use, particularly in the third trimester. Less than half of immunoassay-positive amphetamines (31.0%) and cannabis (17.9%) meconium results were confirmed by gas chromatography mass spectrometry. Tobacco exposure was equally detected by immunoassay cotinine screening and maternal report. Meconium concentrations did not correlate with maternal self-report status or trimester of use or frequency or route of MAMP use. Maternal self-report was more sensitive than meconium testing for identifying MAMP and cannabis-exposed neonates; however, the timing of drug exposure may influence meconium toxicology results. Most women stopped MAMP and cannabis use before the third trimester. In the first trimester, meconium has not yet formed, and based on our recent results for opiates and cocaine, drug use in the second trimester appears to be poorly reflected in meconium. Low confirmation rates in meconium reinforce the need for confirmatory testing following positive screening results and additional research to identify alternative biomarkers.

  12. A new mixed mode solid phase extraction strategy for opioids, cocaines, amphetamines and adulterants in human blood with hybrid liquid chromatography tandem mass spectrometry detection.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam

    2011-04-05

    A rapid method has been developed to analyse morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgonine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, methadone, phenethylamine and levamisole in human blood. Blood samples were cleaned up using mixed mode solid phase extraction using Evolute™ CX solid phase extraction cartridges and the sample aliquots were analysed by hybrid triple quadrupole linear ion trap (QTRAP) mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35 ± 15 in positive mode and MRM ratios. The method was validated in blood, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra. Deuterated analogues of analytes were used as internal standards for quantitation where possible. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines, amphetamines and adulterants in forensic cases of crime offenders, abusers or victims in the Republic of Ireland.

  13. Studies on the metabolism and toxicological detection of the amphetamine-like anorectic mefenorex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay.

    Science.gov (United States)

    Kraemer, T; Vernaleken, I; Maurer, H H

    1997-11-21

    Studies on the metabolism and on the toxicological analysis of mefenorex [R,S-N-(3-chloropropyl)-alpha-methylphenethylamine, MF] using gas chromatography-mass spectrometry (GC-MS) and fluorescence polarization immunoassay (FPIA) are described. The metabolites were identified in urine samples of volunteers by GC-MS. Besides MF, thirteen metabolites including amphetamine (AM) could be identified and three partially overlapping metabolic pathways could be postulated. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for MF and 100 ng/ml for AM). Excretion studies showed, that only AM but neither MF nor its specific metabolites were detectable between 32 and 68 h after ingestion of 80 mg of MF. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 68 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.

  14. Against professional advice: treatment attrition among pregnant methamphetamine users

    Directory of Open Access Journals (Sweden)

    Terplan M

    2011-10-01

    Full Text Available Brianna Lindsay1, Jennifer Albrecht1, Mishka Terplan1,21Department of Epidemiology and Public Health, University of Maryland, 2Department of Obstetrics, Gynecology, and Reproductive Science, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Pregnant methamphetamine users who leave substance use treatment against professional advice may be at risk of poorer health outcomes. To examine the hypothesis that methamphetamine use during pregnancy may be associated with leaving substance use treatment against professional advice, the 2006 Treatment Episode Data Set was analyzed. A logistic regression adjusting for age, race, service setting, prior substance abuse treatment, criminal justice referral, and education was conducted. Inclusion criteria were met by 18,688 pregnant admissions; 26.4% identified methamphetamines as their primary substance of use. Frequency of use was identified as an effect modifier, therefore results were stratified by less than weekly use and weekly or more use. Methamphetamine use was significantly associated with leaving treatment against professional advice regardless of usage level. However, the odds of leaving treatment were greater among women using methamphetamine less than weekly. Further investigation into this association may be warranted due to the complications that may result from methamphetamine use during pregnancy.Keywords: pregnancy, methamphetamines, treatment, attrition

  15. Pengaruh Timbal (Pb Terhadap Kadar MDA Serum Tikus Putih Jantan

    Directory of Open Access Journals (Sweden)

    Endrinaldi .

    2014-09-01

    Full Text Available AbstrakTimbal (Pb merupakan logam berat bersifat toksik yang konsentrasinya di lingkungan saat ini dipandang sebagai zat berbahaya. Pb dalam bentuk senyawa berasal dari pembakaran bahan bakar kendaraan bermotor, emisi industry dan dari penggunaan cat bangunan yang mengandung Pb. Toksisitas Pb menghambat enzim yang berperan sebagai antioksidan dan merusak sel hati.Tujuan studi ini adalah untuk melihat pengaruh timbal (Pb terhadap kadar malondialdehid (MDA tikus putih jantan. Desain penelitian ini adalah eksperimental menggunakan 25 ekor tikus putih jantan yang dibagi menjadi lima kelompok, yaitu kelompok kontrol, dan kelompok perlakuan dengan pemberian Pb asetat dengan dosis konsentrasi 5, 10, 20 dan 40 mg/kg BB selama 26 hari.Hasil penelitian menunjukkan terjadinya peningkatan rerata kadar MDA serum secara bermakna (p < 0,05, setelah pemberian Pb asetat selama 26 hari. Peningkatan kadar MDA secara bermakna terjadi antara kelompok kontrol dibandingkan dengan kelompok tikus yang diberi dosis 5, 10, 20 dan 40 mg/kg BB.Kesimpulan yang dapat diambil dari studi ini adalah bahwa pemberian Pb asetat meningkatkan kadar MDA serum tikus.Kata kunci: Pb asetat, MDAAbstractLead (Pb is atoxi cheavy metal concentrationsin the environment are now seenas a dangerous substance. Pb in the form of compounds derived from burningmotor vehicle fuel. Pb toxicityinhibitsan enzyme that acts as an antioxidant and liver cell damage.The purpose of this study was to observe the effect of lead (Pb on levels of malondialdehyde (MDA male whiterats. Experimental research design was used 25 white male rats were divided into five groups, namely the control group and the group treated with the administration of Pb acetate at a dose concentration of 5, 10, 20, and 40 mg / kg body weight for 26 days.The results showed an average increase in level of MDA, after administration of Pb acetate for 26 days were significantly (p <0.05. Increase in level of MDA of serum were significantly (p

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

    Science.gov (United States)

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

    2015-04-01

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

  17. 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.

  18. [Immunohistochemical study on the mechanism of excretion of methamphetamine].

    Science.gov (United States)

    Kajitani, A; Kaiho, M; Mori, A; Okada, Y; Mukaida, M; Ishiyama, I

    1989-06-01

    Many methods of analysis are available to the forensic toxicologist for determining the amount of methamphetamine within human tissues, but few have the potential of histochemistry for enabling the precise site of excretion of methamphetamine to be defined. We have established a method for the demonstration of methamphetamine by immunohistochemistry, and applied this method for showing morphologically the disposition of methamphetamine. The following cells in the tissues of methamphetamine-intoxicated mice gave a strong positive reaction of the localization, which was thought to be the histological evidence of excretion of this drug: epithelial cells of the distal part of the renal tubule and of the collecting tubule, transitional epithelial cells of the bladder, liver parenchymal cells, epithelial cells of the striated duct of the salivary gland, parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine, secretory cells and part of epithelial cells of the ductal portion of the sweat gland, alveolar cells of the mammary gland, secretory cells of the sebaceous gland and hair medulla and cortex. These results indicated passive diffusion of methamphetamine across membranes of the cells of the distal tubule and collecting tubule of the kidney, of the bladder and of the striated duct of the salivary gland. In the parietal cells of the gastric gland, part of epithelial cells of the distal portion of the large intestine and secretory cells of the sweat gland, methamphetamine was thought to be stored and subsequently released. In the mammary gland, methamphetamine was found to be combined with casein and excreted by exocytosis. Accumulation of methamphetamine in the hair was supposed to be chiefly due to the penetration of this drug derived from tissue fluid and sebum.

  19. Desorption of a methamphetamine surrogate from wallboard under remediation conditions

    Science.gov (United States)

    Poppendieck, Dustin; Morrison, Glenn; Corsi, Richard

    2015-04-01

    Thousands of homes in the United States are found to be contaminated with methamphetamine each year. Buildings used to produce illicit methamphetamine are typically remediated by removing soft furnishings and stained materials, cleaning and sometimes encapsulating surfaces using paint. Methamphetamine that has penetrated into paint films, wood and other permanent materials can be slowly released back into the building air over time, exposing future occupants and re-contaminating furnishings. The objective of this study was to determine the efficacy of two wallboard remediation techniques for homes contaminated with methamphetamine: 1) enhancing desorption by elevating temperature and relative humidity while ventilating the interior space, and 2) painting over affected wallboard to seal the methamphetamine in place. The emission of a methamphetamine surrogate, N-isopropylbenzylamine (NIBA), from pre-dosed wallboard chambers over 20 days at 32 °C and two values of relative humidity were studied. Emission rates from wallboard after 15 days at 32 °C ranged from 35 to 1400 μg h-1 m-2. Less than 22% of the NIBA was removed from the chambers over three weeks. Results indicate that elevating temperatures during remediation and latex painting of impacted wallboard will not significantly reduce freebase methamphetamine emissions from wallboard. Raising the relative humidity from 27% to 49% increased the emission rates by a factor of 1.4. A steady-state model of a typical home using the emission rates from this study and typical residential building parameters and conditions shows that adult inhalation reference doses for methamphetamine will be reached when approximately 1 g of methamphetamine is present in the wallboard of a house.

  20. 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.

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

    Science.gov (United States)

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

    2012-10-01

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

  2. Terahertz spectroscopic investigation of methylenedioxy amphetamine

    Science.gov (United States)

    Wang, Guangqin; Shen, Jingling

    2008-03-01

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

  3. Aplicando UML y DSL en el enfoque MDA

    OpenAIRE

    2010-01-01

    El enfoque MDA (Model Driven Architecture) está basado en dos elementos: los modelos y las transformaciones, mediante los cuales se dirige el proceso de desarrollo. Cada transformación arrojará un resultado más detallado hasta obtener el código necesario para implementar la solución en una plataforma específica. En este paper se plantea la utilización de dos lenguajes de modelado aplicados al enfoque de MDA. Un lenguaje de propósito general como lo es UML (Unified Modeling Language) aplicado ...

  4. Medico-legal aspect of amphetamine-related deaths

    Directory of Open Access Journals (Sweden)

    Karol Kula

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Vo K

    2015-01-01

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

  6. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    Directory of Open Access Journals (Sweden)

    Joshua L. Fenderson

    2013-01-01

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

  7. Amphetamine positive urine toxicology screen secondary to atomoxetine.

    Science.gov (United States)

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

    2013-01-01

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

  8. 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.

  9. Determination of amphetamines in human urine by liquid chromatography with fluorimetric detection using a solid-phase extraction procedure.

    Science.gov (United States)

    Bugamelli, Francesca; Mandrioli, Roberto; Cavallini, Annalisa; Baccini, Cesare; Conti, Matteo; Raggi, Maria Augusta

    2006-10-01

    A precise and feasible HPLC method has been developed for the analysis of amphetamine (AMPH), methamphetamine (MAMPH) and methylenedioxymethamphetamine (MDMA, ecstasy) in human urine. A chromatographic run on a C8 Genesis (150 mm x 4.6 mm, 5 microm) column maintained at 30 degrees C lasts about 17 min, using a mobile phase composed of ACN (12%) and a pH 2.5 phosphate buffer (88%) containing 0.3% triethylamine. Mirtazapine was used as the internal standard. Good linearity was found in the 100-2000 ng/mL concentration range for AMPH and MAMPH and in the 12-2000 ng/mL concentration range for MDMA. The pretreatment of urine samples was carried out by means of a careful SPE procedure on C2 cartridges. The extraction yields were very satisfactory for all analytes, with average values greater than 97%. The leading conditions allowed the determination of AMPH, MAMPH and MDMA with satisfactory precision and accuracy. The method has been successfully applied to the determination of the analytes in urine of AMPH users.

  10. Effects of methamphetamine dependence and HIV infection on cerebral morphology

    DEFF Research Database (Denmark)

    Jernigan, Terry Lynne; Gamst, Abthony C; Archibald, Sarah L.;

    2005-01-01

    OBJECTIVE: The authors examined the separate and combined effects of methamphetamine dependence and HIV infection on brain morphology. METHOD: Morphometric measures obtained from magnetic resonance imaging of methamphetamine-dependent and/or HIV-positive participants and their appropriate age......- and education-matched comparison groups were analyzed. Main effects of age, HIV infection, methamphetamine dependence, and the interactions of these factors were examined in analyses of cerebral gray matter structure volumes. RESULTS: Independent of the effect of age, HIV infection was associated with reduced...... volumes of cortical, limbic, and striatal structures. There was also some evidence of an interaction between age and HIV infection such that older HIV-positive participants suffered disproportionate loss. Methamphetamine dependence was surprisingly associated with basal ganglia and parietal cortex volume...

  11. Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

    OpenAIRE

    Hodges, A.B; Ladenheim, B.; McCoy, M T; Beauvais, G; Cai, N; Krasnova, I. N.; Cadet, J.L.

    2011-01-01

    Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dos...

  12. 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.

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

    Science.gov (United States)

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

    2008-10-01

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

  14. Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum.

    Science.gov (United States)

    Angoa-Pérez, Mariana; Kane, Michael J; Francescutti, Dina M; Sykes, Katherine E; Shah, Mrudang M; Mohammed, Abiy M; Thomas, David M; Kuhn, Donald M

    2012-03-01

    Mephedrone (4-methylmethcathinone) is a β-ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the United States and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge-like regimen of mephedrone (4 × 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum.

  15. The Comparsion of the Efficacy of Group Psychotherapy Based on Acceptance and Commitment Therapy, and Mindfulness on Craving and Cognitive Emotion Regulation in Methamphetamine Addicts

    Directory of Open Access Journals (Sweden)

    Ahmadreza Kiani

    2013-01-01

    Full Text Available Aim: Today, third wave therapies in psychotherapy shift their attention from challenging cognitions to awareness and acceptance of feelings, emotions, cognitions and behaviors. Therefore, this research aimed to compare of efficacy of group psychotherapy based on acceptance and commitment therapy, with mindfulness on craving and cognitive emotion regulation in methamphetamine addicts. Method: Research method was semi experimental research design with pre-post test and follow up. The population of research was included all of methamphetamine addicts in baharestan, Isfahan. Drug abusers was 34 participants that refered to addiction rehabilitation centers and selected by snowball sampling and finaly divided to 2groups by radomization (acceptance and commitment therapy group and mindfulness groups. Each groups recieved treatment in 12 sessions (At First 2 sessions per week and at last 1 session per week. Two groups assessed by craving test (Ekhtiary, 1387 and cognitive emotion regulation (garnefski et al, 2002, in pretest, post test and follow up. Results: The results showed that two treatment groups had significant effect on craving intensity in post test and follow up. In addition, there was no significant difference in comparing of the efficacy of these two treatments on cognitive emotion regulation and it means that both two traetments had same effect on cognitive emotion regulatin. Conclusion: we can say that acceptance and commitmet therapy and mindfulnesshave effect on reduction psychopathology from using amphetamines due to same theraputic factors.

  16. Solution-phase synthesis of a muramyl dipeptide analogue MDA

    Institute of Scientific and Technical Information of China (English)

    Nan Zhao; Yao Ma; Gang Liu

    2011-01-01

    The solution-phase synthesis of a muramyl dipeptide (MDP) analogue of Nα- [4-chlorocinnamoyl-L-alanyl-D-isoglutaminyl]-L-lysine (MDA, 2) is reported that possesses the features of easy feasibility, safety and low cost in large scale of synthesis.

  17. Harvesting software systems for MDA-based reengineering

    NARCIS (Netherlands)

    Reus, T.; Geers, H.; Van Deursen, A.

    2006-01-01

    In this paper we report on a feasibility study in reengineering legacy systems towards a model-driven architecture (MDA). Steps in our approach consist of (1) parsing the source code of the legacy system according to a grammar; (2) mapping the abstract syntax trees thus obtained to a grammar model t

  18. Bupropion interference with immunoassays for amphetamines and LSD.

    Science.gov (United States)

    Vidal, Christian; Skripuletz, Thomas

    2007-06-01

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

  19. [The randomized controlled trial of the prison-based Japanese Matrix Program (J-MAT) for methamphetamine abusers].

    Science.gov (United States)

    Harada, Takayuki

    2012-12-01

    Methamphetamine use is subject to severe criminal punishment in Japan and approximately 22% of the prison population were confined for violations of the stimulants control law in 2009. Although the high recidivism rate is also a problem, no systematic treatment has been conducted in prison. Therefore, the development of the prison-based treatment program is necessary. In this study, the prison-based program was developed based on the Matrix Model, which is the cognitive-behavioral treatment for amphetamine users developed in the US. The program was tailored in order to address the treatment needs of the Japanese amphetamine users considering Japanese culture and the prison climate. The randomized controlled trial was conducted in order to evaluate the effectiveness the Japanese Matrix program (J-MAT). 60 prisoners were randomly assigned either to the J-MAT or the control groups and those who in the J-MAT group received the program once a week for 12 weeks. The abstinence rate could not be used as the outcome measure because the participants could not be followed after the release from prison due to the legal reasons. Therefore, the psychological variables including coping skills, self-efficacy and motivation were used as outcome measures, which are considered as the important predictive factors of abstinence. 93.3% of the J-MAT participants completed the program. The coping skills of the treated prisoners were improved significantly after treatment comparing to the control (F (1, 27) = 9.03, p effectiveness of the J-MAT because both treatment completion and coping skills are powerful predictors of abstinence. Further study is required and in which the participants should be followed after the completion of treatment in order to compare the relapse rates between the groups and to measure the long-term treatment gain.

  20. Motor and Cognitive Outcomes Through Three Years Of Age In Children Exposed To Prenatal Methamphetamine

    Science.gov (United States)

    Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Haning, William; Arria, Amelia; Huestis, Marilyn; Strauss, Arthur; Grotta, Sheri Della; Dansereau, Lynne M.; Lin, Hai; Lester, Barry M.

    2010-01-01

    Background Methamphetamine (MA) use among pregnant women is an increasing problem in the United States. The impact of prenatal MA exposure on development in childhood is unknown. Objective To examine the effects of prenatal MA exposure on motor and cognitive development in children at 1, 2, and 3 years of age. Design/Methods IDEAL enrolled 412 mother-infant pairs at four sites (Tulsa OK, Des Moines IA, Los Angeles CA, and Honolulu HI). MA subjects (n=204) were identified by self-report or GC/MS confirmation of amphetamine and metabolites in infant meconium. Comparison subjects (n=208) were matched (race, birth weight, maternal education, type of insurance), denied amphetamine use, and had a negative meconium screen. Both groups included prenatal alcohol, tobacco and marijuana use, but excluded use of opiates, lysergic acid diethylamide, phencyclidine or cocaine only. The Peabody Developmental Motor Scales (PDMS-2) were administered to the infants at the 1 and 3 year visits. This analysis includes a subsample (n=350) of the IDEAL study with completed 1 and/or 3 year visits (n= 330 and 281, respectively). At each annual visit we also conducted the Bayley Scales of Infant Development (BSID-II) as a general evaluation of mental and motor development. The BSID-II analysis includes a subsample (n=356) of the IDEAL study with completed 1, 2, and/or 3 year visits (n= 331, 288, and 278 respectively). GLM analysis conducted on the PDMS-2 and BSID-II examined the effects of MA exposure and heavy MA exposure (≥3 days of use/week), with and without covariates. Longitudinal analyses were used to examine the effects of MA exposure on changes in motor and cognitive performance over time. Results Heavy MA exposure was associated with significantly lower grasping scores than some and no use at 1 year (P = 0.018). In longitudinal analysis, lower grasping scores associated with any MA exposure and heavy exposure persisted to 3 years. There were no effects of MA exposure, including

  1. 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.

  2. Impact of methamphetamine on infection and immunity

    Directory of Open Access Journals (Sweden)

    Sergio A Salamanca

    2015-01-01

    Full Text Available The prevalence of methamphetamine (METH use is estimated at ~35 million people worldwide, with over 10 million users in the United States. METH use elicits a myriad of social consequences and the behavioral impact of the drug is well understood. However, new information has recently emerged detailing the devastating effects of METH on host immunity, increasing the acquisition of diverse pathogens and exacerbating the severity of disease. These outcomes manifest as modifications in protective physical and chemical defenses, pro-inflammatory responses, and the induction of oxidative stress pathways. Through these processes, significant neurotoxicities arise, and, as such, chronic abusers with these conditions are at a higher risk for heightened consequences. METH use also influences the adaptive immune response, permitting the unrestrained development of opportunistic diseases. In this review, we discuss recent literature addressing the impact of METH on infection and immunity, and identify areas ripe for future investigation.

  3. A DN-mda5 Transgenic Zebrafish 1 Model Demonstrates that Mda5 Plays an Important Role in Snakehead Rhabdovirus Resistance

    Science.gov (United States)

    Gabor, KA; Charette, JR; Pietraszewski, MJ; Wingfield, DJ; Shim, JS; Millard, PJ; Kim, CH

    2015-01-01

    Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. PMID:25634485

  4. Regulation of dopamine transporter trafficking by intracellular amphetamine

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  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. ANN expert system screening for illicit amphetamines using molecular descriptors

    Science.gov (United States)

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

    2007-05-01

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

  7. Amphetamines modulate prefrontal γ oscillations during attention processing.

    Science.gov (United States)

    Franzen, John D; Wilson, Tony W

    2012-08-22

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

  8. Prevalence of nonmedical methamphetamine use in the United States

    Directory of Open Access Journals (Sweden)

    Barchha Nina

    2008-07-01

    Full Text Available Abstract Background Illicit methamphetamine use continues to be a public health concern in the United States. The goal of the current study was to use a relatively inexpensive methodology to examine the prevalence and demographic correlates of nonmedical methamphetamine use in the United States. Methods The sample was obtained through an internet survey of noninstitutionalized adults (n = 4,297 aged 18 to 49 in the United States in 2005. Propensity weighting methods using information from the U.S. Census and the 2003 National Survey on Drug Use and Health (NSDUH were used to estimate national-level prevalence rates. Results The overall prevalence of current nonmedical methamphetamine use was estimated to be 0.27%. Lifetime use was estimated to be 8.6%. Current use rates for men (0.32% and women (0.23% did not differ, although men had a higher 3-year prevalence rate (3.1% than women (1.1%. Within the age subgroup with the highest overall methamphetamine use (18 to 25 year olds, non-students had substantially higher methamphetamine use (0.85% current; 2.4% past year than students (0.23% current; 0.79% past year. Methamphetamine use was not constrained to those with publicly funded health care insurance. Conclusion Through the use of an internet panel weighted to reflect U.S. population norms, the estimated lifetime prevalence of methamphetamine use among 18 to 49 year olds was 8.6%. These findings give rates of use comparable to those reported in the 2005 NSDUH. Internet surveys are a relatively inexpensive way to provide complimentary data to telephone or in-person interviews.

  9. INCORPORATING AGILE WITH MDA CASE STUDY: ONLINE POLLING SYSTEM

    Directory of Open Access Journals (Sweden)

    Pritha Guha

    2011-11-01

    Full Text Available Nowadays agile software development is used in greater extend but for small organizations only, whereasMDA is suitable for large organizations but yet not standardized. In this paper the pros and cons ofModel Driven Architecture (MDA and Extreme programming have been discussed. As both of them havesome limitations and cannot be used in both large scale and small scale organizations a new architecturehas been proposed. In this model it is tried to opt the advantages and important values to overcome thelimitations of both the software development procedures. In support to the proposed architecture theimplementation of it on Online Polling System has been discussed and all the phases of softwaredevelopment have been explained.

  10. BDNF deficiency and young-adult methamphetamine induce sex-specific effects on prepulse inhibition regulation

    Directory of Open Access Journals (Sweden)

    Elizabeth E Manning

    2013-06-01

    Full Text Available Brain-derived neurotrophic factor (BDNF has been implicated in the pathophysiology of schizophrenia, yet its role in the development of specific symptoms is unclear. Methamphetamine (METH users have an increased risk of psychosis and schizophrenia, and METH-treated animals have been used extensively as a model to study the positive symptoms of schizophrenia. We investigated whether METH treatment in BDNF heterozygous mutant mice (HET has cumulative effects on sensorimotor gating, including the disruptive effects of psychotropic drugs. BDNF HETs and WT littermates were treated during young-adulthood with METH and, following a two-week break, prepulse inhibition (PPI was examined. At baseline, BDNF HETs showed reduced PPI compared to WT mice irrespective of METH pre-treatment. An acute challenge with amphetamine (AMPH disrupted PPI but male BDNF HETs were more sensitive to this effect, irrespective of METH pre-treatment. In contrast, female mice treated with METH were less sensitive to the disruptive effects of AMPH, and there were no effects of BDNF genotype. Similar changes were not observed in the response to an acute apomorphine or MK-801 challenge. These results show that genetically-induced reduction of BDNF caused changes in a behavioural endophenotype relevant to the positive symptoms of schizophrenia. However, major sex differences were observed in the effects of a psychotropic drug challenge on this behaviour. These findings suggest sex differences in the effects of BDNF depletion and METH treatment on the monoamine signaling pathways that regulate PPI. Given that these same pathways are thought to contribute to the expression of positive symptoms in schizophrenia, this work suggests that there may be significant sex differences in the pathophysiology underlying these symptoms. Elucidating these sex differences may be important for our understanding of the neurobiology of schizophrenia and developing better treatments strategies for the

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

    Science.gov (United States)

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

    2015-06-01

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

  12. Paper Spray and Extraction Spray Mass Spectrometry for the Direct and Simultaneous Quantification of Eight Drugs of Abuse in Whole Blood

    NARCIS (Netherlands)

    Espy, R.D.; Teunissen, S.F.; Manicke, N.E.; Ren, Y.; Ouyang, Z.; van Asten, A.; Cooks, R.G.

    2014-01-01

    Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylene

  13. A public health response to the methamphetamine epidemic: the implementation of contingency management to treat methamphetamine dependence

    Directory of Open Access Journals (Sweden)

    Hare C Bradley

    2006-08-01

    Full Text Available Abstract Background In response to increases in methamphatemine-associated sexually transmitted diseases, the San Francisco Department of Public Health implemented a contingency management (CM field program called the Positive Reinforcement Opportunity Project (PROP. Methods Methamphetamine-using men who have sex with men (MSM in San Francisco qualified for PROP following expressed interest in the program, provision of an observed urine sample that tested positive for methamphetamine metabolites and self-report of recent methamphetamine use. For 12 weeks, PROP participants provided observed urine samples on Mondays, Wednesdays and Fridays and received vouchers of increasing value for each consecutive sample that tested negative to metabolites of methamphetamine. Vouchers were exchanged for goods and services that promoted a healthy lifestyle. No cash was provided. Primary outcomes included acceptability (number of enrollments/time, impact (clinical response to treatment and cost-effectiveness as cost per patient treated. Results Enrollment in PROP was brisk indicating its acceptability. During the first 10 months of operation, 143 men sought treatment and of these 77.6% were HIV-infected. Of those screened, 111 began CM treatment and averaged 15 (42% methamphetamine-free urine samples out of a possible 36 samples during the 12-week treatment period; 60% completed 4 weeks of treatment; 48% 8 weeks and 30% 12 weeks. Across all participants, an average of $159 (SD = $165 in vouchers or 35.1% of the maximum possible ($453 was provided for these participants. The average cost per participant of the 143 treated was $800. Conclusion Clinical responses to CM in PROP were similar to CM delivered in drug treatment programs, supporting the adaptability and effectiveness of CM to non-traditional drug treatment settings. Costs were reasonable and less than or comparable to other methamphetamine outpatient treatment programs. Further expansion of programs

  14. Insanity, methamphetamine and psychiatric expertise in New Zealand courtrooms.

    Science.gov (United States)

    Thom, Katey; Finlayson, Mary; McKenna, Brian

    2011-06-01

    The use of methamphetamine in New Zealand has increased significantly over the last decade. Due to the potential of methamphetamine to induce, exacerbate and precipitate psychotic symptoms, this drug has also taken centre stage in several criminal trials considering the sanity of defendants. Highly publicised and often involving contested expert evidence, these criminal trials have illustrated the limits of using psychiatric expertise to answer legal questions. This article considers the implications of such cases in light of material from a qualitative study that aimed to generate insights into the difficulties forensic psychiatrists and their instructing lawyers face when providing expert evidence on the relationship between methamphetamine, psychosis and insanity. It reports material from 31 in-depth interviews with lawyers and forensic psychiatrists and observation of one criminal trial that considered the relationship between methamphetamine and legal insanity. The findings are correlated with the clinical and medico-legal literature on the topic and subjected to scrutiny through the lens of "sanism". The article concludes that the continued use of forensic psychiatry to meet the legal objectives of insanity, where methamphetamine is involved, has the potential to reinforce sanist attitudes and practices.

  15. Methamphetamine Consumption during Pregnancy - Effects on Child Health.

    Science.gov (United States)

    Dinger, Jürgen; Hinner, Patricia; Reichert, Jörg; Rüdiger, Mario

    2017-02-08

    Methamphetamine abuse during pregnancy represents an emerging health care problem. The consequences are not only of relevance to the pregnant women, but also their unborn child. It is associated with an increased risk of preeclampsia and hypertension, fetal demise, preterm delivery, and intrauterine growth restriction. The deleterious effects of prenatal methamphetamine exposure on the developing fetal brain may lead to long-term neuro-developmental and behavioral problems.Given the current evidence, abuse of methamphetamine during pregnancy must be of utmost concern to health care professionals and to policy-makers. As it has been described for neonatal abstinence syndrome, a multi-professional team is required to improve care of affected women and families. A multi-disciplinary approach is needed, including good prenatal care of pregnant women, perinatal care by specialized obstetricians and neonatologists, and psychiatric treatment by an addiction specialist. Furthermore, families should be integrated into appropriate social support networks.For the development of a structured support program for pregnant women with methamphetamine consumption, methamphetamine use disorder should be considered as a disease that requires medical treatment as well as psychological and social support. The pregnancy should be considered as a window of opportunity to provide the required help.

  16. The Blood-Brain Barrier and Methamphetamine: Open Sesame?

    Directory of Open Access Journals (Sweden)

    Patric eTurowski

    2015-05-01

    Full Text Available The chemical and electrical microenvironment of neurons within the central nervous system is protected and segregated from the circulation by the vascular blood–brain barrier. This barrier operates on the level of endothelial cells and includes regulatory crosstalk with neighbouring pericytes, astrocytes and neurons. Within this neurovascular unit, the endothelial cells form a formidable, highly regulated barrier through the presence of inter-endothelial tight junctions, the absence of fenestrations, and the almost complete absence of fluid-phase transcytosis. The potent psychostimulant drug methamphetamine transiently opens the vascular blood–brain barrier through either or both the modulation of inter-endothelial junctions and the induction of fluid-phase transcytosis. Direct action of methamphetamine on the vascular endothelium induces acute opening of the blood-brain barrier. In addition, striatal effects of methamphetamine and resultant neuroinflammatory signalling can indirectly lead to chronic dysfunction of the blood-brain barrier. Breakdown of the blood-brain barrier may exacerbate the neuronal damage that occurs during methamphetamine abuse. However, this process also constitutes a rare example of agonist-induced breakdown of the blood-brain barrier and the adjunctive use of methamphetamine may present an opportunity to enhance delivery of chemotherapeutic agents to the underlying neural tissue.

  17. Treatment utilization and barriers to treatment: Results of a survey of dependent methamphetamine users

    Directory of Open Access Journals (Sweden)

    Lee Nicole K

    2011-02-01

    Full Text Available Abstract Background Australia has one of the highest rates of methamphetamine use in the world; however, treatment access for methamphetamine is comparatively low. This descriptive study aimed to identify patterns of treatment utilization and perceived barriers to accessing treatment among dependent methamphetamine users in the hope that such information will enable services to more appropriately respond to this group. Methods One hundred and twenty-six methamphetamine users who had a current or past history of methamphetamine dependence were interviewed about their experiences of, and perceived barriers to, treatment. Results Treatment utilization among methamphetamine users was reportedly low. One of the main reasons cited for not accessing treatment was that methamphetamine users did not perceive their drug use to be a problem (despite apparent levels of dependence. Self-detoxification with the use of other licit and illicit drugs was high among this group. Participants identified a lack of confidence in the ability of treatment services to address methamphetamine dependence and the 'opiate-centric' nature of treatment services as significant blocks to treatment entry. Suggestions for improvement by participants included operating specialist services for methamphetamine users, placing an emphasis on responsiveness and routinely involving case management services for this group. Discussion and Conclusions To improve service delivery, treatment services should reorient their services to better address the needs of methamphetamine users by making small changes such as specific opening times for methamphetamine users or using a dedicated space for methamphetamine treatment. Alternative options such as online treatments and specialist methamphetamine clinics should be considered for methamphetamine users.

  18. Role for Rab10 in Methamphetamine-Induced Behavior.

    Directory of Open Access Journals (Sweden)

    Scott M Vanderwerf

    Full Text Available Lipid rafts are specialized, cholesterol-rich membrane compartments that help to organize transmembrane signaling by restricting or promoting interactions with subsets of the cellular proteome. The hypothesis driving this study was that identifying proteins whose relative abundance in rafts is altered by the abused psychostimulant methamphetamine would contribute to fully describing the pathways involved in acute and chronic effects of the drug. Using a detergent-free method for preparing rafts from rat brain striatal membranes, we identified density gradient fractions enriched in the raft protein flotillin but deficient in calnexin and the transferrin receptor, markers of non-raft membranes. Dopamine D1- and D2-like receptor binding activity was highly enriched in the raft fractions, but pretreating rats with methamphetamine (2 mg/kg once or repeatedly for 11 days did not alter the distribution of the receptors. LC-MS analysis of the protein composition of raft fractions from rats treated once with methamphetamine or saline identified methamphetamine-induced changes in the relative abundance of 23 raft proteins, including the monomeric GTP-binding protein Rab10, whose abundance in rafts was decreased 2.1-fold by acute methamphetamine treatment. Decreased raft localization was associated with a selective decrease in the abundance of Rab10 in a membrane fraction that includes synaptic vesicles and endosomes. Inhibiting Rab10 activity by pan-neuronal expression of a dominant-negative Rab10 mutant in Drosophila melanogaster decreased methamphetamine-induced activity and mortality and decreased caffeine-stimulated activity but not mortality, whereas inhibiting Rab10 activity selectively in cholinergic neurons had no effect. These results suggest that activation and redistribution of Rab10 is critical for some of the behavioral effects of psychostimulants.

  19. Applying UML and MDA to Real Systems Design

    CERN Document Server

    Oliver, Ian

    2011-01-01

    Traditionally system design has been made from a black box/functionality only perspective which forces the developer to concentrate on how the functionality can be decomposed and recomposed into so called components. While this technique is well established and well known it does suffer fromsome drawbacks; namely that the systems produced can often be forced into certain, incompatible architectures, difficult to maintain or reuse and the code itself difficult to debug. Now that ideas such as the OMG's Model Based Architecture (MDA) or Model Based Engineering (MBE) and the ubiquitous modelling language UML are being used (allegedly) and desired we face a number of challenges to existing techniques.

  20. Histochemical demonstration of methamphetamine by immunocytochemistry.

    Science.gov (United States)

    Ishiyama, I; Mukaida, M; Yoshii, T; Suyama, H

    1987-05-01

    A method for the demonstration of methamphetamine (MA) by immunocytochemistry was established. The tissues of intoxicated mice, administered various amounts of MA in single doses of from 0.01 to 1 mg of MA-HCl, were fixed in glutaraldehyde-containing fixatives. Cryostat and paraffin slices gave a positive reaction of MA localization by staining the brain, liver, kidney, lung, stomach, spleen, and so forth, with the aid of the indirect immunoperoxidase technique. Those of animals administered a single dose of 0.1 mg or more (over 3 to 4 mg/kg--the usual dose of MA in acute intoxication death in forensic medicine), in particular, gave a strong strong reaction, so that the diagnosis of MA intoxication can be performed by macroscopic observation of stained slices. The histochemical diagnosis of MA intoxication in clinical toxicology and pathology might be regarded as a useful tool, especially in forensic pathology. The following cells gave a strong positive reaction: nerve cells and myelin sheaths, hepatocytes, epithelial cells of the distal part of the renal tubule and of the collecting tubule, alveolar and bronchial epithelial cells of the lung, chief and parietal cells of the gastric gland, capillaries of the renal glomerulus, macrophages in the blood and tissues, and striated muscle cells including cardiocytes. The morphological evidence of the pharmacodynamics and pharmacokinetics of MA can be determined at the cellular level by immunocytochemistry.

  1. Molecular bases of methamphetamine-induced neurodegeneration.

    Science.gov (United States)

    Cadet, Jean Lud; Krasnova, Irina N

    2009-01-01

    Methamphetamine (METH) is a highly addictive psychostimulant drug, whose abuse has reached epidemic proportions worldwide. The addiction to METH is a major public concern because its chronic abuse is associated with serious health complications including deficits in attention, memory, and executive functions in humans. These neuropsychiatric complications might, in part, be related to drug-induced neurotoxic effects, which include damage to dopaminergic and serotonergic terminals, neuronal apoptosis, as well as activated astroglial and microglial cells in the brain. Thus, the purpose of the present paper is to review cellular and molecular mechanisms that might be responsible for METH neurotoxicity. These include oxidative stress, activation of transcription factors, DNA damage, excitotoxicity, blood-brain barrier breakdown, microglial activation, and various apoptotic pathways. Several approaches that allow protection against METH-induced neurotoxic effects are also discussed. Better understanding of the cellular and molecular mechanisms involved in METH toxicity should help to generate modern therapeutic approaches to prevent or attenuate the long-term consequences of psychostimulant use disorders in humans.

  2. 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

  3. Neuropharmacology of New Psychoactive Substances (NPS): Focus on the Rewarding and Reinforcing Properties of Cannabimimetics and Amphetamine-Like Stimulants.

    Science.gov (United States)

    Miliano, Cristina; Serpelloni, Giovanni; Rimondo, Claudia; Mereu, Maddalena; Marti, Matteo; De Luca, Maria Antonietta

    2016-01-01

    New psychoactive substances (NPS) are a heterogeneous and rapidly evolving class of molecules available on the global illicit drug market (e.g smart shops, internet, "dark net") as a substitute for controlled substances. The use of NPS, mainly consumed along with other drugs of abuse and/or alcohol, has resulted in a significantly growing number of mortality and emergency admissions for overdoses, as reported by several poison centers from all over the world. The fact that the number of NPS have more than doubled over the last 10 years, is a critical challenge to governments, the scientific community, and civil society [EMCDDA (European Drug Report), 2014; UNODC, 2014b; Trends and developments]. The chemical structure (phenethylamines, piperazines, cathinones, tryptamines, synthetic cannabinoids) of NPS and their pharmacological and clinical effects (hallucinogenic, anesthetic, dissociative, depressant) help classify them into different categories. In the recent past, 50% of newly identified NPS have been classified as synthetic cannabinoids followed by new phenethylamines (17%) (UNODC, 2014b). Besides peripheral toxicological effects, many NPS seem to have addictive properties. Behavioral, neurochemical, and electrophysiological evidence can help in detecting them. This manuscript will review existing literature about the addictive and rewarding properties of the most popular NPS classes: cannabimimetics (JWH, HU, CP series) and amphetamine-like stimulants (amphetamine, methamphetamine, methcathinone, and MDMA analogs). Moreover, the review will include recent data from our lab which links JWH-018, a CB1 and CB2 agonist more potent than Δ(9)-THC, to other cannabinoids with known abuse potential, and to other classes of abused drugs that increase dopamine signaling in the Nucleus Accumbens (NAc) shell. Thus the neurochemical mechanisms that produce the rewarding properties of JWH-018, which most likely contributes to the greater incidence of dependence associated

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

    Science.gov (United States)

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

    2006-08-01

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

  5. DMPD: MDA5/RIG-I and virus recognition. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18272355 MDA5/RIG-I and virus recognition. Takeuchi O, Akira S. Curr Opin Immunol. ...2008 Feb;20(1):17-22. Epub 2008 Feb 12. (.png) (.svg) (.html) (.csml) Show MDA5/RIG-I and virus recognition.... PubmedID 18272355 Title MDA5/RIG-I and virus recognition. Authors Takeuchi O, Akira S. Publication Curr Opi

  6. File list: Oth.Brs.05.AllAg.MDA-MB-231 [Chip-atlas[Archive

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  7. File list: Unc.Brs.20.AllAg.MDA-MB-231 [Chip-atlas[Archive

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  1. File list: His.Brs.10.AllAg.MDA-MB-231 [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. 5-hydroxytryptamine- and dopamine-releasing effects of ring-substituted amphetamines on rat brain: a comparative study using in vivo microdialysis.

    Science.gov (United States)

    Matsumoto, T; Maeno, Y; Kato, H; Seko-Nakamura, Y; Monma-Ohtaki, J; Ishiba, A; Nagao, M; Aoki, Y

    2014-08-01

    Using in vivo microdialysis, a comparative study was conducted to examine the effects of amphetamine-related compounds (methamphetamine, MAP; 3,4-methylenedioxymethamphetamine, MDMA; p-methoxyamphetamine, PMA; p-methoxymethamphetamine, PMMA; 4-methylthioamphetamine, 4-MTA; 3,4,5-trimethoxyamphetamine, TMA; 2,5-dimethoxy-4-iodoamphetamine, DOI) on extracellular levels of serotonin (5-HT) and dopamine (DA). Dialysates were assayed using HPLC equipped with electrochemical detector following i.p. administration with each drug at a dose of 5 mg/kg. MAP was found to drastically and rapidly increase 5-HT and DA levels (870% and 1460%, respectively). PMA, PMMA, and 4-MTA slightly increased DA levels (150-290%) but remarkably increased 5-HT levels (540-900%). In contrast, TMA and DOI caused no detectable changes in levels of both monoamines. We observed that the potent DA-releasing action of MAP was remarkably decreased by introduction of methoxy or methylthio group at the para position (MAP vs. PMMA or 4-MTA), but introduction of two additional adjacent methoxy groups into PMA totally abolished its 5-HT-/DA-releasing action (PMA vs. TMA). In addition, para-mono-substituted compounds inhibited both monoamine oxidase (MAO) enzymes more strongly than other compounds; PMA and 4-MTA exhibited submicromolar IC50 values for MAO-A. On the other hand, TMA scarcely affected the activity of both MAO enzymes as well as extracellular levels of 5-HT and DA. In this comparative study, MDMA, PMA, and 4-MTA functioned similar to PMMA, a typical empathogen; these findings therefore could be helpful in clarifying the psychopharmacological properties of amphetamine-related, empathogenic designer drugs.

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

    Science.gov (United States)

    Kohl, Randall Lee

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

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

    OpenAIRE

    Natarajan, Reka; Yamamoto, Bryan K.

    2011-01-01

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

  5. Amphetamine Positive Urine Toxicology Screen Secondary to Atomoxetine

    OpenAIRE

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

    2013-01-01

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

  6. Simultaneous qualitative and quantitative method using liquid chromatography selected reaction monitoring-triggered quantitation-enhanced data-dependent tandem mass spectrometry for the identification and classification of amphetamine-type stimulant abusers in human urine.

    Science.gov (United States)

    Lee, Sang Kyu; Kim, So-Hee; Kim, Ho Jun; Yoo, Hye Hyun; Kwon, Oh Seung; In, Moon Kyo; Jin, Changbae; Kim, Dong Hyun; Lee, Jaeick

    2010-11-15

    Amphetamine (AP) and amphetamine-type stimulants, methamphetamine (MA) and N,N-dimethylamphetamine (DMA), are known as central nervous system stimulants, and their abuse throughout the world has recently increased. Since it is difficult to physically distinguish among AP, MA and DMA, analysts may not be aware of what abusers have administered. In this study, following the detection of specific metabolites of AP, MA and DMA as biomarkers in abuser urines, a rapid and sensitive method was developed for the identification and classification of AP-type stimulants abusers. After the simple filtration of the urine samples, the samples were directly analyzed using a liquid chromatography/tandem mass spectrometry system with selected reaction monitoring (SRM)-triggered quantitation-enhanced data-dependent MS/MS (QED-MS/MS) for the simultaneous qualitative and quantitative analysis of p-hydroxy AP, p-hydroxy MA, p-hydroxy DMA, AP, MA, DMA and DMA N-oxide. The determination of p-hydroxy AP, p-hydroxy MA, AP, MA, DMA and DMA N-oxide was accurate and reproducible, with the limits of quantitation of 5 ng/mL in urine. When applied to the urine samples of suspected AP-type stimulants abusers, the abused drugs were precisely identified between MA and DMA abusers.

  7. 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.

  8. 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.

  9. The central amygdala nucleus is critical for incubation of methamphetamine craving.

    Science.gov (United States)

    Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

    2015-04-01

    Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this 'incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4-5 weeks) withdrawal. We first confirmed that 'incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on 'incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving.

  10. A hybrid liquid chromatography-mass spectrometry strategy in a forensic laboratory for opioid, cocaine and amphetamine classes in human urine using a hybrid linear ion trap-triple quadrupole mass spectrometer.

    Science.gov (United States)

    Dowling, Geraldine; Regan, Liam; Tierney, Julie; Nangle, Michael

    2010-10-29

    A rapid method has been developed to analyse morphine, codeine, morphine-3-glucuronide, 6-monoacetylmorphine, cocaine, benzoylegonine, buprenorphine, dihydrocodeine, cocaethylene, 3,4-methylenedioxyamphetamine, ketamine, 3,4-methylenedioxymethamphetamine, pseudoephedrine, lignocaine, benzylpiperazine, methamphetamine, amphetamine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine and methadone in human urine. Urine samples were diluted with methanol:water (1:1, v/v) and sample aliquots were analysed by hybrid linear ion trap-triple quadrupole mass spectrometry with a runtime of 12.5 min. Multiple reaction monitoring (MRM) as survey scan and an enhanced product ion (EPI) scan as dependent scan were performed in an information-dependent acquisition (IDA) experiment. Finally, drug identification and confirmation was carried out by library search with a developed in-house MS/MS library based on EPI spectra at a collision energy spread of 35±15 in positive mode and MRM ratios. The method was validated in urine, according to the criteria defined in Commission Decision 2002/657/EC. At least two MRM transitions for each substance were monitored in addition to EPI spectra and deuterated analytes were used as internal standards for quantitation. The reporting level was 0.05 μg mL(-1) for the range of analytes tested. The regression coefficients (r(2)) for the calibration curves (0-4 μg mL(-1)) in the study were ≥0.98. The method proved to be simple and time efficient and was implemented as an analytical strategy for the illicit drug monitoring of opioids, cocaines and amphetamines in criminal samples from crime offenders, abusers or victims in the Republic of Ireland. To the best of our knowledge there are no hybrid LC-MS applications using MRM mode and product ion spectra in the linear ion trap mode for opioids, cocaines or amphetamines with validation data in urine.

  11. Endoplasmic reticulum stress responses differ in meninges and associated vasculature, striatum, and parietal cortex after a neurotoxic amphetamine exposure.

    Science.gov (United States)

    Thomas, Monzy; George, Nysia I; Saini, Upasana T; Patterson, Tucker A; Hanig, Joseph P; Bowyer, John F

    2010-08-01

    Amphetamine (AMPH) is used to treat attention deficit and hyperactivity disorders, but it can produce neurotoxicity and adverse vascular effects at high doses. The endoplasmic reticulum (ER) stress response (ERSR) entails the unfolded protein response, which helps to avoid or minimize ER dysfunction. ERSR is often associated with toxicities resulting from the accumulation of unfolded or misfolded proteins and has been associated with methamphetamine toxicity in the striatum. The present study evaluates the effect of AMPH on several ERSR elements in meninges and associated vasculature (MAV), parietal cortex, and striatum. Adult, male Sprague-Dawley rats were exposed to saline, environmentally induced hyperthermia (EIH) or four consecutive doses of AMPH that produce hyperthermia. Expression changes (mRNA and protein levels) of key ERSR-related genes in MAV, striatum, and parietal cortex at 3 h or 1 day postdosing were monitored. AMPH increased the expression of some ERSR-related genes in all tissues. Atf4 (activating transcription factor 4, an indicator of Perk pathway activation), Hspa5/Grp78 (Glucose regulated protein 78, master regulator of ERSR), Pdia4 (protein disulfide isomerase, protein-folding enzyme), and Nfkb1 (nuclear factor of kappa b, ERSR sensor) mRNA increased significantly in MAV and parietal cortex 3 h after AMPH. In striatum, Atf4 and Hspa5/Grp78 mRNA significantly increased 3 h after AMPH, but Pdia4 and Nfkb11 did not. Thus, AMPH caused a robust activation of the Perk pathway in all tissues, but significant Ire1 pathway activation occurred only after AMPH treatment in the parietal cortex and striatum. Ddit3/Chop, a downstream effector of the ERSR pathway related to the neurotoxicity, was only increased in striatum and parietal cortex. Conversely, Pdia4, an enzyme protective in the ERSR, was only increased in MAV. The overall ERSR manifestation varied significantly between MAV, striatum, and parietal cortex after a neurotoxic exposure to AMPH.

  12. In-sample derivatization-solid-phase microextraction of amphetamines and ecstasy related stimulants from water and urine.

    Science.gov (United States)

    Racamonde, Inés; Rodil, Rosario; Quintana, José Benito; Cela, Rafael

    2013-04-03

    A solid-phase microextraction (SPME) method for the determination of five amphetamine type stimulants (ATSs) in water and urine samples is presented. Analytes were simultaneously derivatized with iso-butyl chloroformate (iBCF) in the aqueous sample while being extracted, improving in this way the extractability of ATSs and permitting their determination by gas chromatography-mass spectrometry (GC-MS). The SPME procedure was carefully optimized in order to achieve adequate limits of detection (LODs) for environmental concentrations. Hence, different operational parameters were considered: type of SPME coating, ionic strength, basic catalyzer and derivatizing agent amount, extraction time and temperature. The final SPME procedure consists into the extraction of 100mL of sample containing 2 g of dipotassium monohydrogen phosphate trihydrate and 100 μL of iBCF (1:1 in acetonitrile), for 40 min at 60°C with a polydimethylsiloxane-divinylbenzene (PDMS-DVB) fiber. Under these conditions, LODs in wastewater ranged from 0.4 to 2 ng L(-1), relative recoveries in the 84-114% range and relative standard deviations (RSD) lower than 15% were obtained. The application of the method to wastewater and river water samples showed the ecstasy ATS, 3,4-methylenedioxymethamphetamine (MDMA), as the most frequently detected, followed by methamphetamine, in concentrations around 20 ng L(-1). Finally, the method was downscaled and also validated with urine samples, proving its good performance with this matrix too: RSD<11%, recoveries in the 98-110% range and LODs lower than 0.1 μg L(-1).

  13. An agent oriented information system: an MDA based development

    Directory of Open Access Journals (Sweden)

    Mohamed Sadgal

    2012-09-01

    Full Text Available Information systems (IS development should not only accomplish functional models but also conceptual models to represent the organizational environment in which it will have to evolve and must be aligned with strategic objectives. Generally, a significant innovations in the enterprise, is to organize its IS around its business processes. Otherwise, business models must be enriched by the agent paradigm to reduce the complexity involved in solving a problem by the structuring of knowledge on a set of intelligent agents, the association between agents and activities and collaboration among agents. To do this, we propose an agent oriented approach based on the model-driven-architecture (MDA for the information system development. This approach uses in its different phases, the BPMN language for the business processes modeling, AML language for the agent modeling, and JADEX platform for the implementation. The IS development is realized by different automated mappings from source models to target models.

  14. Engineering Runtime Requirements-Monitoring Systems Using MDA Technologies

    Science.gov (United States)

    Skene, James; Emmerich, Wolfgang

    The Model-Driven Architecture (MDA) technology toolset includes a language for describing the structure of meta-data, the MOF, and a language for describing consistency properties that data must exhibit, the OCL. Off-the-shelf tools can generate meta-data repositories and perform consistency checking over the data they contain. In this paper we describe how these tools can be used to implement runtime requirements monitoring of systems by modelling the required behaviour of the system, implementing a meta-data repository to collect system data, and consistency checking the repository to discover violations. We evaluate the approach by implementing a contract checker for the SLAng service-level agreement language, a language defined using a MOF meta-model, and integrating the checker into an Enterprise JavaBeans application. We discuss scalability issues resulting from immaturities in the applied technologies, leading to recommendations for their future development.

  15. MDA based-approach for UML Models Complete Comparison

    CERN Document Server

    Chaouni, Samia Benabdellah; Mouline, Salma

    2011-01-01

    If a modeling task is distributed, it will frequently be necessary to integrate models developed by different team members. Problems occur in the models integration step and particularly, in the comparison phase of the integration. This issue had been discussed in several domains and various models. However, previous approaches have not correctly handled the semantic comparison. In the current paper, we provide a MDA-based approach for models comparison which aims at comparing UML models. We develop an hybrid approach which takes into account syntactic, semantic and structural comparison aspects. For this purpose, we use the domain ontology as well as other resources such as dictionaries. We propose a decision support system which permits the user to validate (or not) correspondences extracted in the comparison phase. For implementation, we propose an extension of the generic correspondence metamodel AMW in order to transform UML models to the correspondence model.

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

    Directory of Open Access Journals (Sweden)

    Rabe-Jabłońska, Jolanta

    2012-08-01

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

  17. Repeated administration of D-amphetamine induces loss of [{sup 123}I]FP-CIT binding to striatal dopamine transporters in rat brain: a validation study

    Energy Technology Data Exchange (ETDEWEB)

    Booij, Jan [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands)]. E-mail: j.booij@amc.uva.nl; Bruin, Kora de [Department of Nuclear Medicine, Academic Medical Center, 1105 AZ Amsterdam (Netherlands); Gunning, W. Boudewijn [Department of Neurology, Epilepsy Centre Kempenhaeghe, 5590 AB Heeze (Netherlands)

    2006-04-15

    In recent years, several PET and SPECT studies have shown loss of striatal dopamine transporter (DAT) binding in amphetamine (AMPH) users. However, the use of DAT SPECT tracers to detect AMPH-induced changes in DAT binding has not been validated. We therefore examined if repeated administration of D-AMPH or methamphetamine (METH) may induce loss of binding to striatal DATs in rats by using an experimental biodistribution study design and a SPECT tracer for the DAT ([{sup 123}I]FP-CIT). Methods: Groups of male rats (n=10 per group) were treated with D-AMPH (10 mg/kg body weight), METH (10 mg/kg body weight), or saline, twice a day for 5 consecutive days. Five days later, [{sup 123}I]FP-CIT was injected intravenously, and 2 h later, the rats were sacrificed and radioactivity was assayed. Results: In D-AMPH but not METH-treated rats, striatal [{sup 123}I]FP-CIT uptake was significantly lower (approximately 17%) than in the control group. Conclusion: These data show that [{sup 123}I]FP-CIT can be used to detect AMPH-induced changes in DAT binding and may validate the use of DAT radiotracers to study AMPH-induced changes in striatal DAT binding in vivo.

  18. 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

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

    NARCIS (Netherlands)

    Bohus, B; de Boer, S.F.

    1990-01-01

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

  20. 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...

  1. 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...

  2. 75 FR 69088 - Determination That Amphetamine Sulfate, 5 and 10 Milligram Tablets, Was Not Withdrawn From Sale...

    Science.gov (United States)

    2010-11-10

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

  3. The Comparison of Attentional Bias and Difficulty of Emotional States Regulation and Their Correlation with Craving Severity in Drug Abuser Methamphetamines and Crack

    Directory of Open Access Journals (Sweden)

    Raheleh Haghiaght

    2014-08-01

    Full Text Available Background: Today, within creased substance, type of substance used has changed. Therefore, drug abuse in population of crack to the stimulant drugs (amphetamine particularly crystal is expanding and increasing. Therefore, the purpose of the present study was the comparison of attentional bias and difficulty of emotional states regulation and their correlation with craving severity in drug abuser methamphetamines and crack. Materials and Methods: Type of research was descriptive analytical correlation. Population was total of users with methamphetamines and crack in summer and fall 2011 at the city of Isfahan, and 34 users with crystal with daily at least one year were selected on the basis of the snow ball sampling and 31 users with crack with daily at least one year were selected on the basis of the sample sampling. The difficulties emotion regulation scale (DERS, Stroop test and OCDUS were used as the outcome measures. For findings used of descriptive statistics and multivariate analysis of covariance (MANCOVA and regression analysis were used. Results: The results of analysis of variance showed that between drug abuser crystal and crack significantly differed of attentional bias and difficulty of emotional states regulation. The greatest differences to components of a lack of transparency, lack of emotional awareness, limit emotional states regulation strategies and of emotional responses. But, only the variable non-acceptance negative emotional of subscale of the difficulty of emotional states regulation was able to craving (as an important indicator of durable use substance in of both crack and crystal predicted. This variable is only 13% of the variance craving in drug abuser crack and crystal can be explained. Other findings showed that although there is no difference between the two groups in the intensity of craving, but attentional bias among drug abuser crack and crystal was a significant difference. Conclusion: Overall, can be said

  4. Altered social cognition in male BDNF heterozygous mice and following chronic methamphetamine exposure.

    Science.gov (United States)

    Manning, Elizabeth E; van den Buuse, Maarten

    2016-05-15

    Growing clinical evidence suggests that persistent psychosis which occurs in methamphetamine users is closely related to schizophrenia. However, preclinical studies in animal models have focussed on psychosis-related behaviours following methamphetamine, and less work has been done to assess endophenotypes relevant to other deficits observed in schizophrenia. Altered social behaviour is a feature of both the negative symptoms and cognitive deficits in schizophrenia, and significantly impacts patient functioning. We recently found that brain-derived neurotrophic factor (BDNF) heterozygous mice show disrupted sensitization to methamphetamine, supporting other work suggesting an important role of this neurotrophin in the pathophysiology of psychosis and the neuronal response to stimulant drugs. In the current study, we assessed social and cognitive behaviours in methamphetamine-treated BDNF heterozygous mice and wildtype littermate controls. Following chronic methamphetamine exposure male wildtype mice showed a 50% reduction in social novelty preference. Vehicle-treated male BDNF heterozygous mice showed a similar impairment in social novelty preference, with a trend for no further disruption by methamphetamine exposure. Female mice were unaffected in this task, and no groups showed any changes in sociability or short-term spatial memory. These findings suggest that chronic methamphetamine alters behaviour relevant to disruption of social cognition in schizophrenia, supporting other studies which demonstrate a close resemblance between persistent methamphetamine psychosis and schizophrenia. Together these findings suggest that dynamic regulation of BDNF signalling is necessary to mediate the effects of methamphetamine on behaviours relevant to schizophrenia.

  5. Modafinil abrogates methamphetamine-induced neuroinflammation and apoptotic effects in the mouse striatum.

    Directory of Open Access Journals (Sweden)

    Mariana Raineri

    Full Text Available Methamphetamine is a drug of abuse that can cause neurotoxic damage in humans and animals. Modafinil, a wake-promoting compound approved for the treatment of sleeping disorders, is being prescribed off label for the treatment of methamphetamine dependence. The aim of the present study was to investigate if modafinil could counteract methamphetamine-induced neuroinflammatory processes, which occur in conjunction with degeneration of dopaminergic terminals in the mouse striatum. We evaluated the effect of a toxic methamphetamine binge in female C57BL/6 mice (4 × 5 mg/kg, i.p., 2 h apart and modafinil co-administration (2 × 90 mg/kg, i.p., 1 h before the first and fourth methamphetamine injections on glial cells (microglia and astroglia. We also evaluated the striatal expression of the pro-apoptotic BAX and anti-apoptotic Bcl-2 proteins, which are known to mediate methamphetamine-induced apoptotic effects. Modafinil by itself did not cause reactive gliosis and counteracted methamphetamine-induced microglial and astroglial activation. Modafinil also counteracted the decrease in tyrosine hydroxylase and dopamine transporter levels and prevented methamphetamine-induced increases in the pro-apoptotic BAX and decreases in the anti-apoptotic Bcl-2 protein expression. Our results indicate that modafinil can interfere with methamphetamine actions and provide protection against dopamine toxicity, cell death, and neuroinflammation in the mouse striatum.

  6. Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced anorexia in mice.

    Science.gov (United States)

    Ginawi, O T; Al-Majed, A A; Al-Suwailem, A K

    2005-03-01

    Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.

  7. Bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone antagonize methamphetamine-induced efflux of dopamine according to their potencies as dopamine uptake inhibitors: implications for the treatment of methamphetamine dependence

    OpenAIRE

    Simmler, Linda D.; Wandeler, Rebecca; Liechti, Matthias E.

    2013-01-01

    Background Methamphetamine-abuse is a worldwide health problem for which no effective therapy is available. Inhibition of methamphetamine-induced transporter-mediated dopamine (DA) release could be a useful approach to treat methamphetamine-addiction. We assessed the potencies of bupropion, methylphenidate, and 3,4-methylenedioxypyrovalerone (MDPV) to block DA uptake or to inhibit methamphetamine-induced DA release in HEK-293 cells expressing the human DA transporter. Findings Bupropion, meth...

  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. Direct Injection LC-MS-MS Analysis of Opiates, Methamphetamine, Buprenorphine, Methadone and Their Metabolites in Oral Fluid from Substitution Therapy Patients.

    Science.gov (United States)

    Liu, Hsiu-Chuan; Lee, Hsi-Tzu; Hsu, Ya-Ching; Huang, Mei-Han; Liu, Ray H; Chen, Tai-Jui; Lin, Dong-Liang

    2015-01-01

    A rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed, validated and applied to simultaneous analysis of oral fluid samples for the following 10 analytes: methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, norbuprenorphine, morphine, codeine, 6-acetylmorphine, 6-acetylcodeine, amphetamine, and methamphetamine. The oral fluid sample was briefly centrifuged and the supernatant was directly injected into the LC-MS-MS system operated under reverse-phase chromatography and electrospray ionization (ESI). Deuterated analogs of the analytes were adopted as the internal standards and found to be effective (except for buprenorphine) to compensate for potential matrix effects. Each analytical run took 0.99) established for buprenorphine and the other nine analytes were 5-100 and 1-100 ng/mL. Intra- and interday precision (% CV) ranges for the 10 analytes were 0.87-12.2% and 1.27-12.8%, while the corresponding accuracy (%) ranges were 91.8-113% and 91.9-111%. Limits of detection and quantitation established for these 10 analytes were in the ranges of 0.1-1.0 and 0.25-1.0 ng/mL (5 ng/mL for buprenorphine). The method was successfully applied to the analysis of 62 oral fluid specimens collected from patients participating in methadone and buprenorphine substitution therapy programs. Analytical results of methadone and buprenorphine were compared with data derived from GC-MS analysis and found to be compatible. Overall, the direct injection LC-MS-MS method performed well, permitting rapid analysis of oral fluid samples for simultaneous quantification of methadone, buprenorphine, opiate and amphetamine drug categories without extensive sample preparation steps.

  10. Enhanced upregulation of CRH mRNA expression in the nucleus accumbens of male rats after a second injection of methamphetamine given thirty days later.

    Directory of Open Access Journals (Sweden)

    Jean Lud Cadet

    Full Text Available Methamphetamine (METH is a widely abused amphetamine analog. Few studies have investigated the molecular effects of METH exposure in adult animals. Herein, we determined the consequences of an injection of METH (10 mg/kg on transcriptional effects of a second METH (2.5 mg/kg injection given one month later. We thus measured gene expression by microarray analyses in the nucleus accumbens (NAc of 4 groups of rats euthanized 2 hours after the second injection: saline-pretreated followed by saline-challenged (SS or METH-challenged (SM; and METH-pretreated followed by saline-challenged (MS or METH-challenged (MM. Microarray analyses revealed that METH (2.5 mg/kg produced acute changes (1.8-fold; P<0.01 in the expression of 412 (352 upregulated, 60 down-regulated transcripts including cocaine and amphetamine regulated transcript, corticotropin-releasing hormone (Crh, oxytocin (Oxt, and vasopressin (Avp that were upregulated. Injection of METH (10 mg/kg altered the expression of 503 (338 upregulated, 165 down-regulated transcripts measured one month later (MS group. These genes also included Cart and Crh. The MM group showed altered expression of 766 (565 upregulated, 201 down-regulated transcripts including Avp, Cart, and Crh. The METH-induced increased Crh expression was enhanced in the MM group in comparison to SM and MS groups. Quantitative PCR confirmed the METH-induced changes in mRNA levels. Therefore, a single injection of METH produced long-lasting changes in gene expression in the rodent NAc. The long-term increases in Crh, Cart, and Avp mRNA expression suggest that METH exposure produced prolonged activation of the endogenous stress system. The METH-induced changes in oxytocin expression also suggest the possibility that this neuropeptide might play a significant role in the neuroplastic and affiliative effects of this drug.

  11. Integrating Software Architecture Concepts into the MDA Platform with UML Profile

    Directory of Open Access Journals (Sweden)

    Adel Alti

    2007-01-01

    Full Text Available Architecture Description Languages (ADLs provide an abstract representation of software systems. Achieving a concrete mapping of such representation into the implementation is one of the principal aspects of MDA (Model Driven Architecture. Integration of ADLs within MDA confers to the MDA platform a higher level of abstraction and a degree of reuse of ADLs. Indeed they have significantly different platform metamodels which make the definition of mapping rules complex. This complexity is clearly noticeable when some software architecture concepts cannot be easily mapped to MDA platform. In this research, we propose to integrate software architecture within MDA. We define also strategy for direct transformation using a UML profile. It represents both software architecture model (PIM and MDA platform model (PSM in UML meta-model then elaborates transformation rules between results UML meta-models. The goal is to automate the process of deriving implementation platform from software concepts.

  12. Adenovirus vector expressing mda-7 selectively kills hepatocellular carcinoma cell line Hep3B

    Institute of Scientific and Technical Information of China (English)

    Xin-Bo Xue; Kun Chen; Cong-Jun Wang; Jian-Wei Zheng; Yuan Yu; Zhi-Hai Peng; Zai-De Wu

    2008-01-01

    BACKGROUND: Melanoma differentiation associated gene-7 (mda-7) is a novel tumor suppressor gene, which has suppressor activity in a broad spectrum of human cancer cells both in vitro and in vivo through activation of various intracellular signaling pathways. In this study, we investigated the potential effect of mda-7 on human hepatocellular carcinoma (HCC) in vitro. METHODS: Cells from the human HCC cell line Hep3B and the human liver cell line L-02 were assigned to three groups. One was cultured in Dulbecco's modiifed Eagle's medium without serum (control). The others were transfected with adenovirus expressing the mda-7 gene (Ad.mda-7) or adenovirus vector serving as negative control (Ad.vec). The expression of MDA-7 and Bcl-2 proteins in Hep3B and L-02 cells was conifrmed by the reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay. The methyl thiazolyl tetrazolium colorimetric assay and lfow cytometry were used to assess tumor cell proliferation and the cell cycle. Hoechst and Annexin-V/propidium iodide staining were used to study mda-7 gene expression in Hep3B and L-02 cells. The expression of MDA-7, Bcl-2 and Bax proteins were detected by Western blotting. RESULTS: The mda-7 gene was expressed in Hep3B and L-02 cells. The protein concentrations of MDA-7 in supernatants were 790 and 810 pg/ml, respectively. mda-7 induced Hep3B growth suppression and apoptosis, compared with Ad.mda-7 and control (P CONCLUSIONS: mda-7 selectively induces growth inhibi-tion and apoptosis in the HCC cell line Hep3B but not in the normal liver cell line L-02 via downregulating the anti-apoptosis protein Bcl-2. It could be an ideal gene for gene therapy in HCC.

  13. Effects of Environmental Manipulations and Treatment with Bupropion and Risperidone on Choice between Methamphetamine and Food in Rhesus Monkeys.

    Science.gov (United States)

    Banks, Matthew L; Blough, Bruce E

    2015-08-01

    Preclinical and human laboratory choice procedures have been invaluable in improving our knowledge of the neurobiological mechanisms of drug reinforcement and in the drug development process for candidate medications to treat drug addiction. However, little is known about the neuropharmacological mechanisms of methamphetamine vs food choice. The aims of this study were to develop a methamphetamine vs food choice procedure and determine treatment effects with two clinically relevant compounds: the monoamine uptake inhibitor bupropion and the dopamine antagonist risperidone. Rhesus monkeys (n=6) responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and intravenous methamphetamine injections (0-0.32 mg/kg/injection, FR10 schedule) during 7-day bupropion (0.32-1.8 mg/kg/h) and risperidone (0.001-0.0056 mg/kg/h) treatment periods. For comparison, effects of removing food pellets or methamphetamine injections and FR response requirement manipulations were also examined. Under saline treatment conditions, food was preferred over no methamphetamine or small unit methamphetamine doses (0.01-0.032 mg/kg/injection). Larger methamphetamine doses resulted in greater methamphetamine preference and 0.32 mg/kg/injection methamphetamine maintained near exclusive preference. Removing food availability increased methamphetamine choice, whereas removing methamphetamine availability decreased methamphetamine choice. Methamphetamine choice was not significantly altered when the FR response requirements for food and drug were the same (FR100:FR100 or FR10:FR10). Risperidone treatment increased methamphetamine choice, whereas bupropion treatment did not alter methamphetamine choice up to doses that decreased rates of operant behavior. Overall, these negative results with bupropion and risperidone are concordant with previous human laboratory and clinical trials and support the potential validity of this preclinical methamphetamine vs food

  14. Tumour suppressor function of MDA-7/IL-24 in human breast cancer

    Directory of Open Access Journals (Sweden)

    Patani Neill

    2010-08-01

    Full Text Available Abstract Introduction Melanoma differentiation associated gene-7 (MDA-7, also known as interleukin (IL-24, is a tumour suppressor gene associated with differentiation, growth and apoptosis. However, the mechanisms underlying its anti-neoplastic activity, tumour-specificity and efficacy across a spectrum of human cancers have yet to be fully elucidated. In this study, the biological impact of MDA-7 on the behavior of breast cancer (BC cells is evaluated. Furthermore, mRNA expression of MDA-7 is assessed in a cohort of women with BC and correlated with established pathological parameters and clinical outcome. Methods The human BC cell line MDA MB-231 was used to evaluate the in-vitro impact of recombinant human (rh-MDA-7 on cell growth and motility, using a growth assay, wounding assay and electric cell impedance sensing (ECIS. Localisation of MDA-7 in mammary tissues was assessed with standard immuno-histochemical methodology. BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, MDA-7 transcript levels were determined using real-time quantitative PCR. Transcript levels were analyzed against tumour size, grade, oestrogen receptor (ER status, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Exposure to rh-MDA-7 significantly reduced wound closure rates for human BC cells in-vitro. The ECIS model demonstrated a significantly reduced motility and migration following rh-MDA-7 treatment (p = 0.024. Exposure to rh-MDA-7 was only found to exert a marginal effect on growth. Immuno-histochemical staining of human breast tissues revealed substantially greater MDA-7 positivity in normal compared to cancer cells. Significantly lower MDA-7 transcript levels were identified in those predicted to have a poorer prognosis by the NPI (p = 0.049 and those with node positive tumours. Significantly lower expression was also noted in tumours from

  15. Duration of Shh signaling contributes to mDA neuron diversity

    OpenAIRE

    Hayes, Lindsay; Ralls, Sherry; Wang, Hui; Ahn, Sohyun

    2012-01-01

    Sonic hedgehog (Shh) signaling is critical for various developmental processes including specification of the midbrain dopamine (mDA) neurons in the ventral mesencephalon (vMes). While the timing of Shh and its response gene Gli1 segregates mDA neurons, their overall lineage contribution to mDA neurons heavily overlaps. Here, we demonstrate that the same set of mDA neuron progenitors sequentially respond to Shh signaling (Gli1 expression), induce Shh expression, and then turn off Shh responsi...

  16. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications

    Energy Technology Data Exchange (ETDEWEB)

    Volkow, N.D.; Fowler, J.; Volkow, N.D.; Fowler, J.S.; Wang, G.-J.; Shumay, E.; Telang, F.; Thanos, P.; Alexoff, D.

    2010-12-01

    Methamphetamine is one of the most toxic of the drugs of abuse, which may reflect its distribution and accumulation in the body. However no studies have measured methamphetamine's organ distribution in the human body. Positron Emission Tomography (PET) was used in conjunction with [{sup 11}C]d-methamphetamine to measure its whole-body distribution and bioavailability as assessed by peak uptake (% Dose/cc), rate of clearance (time to reach 50% peak-clearance) and accumulation (area under the curve) in healthy participants (9 Caucasians and 10 African Americans). Methamphetamine distributed through most organs. Highest uptake (whole organ) occurred in lungs (22% Dose; weight {approx}1246 g), liver (23%; weight {approx}1677 g) and intermediate in brain (10%; weight {approx}1600 g). Kidneys also showed high uptake (per/cc basis) (7%; weight 305 g). Methamphetamine's clearance was fastest in heart and lungs (7-16 minutes), slowest in brain, liver and stomach (>75 minutes), and intermediate in kidneys, spleen and pancreas (22-50 minutes). Lung accumulation of [{sup 11}C]d-methamphetamine was 30% higher for African Americans than Caucasians (p < 0.05) but did not differ in other organs. The high accumulation of methamphetamine, a potent stimulant drug, in most body organs is likely to contribute to the medical complications associated with methamphetamine abuse. In particular, we speculate that methamphetamine's high pulmonary uptake could render this organ vulnerable to infections (tuberculosis) and pathology (pulmonary hypertension). Our preliminary findings of a higher lung accumulation of methamphetamine in African Americans than Caucasians merits further investigation and questions whether it could contribute to the infrequent use of methamphetamine among African Americans.

  17. Partial MHC/neuroantigen peptide constructs: a potential neuroimmune-based treatment for methamphetamine addiction.

    Directory of Open Access Journals (Sweden)

    Jennifer M Loftis

    Full Text Available Relapse rates following current methamphetamine abuse treatments are very high (∼40-60%, and the neuropsychiatric impairments (e.g., cognitive deficits, mood disorders that arise and persist during remission from methamphetamine addiction likely contribute to these high relapse rates. Pharmacotherapeutic development of medications to treat addiction has focused on neurotransmitter systems with only limited success, and there are no Food and Drug Administration approved pharmacotherapies for methamphetamine addiction. A growing literature shows that methamphetamine alters peripheral and central immune functions and that immune factors such as cytokines, chemokines, and adhesion molecules play a role in the development and persistence of methamphetamine induced neuronal injury and neuropsychiatric impairments. The objective of this study was to evaluate the efficacy of a new immunotherapy, partial MHC/neuroantigen peptide construct (RTL551; pI-A(b/mMOG-35-55, in treating learning and memory impairments induced by repeated methamphetamine exposure. C57BL/6J mice were exposed to two different methamphetamine treatment regimens (using repeated doses of 4 mg/kg or 10 mg/kg, s.c.. Cognitive performance was assessed using the Morris water maze and CNS cytokine levels were measured by multiplex assay. Immunotherapy with RTL551 improved the memory impairments induced by repeated methamphetamine exposure in both mouse models of chronic methamphetamine addiction. Treatment with RTL551 also attenuated the methamphetamine induced increases in hypothalamic interleukin-2 (IL-2 levels. Collectively, these initial results indicate that neuroimmune targeted therapies, and specifically RTL551, may have potential as treatments for methamphetamine-induced neuropsychiatric impairments.

  18. The Infant Development, Environment, and Lifestyle Study: Effects of Prenatal Methamphetamine Exposure, Polydrug Exposure, and Poverty on Intrauterine Growth

    Science.gov (United States)

    Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Liu, Jing; Lester, Barry M.

    2007-01-01

    Objective: Methamphetamine use among pregnant women is an increasing problem in the United States. Effects of methamphetamine use during pregnancy on fetal growth have not been reported in large, prospective studies. We examined the neonatal growth effects of prenatal methamphetamine exposure in the multicenter, longitudinal Infant Development,…

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

    Science.gov (United States)

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

    2011-04-01

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

  20. Hnrnph1 Is A Quantitative Trait Gene for Methamphetamine Sensitivity.

    Directory of Open Access Journals (Sweden)

    Neema Yazdani

    2015-12-01

    Full Text Available Psychostimulant addiction is a heritable substance use disorder; however its genetic basis is almost entirely unknown. Quantitative trait locus (QTL mapping in mice offers a complementary approach to human genome-wide association studies and can facilitate environment control, statistical power, novel gene discovery, and neurobiological mechanisms. We used interval-specific congenic mouse lines carrying various segments of chromosome 11 from the DBA/2J strain on an isogenic C57BL/6J background to positionally clone a 206 kb QTL (50,185,512-50,391,845 bp that was causally associated with a reduction in the locomotor stimulant response to methamphetamine (2 mg/kg, i.p.; DBA/2J < C57BL/6J-a non-contingent, drug-induced behavior that is associated with stimulation of the dopaminergic reward circuitry. This chromosomal region contained only two protein coding genes-heterogeneous nuclear ribonucleoprotein, H1 (Hnrnph1 and RUN and FYVE domain-containing 1 (Rufy1. Transcriptome analysis via mRNA sequencing in the striatum implicated a neurobiological mechanism involving a reduction in mesolimbic innervation and striatal neurotransmission. For instance, Nr4a2 (nuclear receptor subfamily 4, group A, member 2, a transcription factor crucial for midbrain dopaminergic neuron development, exhibited a 2.1-fold decrease in expression (DBA/2J < C57BL/6J; p 4.2 x 10-15. Transcription activator-like effector nucleases (TALENs-mediated introduction of frameshift deletions in the first coding exon of Hnrnph1, but not Rufy1, recapitulated the reduced methamphetamine behavioral response, thus identifying Hnrnph1 as a quantitative trait gene for methamphetamine sensitivity. These results define a novel contribution of Hnrnph1 to neurobehavioral dysfunction associated with dopaminergic neurotransmission. These findings could have implications for understanding the genetic basis of methamphetamine addiction in humans and the development of novel therapeutics for

  1. Glial Reactivity in Resistance to Methamphetamine-Induced Neurotoxicity

    OpenAIRE

    Friend, Danielle M.; Keefe, Kristen A

    2013-01-01

    Neurotoxic regimens of methamphetamine (METH) result in reactive microglia and astrocytes in striatum. Prior data indicate that rats with partial dopamine (DA) loss resulting from prior exposure to METH are resistant to further decreases in striatal DA when re-exposed to METH 30 days later. Such resistant animals also do not show an activated microglia phenotype, suggesting a relation between microglial activation and METH-induced neurotoxicity. To date, the astrocyte response in such resista...

  2. Methamphetamine and MDMA: ‘Safe’ drugs of abuse

    Directory of Open Access Journals (Sweden)

    Allana M. Krolikowski

    2014-03-01

    Full Text Available Methamphetamine and MDMA have been called safe drugs of abuse. Worldwide there is an increased consumption of these drugs, which has become a focus of research in South Africa. As the number of methamphetamine users has increased in many African countries, it is essential that emergency care practitioners are able to diagnose and manage intoxication with methamphetamine, MDMA, and other derivatives. The most common presentations include restlessness, agitation, hypertension, tachycardia, and headache while hyperthermia, hyponatraemia, and rhabdomyolysis are among the most common serious complications. Most deaths are secondary to hyperthermia complicated by multiple organ failure. A number of laboratory analyses should be obtained if locally available. We provide a review of the current recommended general and specific management approaches. Benzodiazepines are the first line therapy for hyperthermia, agitation, critical hypertension, and seizures. Patients with serious complications are best managed in an intensive care unit if available. Emergency centres should create protocols and/or further train staff in the recognition and management of intoxication with these ‘not so safe’ drugs.

  3. Extinction of drug cue reactivity in methamphetamine-dependent individuals.

    Science.gov (United States)

    Price, Kimber L; Saladin, Michael E; Baker, Nathaniel L; Tolliver, Bryan K; DeSantis, Stacia M; McRae-Clark, Aimee L; Brady, Kathleen T

    2010-09-01

    Conditioned responses to drug-related environmental cues (such as craving) play a critical role in relapse to drug use. Animal models demonstrate that repeated exposure to drug-associated cues in the absence of drug administration leads to the extinction of conditioned responses, but the few existing clinical trials focused on extinction of conditioned responses to drug-related cues in drug-dependent individuals show equivocal results. The current study examined drug-related cue reactivity and response extinction in a laboratory setting in methamphetamine-dependent individuals. Methamphetamine cue-elicited craving was extinguished during two sessions of repeated (3) within-session exposures to multi-modal (picture, video, and in-vivo) cues, with no evidence of spontaneous recovery between sessions. A trend was noted for a greater attenuation of response in participants with longer (4-7 day) inter-session intervals. These results indicate that extinction of drug cue conditioned responding occurs in methamphetamine-dependent individuals, offering promise for the development of extinction- based treatment strategies.

  4. Escalating dose pretreatment induces pharmacodynamic and not pharmacokinetic tolerance to a subsequent high-dose methamphetamine binge.

    Science.gov (United States)

    O'Neil, Meghan L; Kuczenski, Ronald; Segal, David S; Cho, Arthur K; Lacan, Goran; Melega, William P

    2006-11-01

    A major feature of human methamphetamine (METH) abuse is the gradual dose escalation that precedes high-dose exposure. The period of escalating doses (EDs) is likely associated with development of tolerance to aspects of METH's pharmacologic and toxic effects but the relative contributions of pharmacokinetic and pharmacodynamic factors have not been well defined. In our prior studies in rats, we showed that pretreatment with an ED-METH regimen (0.1-4.0 mg/kg over 14 days) attenuated the toxicity of a subsequently administered high-dose METH binge (4 x 6 mg/kg at 2 h interval) that itself produced behavioral stereotypy, increases in core temperature, and decreases in DA system phenotypic markers in caudate-putamen (CP). Using those ED-METH and binge protocols in the present studies, pharmacokinetic and pharmacodynamic parameters that may have contributed to the apparent neuroprotection afforded by ED-METH were assessed. The ED-METH regimen itself reduced [(3)H]WIN35,428 (WIN) binding to the dopamine transporter (DAT) by 15% in CP, but did not affect DA content. During the METH binge, ED-METH pretreated animals showed attenuated increases in core temperature while concurrent microdialysis studies in CP showed a reduced DA response despite unaltered extracellular levels of METH. At 1 h after the binge, concentrations of METH and its metabolite amphetamine in brain and plasma were unaffected by the ED-METH. The results show that ED-METH pretreatment produces reductions in DAT binding and the DA response during a subsequent METH binge by altering pharmacodynamic and not pharmacokinetic parameters.

  5. Demand for Substance Abuse Treatment Related to Use of Crystal Methamphetamine in Ontario: An Observational Study

    Science.gov (United States)

    Brands, Bruna; Corea, Larry; Strike, Carol; Singh, Veeran-Anne S.; Behrooz, Renee C.; Rush, Brian

    2012-01-01

    Concerns about methamphetamine/crystal methamphetamine (MA) have featured prominently in the Canadian media and on addiction treatment agency agendas. We examined MA admissions at addiction treatment agencies to determine if a service gap existed. In 2006, all addiction treatment agencies (n = 124) in Ontario, Canada were invited to complete an…

  6. Chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine.

    Science.gov (United States)

    Koriem, Khaled M M; Soliman, Rowan E

    2014-01-01

    Methamphetamine intoxication can cause acute hepatic failure. Chlorogenic and caftaric acids are the major dietary polyphenols present in various foods. The aim of this study was to evaluate the protective role of chlorogenic and caftaric acids in liver toxicity and oxidative stress induced by methamphetamine in rats. Thirty-two male albino rats were divided into 4 equal groups. Group 1, which was control group, was injected (i.p) with saline (1 mL/kg) twice a day over seven-day period. Groups 2, 3, and 4 were injected (i.p) with methamphetamine (10 mg/kg) twice a day over seven-day period, where groups 3 and 4 were injected (i.p) with 60 mg/kg chlorogenic acid and 40 mg/kg caftaric acid, respectively, one day before methamphetamine injections. Methamphetamine increased serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, cholesterol, low-density lipoprotein, and triglycerides. Also, malondialdehyde in serum, liver, and brain and plasma and liver nitric oxide levels were increased while methamphetamine induced a significant decrease in serum total protein, albumin, globulin, albumin/globulin ratio, brain serotonin, norepinephrine and dopamine, blood and liver superoxide dismutase, and glutathione peroxidase levels. Chlorogenic and caftaric acids prior to methamphetamine injections restored all the above parameters to normal values. In conclusion, chlorogenic and caftaric acids before methamphetamine injections prevented liver toxicity and oxidative stress where chlorogenic acid was more effective.

  7. Simple HPLC method for detection of trace ephedrine and pseudoephedrine in high-purity methamphetamine.

    Science.gov (United States)

    Makino, Yukiko

    2012-03-01

    A simple and sensitive HPLC technique was developed for the qualitative determination of ephedrine and pseudoephedrine (ephedrines), used as precursors of clandestine d-methamphetamine hydrochloride of high purity. Good separation of ephedrines from bulk d-methamphetamine was achieved, without any extraction or derivatization procedure on a CAPCELLPACK C18 MGII (250 × 4.6 mm) column. The mobile phase consisted of 50 mM KH2 PO4-acetonitrile (94:6 v/v %) using an isocratic pump system within 20 min for detecting two analytes. One run took about 50 min as it was necessary to wash out overloaded methamphetamine for column conditioning. The analytes were detected by UV absorbance measurement at 210 nm. A sample (20 mg) was simply dissolved in 1 mL of water, and a 50 μL aliquot of the solution was injected into the HPLC. The detection limits for ephedrine and pseudoephedrine in bulk d-methamphetamine were as low as 3 ppm each. This analytical separation technique made it possible to detect ephedrine and/or pseudoephedrine in seven samples of high-purity d-methamphetamine hydrochloride seized in Japan. The presence of trace ephedrines in illicit methamphetamine may strongly indicate a synthetic route via ephedrine in methamphetamine profiling. This method is simple and sensitive, requiring only commonly available equipment, and should be useful for high-purity methamphetamine profiling.

  8. Methamphetamine Use among Rural White and Native American Adolescents: An Application of the Stress Process Model

    Science.gov (United States)

    Eitle, David J.; Eitle, Tamela McNulty

    2013-01-01

    Methamphetamine use has been identified as having significant adverse health consequences, yet we know little about the correlates of its use. Additionally, research has found that Native Americans are at the highest risk for methamphetamine use. Our exploratory study, informed by the stress process model, examines stress and stress buffering…

  9. A Creative Partnership: The Spiritual and the Sexual in Novels by Zakes Mda

    NARCIS (Netherlands)

    Visser, I.

    2012-01-01

    Spirituality and sexuality are key notions in the novels of Zakes Mda, one of South Africa's leading contemporary authors. In Mda's novels the mysterious interrelatedness of the spiritual and the sexual, in which art and creativity are vital elements, functions as a catalyst in individual and collec

  10. Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts

    DEFF Research Database (Denmark)

    Gonen, Ayelet; Hansen, Lotte; Turner, William W

    2014-01-01

    Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use as a...

  11. Digital Droplet Multiple Displacement Amplification (ddMDA for Whole Genome Sequencing of Limited DNA Samples.

    Directory of Open Access Journals (Sweden)

    Minsoung Rhee

    Full Text Available Multiple displacement amplification (MDA is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently, the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet, ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.

  12. An MDA-based approach for behaviour modelling of context-aware mobile applications

    NARCIS (Netherlands)

    Daniele, Laura M.; Ferreira Pires, Luis; Sinderen, van Marten

    2009-01-01

    Most reported MDA approaches give much attention to structural aspects in PSMs and in generated code, and less attention to the PIM level and the behaviour of the modelled applications. Consequently, application behaviour is generally not (well) defined at the PIM level. This paper presents an MDA-b

  13. Cardiovascular effects of methamphetamine in dogs treated chronically with the amine.

    Science.gov (United States)

    Vidrio, H

    1982-01-01

    Methamphetamine is one of a group of sympathomimetic amines that lower blood pressure upon chronic administration to hypertensive dogs. To determine whether tolerance to the cardiovascular effects of these drugs could play a role in their antihypertensive action, acute blood pressure responses to oral d-methamphetamine were determined in trained conscious renal hypertensive dogs at weekly intervals during treatment with the drug for 2 months. Responses were also obtained in similarly treated normotensive dogs and in normotensive and hypertensive animals receiving l-methamphetamine. Pressor responses to d-methamphetamine in hypertensive dogs remained unchanged throughout treatment, while in all other cases they diminished gradually. Only the dextro isomer reduced blood pressure chronically in the hypertensive group. It was concluded that tolerance is not involved in the antihypertensive effect of methamphetamine and that, considering the stereo specificity of this effect, residual lowering of blood pressure might involve formation of a false mediator metabolite of the amine.

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

    Science.gov (United States)

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

    2014-03-01

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

  15. Profiles of urine samples taken from Ecstasy users at Rave parties: analysis by immunoassays, HPLC, and GC-MS.

    Science.gov (United States)

    Zhao, H; Brenneisen, R; Scholer, A; McNally, A J; ElSohly, M A; Murphy, T P; Salamone, S J

    2001-01-01

    The abuse of the designer amphetamines such as 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is increasing throughout the world. They have become popular drugs, especially at all-night techno dance parties (Raves), and their detection is becoming an important issue. Presently, there are no MDMA- or MDA-specific immunoassays on the market, and detection of the designer amphetamines is dependent upon the use of commercially available amphetamine assays. The success of this approach has been difficult to assess because of the general unavailability of significant numbers of samples from known drug users. The objectives of the present study are to characterize the drug content of urine samples from admitted Ecstasy users by chromatographic methods and to assess the ability of the available amphetamine/methamphetamine immunoassays to detect methylenedioxyamphetamines. We found that, when analyzed by high-performance liquid chromatography with diode-array detection (HPLC-DAD), 64% of 70 urine samples (by gas chromatography-mass spectrometry [GC-MS]: 88% of 64 urine samples) obtained from Rave attendees contained MDMA and/or 3,4-methylenedioxyamphetamine (MDA) alone or in combination with amphetamine, methamphetamine, or other designer amphetamines such as 3,4-methylenedioxyethylamphetamine (MDEA). This suggests that the majority of the Ravers are multidrug users. At the manufacturer's suggested cutoffs, the Abbott TDx Amphetamine/Methamphetamine II and the new Roche HS Amphetamine/MDMA assays demonstrated greater detection sensitivity for MDMA than the other amphetamine immunoassays tested (Abuscreen OnLine Hitachi AMPS, Abuscreen OnLine Integra AMPS, Abuscreen OnLine Integra AMPSX, CEDIA AMPS, and EMIT II AMPS). There is 100% agreement between each of the two immunoassays with the reference chromatographic methods, HPLC-DAD and GC-MS, for the detection of methylenedioxyamphetamines.

  16. "Nothing Is Free": A Qualitative Study of Sex Trading Among Methamphetamine Users in Cape Town, South Africa.

    Science.gov (United States)

    Watt, Melissa H; Kimani, Stephen M; Skinner, Donald; Meade, Christina S

    2016-05-01

    South Africa is facing an established epidemic of methamphetamine, known locally as "tik." Globally, methamphetamine has been linked to high rates of sexual risk behaviors, including sex trading. The goal of this study was to qualitatively examine the experiences of sex trading among methamphetamine users in Cape Town, South Africa. Individual in-depth interviews were conducted with 30 active methamphetamine users (17 men and 13 women) recruited from the community. Interviews were conducted in local languages using a semi-structured guide that included questions on sex trading experiences and perceptions of sex trading among methamphetamine users. Interviews were audio-recorded, transcribed, and analyzed using analytic memos and coding with constant comparison techniques. The data revealed that in a setting of high levels of addiction and poverty, sex was an important commodity for acquiring methamphetamine. Women were more likely to use sex to acquire methamphetamine, but men reported opportunistic cases of trading sex for methamphetamine. Four models of sex trading emerged: negotiated exchange, implicit exchange, relationships based on resources, and facilitating sex exchange for others. The expectation of sex trading created a context in which sexual violence against female methamphetamine users was common. Multiple sexual partners and inconsistent condom use in acts of sex trading put methamphetamine users at high risk of HIV. Interventions in this setting should address addiction, which is the primary driver of sex trading among methamphetamine users. Harm reduction interventions may include education about HIV and other sexually transmitted infections, availability of condoms and HIV testing, and sexual violence prevention.

  17. Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.

    Directory of Open Access Journals (Sweden)

    Jean Lud Cadet

    Full Text Available Methamphetamine (METH is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge. Quantitative PCR confirmed METH-induced changes in genes of interest and identified additional genes that were differentially impacted by the toxic METH challenge in the presence of METH preconditioning. These genes include small heat shock 27 kD 27 protein 2 (HspB2, thyrotropin-releasing hormone (TRH, brain derived neurotrophic factor (BDNF, c-fos, and some encoding antioxidant proteins including CuZn superoxide dismutase (CuZnSOD, glutathione peroxidase (GPx-1, and heme oxygenase-1 (Hmox-1. These observations are consistent, in part, with the transcriptional alterations reported in models of lethal ischemic injuries which are preceded by ischemic or pharmacological preconditioning. Our findings suggest that multiple molecular pathways might work in tandem to protect the nigrostriatal dopaminergic pathway against the deleterious effects of the toxic psychostimulant. Further analysis of the molecular and cellular pathways regulated by these genes should help to

  18. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  19. PI3K signaling supports amphetamine-induced dopamine efflux.

    Science.gov (United States)

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

    2008-08-01

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

  20. Experimental Investigation on Terahertz Spectra of Amphetamine Type Stimulants

    Science.gov (United States)

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

    2005-12-01

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

  1. The shapes of neurotransmitters by millimetrewave spectroscopy: amphetamine

    Science.gov (United States)

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

    2001-12-01

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

  2. In vivo amphetamine action is contingent on αCaMKII

    DEFF Research Database (Denmark)

    Steinkellner, Thomas; Mus, Liudmilla; Eisenrauch, Birgit

    2014-01-01

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

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

    Science.gov (United States)

    Arnold, L. Eugene; And Others

    1978-01-01

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

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2009-08-01

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

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

    Science.gov (United States)

    Ko, Françoise; Tallerico, Teresa; Seeman, Philip

    2006-08-01

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

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

    Science.gov (United States)

    Faraone, Stephen V

    2007-09-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  9. At the borders, on the edge: use of injected methamphetamine in Tijuana and Ciudad Juarez, Mexico.

    Science.gov (United States)

    Case, Patricia; Patricia, Case; Ramos, Rebeca; Brouwer, Kimberly C; Firestone-Cruz, Michelle; Pollini, Robin A; Fraga, Miguel A; Patterson, Thomas L; Strathdee, Steffanie A

    2008-02-01

    Injection drug use is of increasing concern along the US-Mexico border where Tijuana and Ciudad (Cd.) Juarez are located. Methamphetamine has long been manufactured and trafficked through Mexico, with low rates of use within Mexico. With methamphetamine use now considered epidemic in the United States, and with associated individual and community harms such as HIV, STDs, domestic violence and crime, there is concern that rates of methamphetamine in the Northwestern border regions of Mexico may be rising. We conducted a qualitative study to explore the context of injection drug use in Tijuana and Cd. Juarez and included questions about methamphetamine. Guided in-depth interviews were conducted with 10 male and 10 female injection drug users (IDUs) in Tijuana and 15 male and 8 female IDUs in Cd. Juarez (total N = 43). Topics included types of drug used, injection settings, access to sterile needles and environmental influences. Interviews were taped, transcribed verbatim and translated. Content analysis was conducted to identify themes. The median age of injectors in both cities was 30. Methamphetamine was injected, either alone or in combination with other drugs by injectors in both Tijuana (85%) and Cd. Juarez (17%) in the 6 months previous to interview. Several important themes emerged with respect to methamphetamine use in both cities. IDUs in both cities considered methamphetamine to be widely used in Tijuana and infrequently used in Cd. Juarez, while the converse was true for cocaine. In both cities, stimulant (either cocaine or methamphetamine) use was widespread, with 85% in Tijuana and 83% in Cd. Juarez reporting current use of a stimulant, most often used in combination with heroin. Some injectors reported knowledge of local manufacturing and one had direct experience in making methamphetamine; some cross-border use and trafficking was reported. Injectors reported concerns or experience with serious health effects of methamphetamine such as abscesses or

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

    OpenAIRE

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    OpenAIRE

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

    2010-01-01

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

  13. Duration of Shh signaling contributes to mDA neuron diversity.

    Science.gov (United States)

    Hayes, Lindsay; Ralls, Sherry; Wang, Hui; Ahn, Sohyun

    2013-02-01

    Sonic hedgehog (Shh) signaling is critical for various developmental processes including specification of the midbrain dopamine (mDA) neurons in the ventral mesencephalon (vMes). While the timing of Shh and its response gene Gli1 segregates mDA neurons, their overall lineage contribution to mDA neurons heavily overlaps. Here, we demonstrate that the same set of mDA neuron progenitors sequentially respond to Shh signaling (Gli1 expression), induce Shh expression, and then turn off Shh responsiveness. Thus, at any given developmental stage, cells rarely co-express Shh and Gli1. Using Shh(Cre:GFP) mice to delete the Smoothened receptor in the Shh pathway, we demonstrate that the loss of Shh signaling in Shh expressing cells results in a transient increase in proliferation and subsequent depletion of mDA neuron progenitors in the posterior vMes due to the facilitated cell cycle exit. Moreover, the change in duration of Shh signaling in vMes progenitors altered the timing of the contribution to the ventral tegmental area (VTA) and the substantia nigra pars compacta (SNc) mDA neurons. Taken together, our investigation on the relationship between the Shh-secreting and -responding cells revealed an intricate regulation of induction and cessation of Shh signaling that influences the distribution of mDA neurons in the VTA and SNc.

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

    Directory of Open Access Journals (Sweden)

    Wang Min

    2010-09-01

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

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Rick Shin

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-28

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

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    1995-01-01

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

  20. 美沙酮维持治疗门诊病人滥用"冰毒"行为调查%INVESTIGATION ON METHAMPHETAMINE ABUSE AMONG OPIATE ADDICTS UNDER METHADONE MAINTENANCE TREATMENT

    Institute of Scientific and Technical Information of China (English)

    伏新艳; 高菁; 潘蕾; 方欣; 车驰

    2012-01-01

    Objective: To understand the situation of methamphetamine abuse among opiate addicts during methadone maintenance treatmen( MMT) , found possible risk of drug abuse among them and provide scientific data for the improvement of MMT. Methods: A survey was conducted on 462 patients in 4 MMT clinics with a self - designed questionnaire, the main contents of which were general conditions, drug abuse and physical status of the patients. Urine tests were also made for amphetamine use ( colloidal gold rapid detection ) . Results: Among 462 cases, 86 cases were amphetamine urine test positive, the positive rate was 18. 61% , with male s positive rate 18.52% and female s positive rate 19.05%. The chi -square test showed that there was no significant difference at variables of gender, age, marital status, occupation classification, level of education, between subjects with amphetamine urine test positive and those with negative urine test. Conclusion: There exists amphetamine abuse phenomenon among opiate addicts on MMT.%目的:了解接受美沙酮维持治疗(methadone maintenance treatment.MMT)的阿片类药物成瘾者接受MMT期间是否存在滥用"冰毒"的行为及发生率,为有关部门及时掌握可能存在的隐匿药物滥用风险,为进一步完善MMT措施提供客观数据与科学建议.方法:采用自编的对某地4所美沙酮维持治疗门诊收治的462名患者进行问卷调查,并对调查对象进行苯丙胺类尿检(胶体金法快速检测).结果:462例被调查对象中苯丙胺类尿检阳性86例,阳性检出率达18.61%,其中,男性阳性率占18.52%,女性阳性率占19.05%.X2检验结果显示,男女性别、年龄、婚姻状况、职业、受教育程度尿检阳性率的差异均无统计学意义(P>0.05).结论:接受美沙酮维持治疗的阿片类药物成瘾者有滥用冰毒的现象.

  1. HIV Risk Behavior Among Methamphetamine Users Entering Substance Abuse Treatment in Cape Town, South Africa.

    Science.gov (United States)

    Meade, Christina S; Lion, Ryan R; Cordero, Daniella M; Watt, Melissa H; Joska, John A; Gouse, Hetta; Burnhams, Warren

    2016-10-01

    South Africa is experiencing a growing methamphetamine problem, and there is concern that methamphetamine use may accelerate HIV transmission. There has been little research on the HIV prevention needs of methamphetamine users receiving substance abuse treatment in South Africa. This study assessed the prevalence and correlates of HIV risk behaviors among 269 methamphetamine users entering substance abuse treatment in two clinics in Cape Town. The prevalence of sexual risk behaviors was high among sexually active participants: 34 % multiple partners, 26 % unprotected intercourse with a casual partner, and 24 % sex trading for money/methamphetamine. The strongest predictor of all sexual risk behaviors was concurrent other drug use. Over half had not been HIV tested in the past year, and 25 % had never been tested, although attitudes toward HIV testing were overwhelmingly positive. This population of primarily heterosexual, non-injecting methamphetamine users is a high-risk group in need of targeted HIV prevention interventions. Substance abuse treatment is an ideal setting in which to reach methamphetamine users for HIV services.

  2. MYOCARDIAL LESIONS AFTER LONG-TERM ADMINISTRATION OF METHAMPHETAMINE IN RATS

    Institute of Scientific and Technical Information of China (English)

    Shao-hua Yi; Liang Ren; Tian-tong Yang; Liang Liu; Han Wang; Qian Liu

    2008-01-01

    Objective To demonstrate the myocardial lesion associated with long-term administration of methamphetamine in rats.Methods The experimental models of intoxication of methamphetamine were established in Sprague-Dawley rats.Methamphetamine hydrochloride (3 mg-kg-1·d-1) was subcutaneously injected to rats in methamphetamine-treated group (n=16),and normal saline at the same dose was injected to rats in control group (n=16).After 1 week and 8 weeks of injection,8 rats in each group were sacrificed and their hearts were examined with light microscopy and electron microscopy,respectively.Results After 1 week of methamphetamine exposure,foci of contraction band and cellular degeneration were present in subendocardial myoeardium.Cellular degeneration,myocytolysis,and contraction band necrosis became prominent and extensive in methamphetamine-treated rats after 8 weeks.Hypertrophy,intraeellular vaeuolization,and fibrosis were also observed.The ultrastruetural feature showed marked swelling and degeneration of mitochondria,enlargement of sarcoplasmic reticulum,and dissolution of myofilaments.No obvious cardiac myocyte lesions were observed in rats of control group.Conclusion Methamphetamine abuse daily for a long time may result in an increased risk of cardiovascular lesions similar to cardiomyopathy.

  3. Lobelane inhibits methamphetamine-evoked dopamine release via inhibition of the vesicular monoamine transporter-2.

    Science.gov (United States)

    Nickell, Justin R; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B; Zheng, Guangrong; Crooks, Peter A; Dwoskin, Linda P

    2010-02-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [(3)H]dihydrotetrabenazine binding, inhibition of [(3)H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (K(i) = 45 nM) inhibiting vesicular [(3)H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC(50) = 0.65 microM; I(max) = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC(50) = 0.42 microM, I(max) = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for

  4. Lobelane Inhibits Methamphetamine-Evoked Dopamine Release via Inhibition of the Vesicular Monoamine Transporter-2S⃞

    Science.gov (United States)

    Nickell, Justin R.; Krishnamurthy, Sairam; Norrholm, Seth; Deaciuc, Gabriela; Siripurapu, Kiran B.; Zheng, Guangrong; Crooks, Peter A.

    2010-01-01

    Lobeline is currently being evaluated in clinical trials as a methamphetamine abuse treatment. Lobeline interacts with nicotinic receptor subtypes, dopamine transporters (DATs), and vesicular monoamine transporters (VMAT2s). Methamphetamine inhibits VMAT2 and promotes dopamine (DA) release from synaptic vesicles, resulting ultimately in increased extracellular DA. The present study generated structure-activity relationships by defunctionalizing the lobeline molecule and determining effects on [3H]dihydrotetrabenazine binding, inhibition of [3H]DA uptake into striatal synaptic vesicles and synaptosomes, the mechanism of VMAT2 inhibition, and inhibition of methamphetamine-evoked DA release. Compared with lobeline, the analogs exhibited greater potency inhibiting DA transporter (DAT) function. Saturated analogs, lobelane and nor-lobelane, exhibited high potency (Ki = 45 nM) inhibiting vesicular [3H]DA uptake, and lobelane competitively inhibited VMAT2 function. Lobeline and lobelane exhibited 67- and 35-fold greater potency, respectively, in inhibiting VMAT2 function compared to DAT function. Lobelane potently decreased (IC50 = 0.65 μM; Imax = 73%) methamphetamine-evoked DA overflow, and with a greater maximal effect compared with lobeline (IC50 = 0.42 μM, Imax = 56.1%). These results provide support for VMAT2 as a target for inhibition of methamphetamine effects. Both trans-isomers and demethylated analogs of lobelane had reduced or unaltered potency inhibiting VMAT2 function and lower maximal inhibition of methamphetamine-evoked DA release compared with lobelane. Thus, defunctionalization, cis-stereochemistry of the side chains, and presence of the piperidino N-methyl are structural features that afford greatest inhibition of methamphetamine-evoked DA release and enhancement of selectivity for VMAT2. The current results reveal that lobelane, a selective VMAT2 inhibitor, inhibits methamphetamine-evoked DA release and is a promising lead for the development of a

  5. Methamphetamine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells

    OpenAIRE

    2008-01-01

    The US is currently experiencing an epidemic of methamphetamine (Meth) use as a recreational drug. Recent studies also show a high prevalence of HIV-1 infection among Meth users. We report that Meth enhances HIV-1 infectivity of dendritic cells as measured by multinuclear activation of a galactosidase indicator (MAGI) cell assay, p24 assay, and LTR-RU5 amplification. Meth induces increased HIV-1 infection in association with an increase in the HIV-1 coreceptors, CXCR4 and CCR5, and infection ...

  6. Acute lead poisoning in two users of illicit methamphetamine

    Energy Technology Data Exchange (ETDEWEB)

    Allcott, J.V. III; Barnhart, R.A.; Mooney, L.A.

    1987-07-31

    Acute lead poisoning can present a difficult diagnostic dilemma, with symptoms that mimic those of hepatitis, nephritis, and encephalopathy. The authors report two cases in intravenous methamphetamine users who presented with abnormal liver function values, low hematocrit values, basophilic stippling of red blood cells, and elevated blood lead levels. Both patients excreted large amounts of lead in their urine after treatment with edetic acid, followed by resolution of their symptoms. Lead contamination was proved in one drug sample. Basophilic stippling of the red blood cells was the one key laboratory result that led to the definitive diagnosis in both cases.

  7. Plasma proteomic profiling in HIV-1 infected methamphetamine abusers.

    Directory of Open Access Journals (Sweden)

    Gwenael Pottiez

    Full Text Available We wanted to determine whether methamphetamine use affects a subset of plasma proteins in HIV-infected persons. Plasma samples from two visits were identified for subjects from four groups: HIV+, ongoing, persistent METH use; HIV+, short-term METH abstinent; HIV+, long term METH abstinence; HIV negative, no history of METH use. Among 390 proteins identified, 28 showed significant changes in expression in the HIV+/persistent METH+ group over the two visits, which were not attributable to HIV itself. These proteins were involved in complement, coagulation pathways and oxidative stress. Continuous METH use is an unstable condition, altering levels of a number of plasma proteins.

  8. A comparative study of the effects of methamphetamine on memory in existing and recovering addicts from a South African population

    Directory of Open Access Journals (Sweden)

    Cindy van Wyk

    2012-07-01

    Full Text Available Memory is a complex of systems by which an organism registers, stores and retrieves exposure toan event or experience. Literature purports that methamphetamine users and dependents havebeen found to exhibits signs of memory impairment. The aim of the research was to establishthe possible existence of significant differences in memory in current methamphetamine users,recovering methamphetamine users, and a matched drug naïve control group. Cognitivefunctioning was assessed via a neurocognitive test battery that examined the memory of14 current methamphetamine users, 17 recovering methamphetamine addicts, and 18 drugnaïve control participants who were matched according to the demographic variables of age,gender and educational status. The results indicated that recovering methamphetamine usersexperienced the greatest impairment in memory in comparison to both the control group andcurrent users of methamphetamine. The current users of methamphetamine also experiencedsome impairment in memory functioning in visual acquisition and retention. The poorperformance of the recovering addicts is explained by the juxtaposition of the stimulatingand supplemental effect of methamphetamine as experienced by the current users versus theneurotransmitter depletion and structural changes in the brain experienced by the recoveringaddicts. The control group showed a superior performance since they did not suffer from theneurotoxic effects of methamphetamine.

  9. Methamphetamine decreases CD4 T cell frequency and alters pro-inflammatory cytokine production in a model of drug abuse.

    Science.gov (United States)

    Mata, Mariana M; Napier, T Celeste; Graves, Steven M; Mahmood, Fareeha; Raeisi, Shohreh; Baum, Linda L

    2015-04-01

    The reason co-morbid methamphetamine use and HIV infection lead to more rapid progression to AIDS is unclear. We used a model of methamphetamine self-administration to measure the effect of methamphetamine on the systemic immune system to better understand the co-morbidity of methamphetamine and HIV. Catheters were implanted into the jugular veins of male, Sprague Dawley rats so they could self-administer methamphetamine (n=18) or be given saline (control; n=16) for 14 days. One day after the last operant session, blood and spleens were collected. We measured serum levels of pro-inflammatory cytokines, intracellular IFN-γ and TNF-α, and frequencies of CD4(+), CD8(+), CD200(+) and CD11b/c(+) lymphocytes in the spleen. Rats that self-administered methamphetamine had a lower frequency of CD4(+) T cells, but more of these cells produced IFN-γ. Methamphetamine did not alter the frequency of TNF-α-producing CD4(+) T cells. Methamphetamine using rats had a higher frequency of CD8(+) T cells, but fewer of them produced TNF-α. CD11b/c and CD200 expression were unchanged. Serum cytokine levels of IFN-γ, TNF-α and IL-6 in methamphetamine rats were unchanged. Methamphetamine lifetime dose inversely correlated with serum TNF-α levels. Our data suggest that methamphetamine abuse may exacerbate HIV disease progression by activating CD4 T cells, making them more susceptible to HIV infection, and contributing to their premature demise. Methamphetamine may also increase susceptibility to HIV infection, explaining why men who have sex with men (MSM) and frequently use methamphetamine are at the highest risk of HIV infection.

  10. MDA-9 and GRP78 as potential diagnostic biomarkers for early detection of melanoma metastasis.

    Science.gov (United States)

    Guan, Ming; Chen, Xiaofan; Ma, Yingyu; Tang, Lihua; Guan, Lei; Ren, Xuefeng; Yu, Bo; Zhang, Wei; Su, Bing

    2015-04-01

    Metastatic melanoma, the primary cause of skin cancer-related death, warrants new diagnostic and therapeutic approaches that target the regulatory machinery at molecular level. The heterogeneity and complexity of melanoma result in the difficulty to find biomarkers and targets for early detection and treatment. Here, we investigated metastasis-associated proteins by comparing the proteomic profiles of primary cutaneous melanomas to their matched lymph node metastases, which minimizes heterogeneity among samples from different patients. Results of two-dimensional gel electrophoresis (2-DE) followed by proteomic analysis revealed eight differentially expressed proteins. Among them, seven proteins (α-enolase, cofilin-1, LDH, m-β-actin, Nm23, GRP78, and MDA-9) showed increased and one (annexin A2) showed decreased expression in metastatic lymph node tissues than in primary melanomas. MDA-9 and GRP78 were the most highly expressed proteins in lymph node metastases, which was validated by immunohistochemical staining. Moreover, exosomes from serum samples of metastatic melanoma patients contained higher levels of MDA-9 and GRP78 than those of patients without metastases, indicating the potential of MDA-9 and GRP78 to be biomarkers for early detection of metastasis. Further, small interfering RNA (siRNA)-mediated knockdown confirmed a functional role for MDA-9 and GRP78 to promote cell invasion in the A375 cells. Finally, we showed that GRP78 co-localized with MDA-9 in 293T cells. Taken together, our findings support MDA-9, co-expressed with GRP78, as a melanoma protein associated with lymph node metastasis. Investigating how MDA-9 and GRP78 interact to contribute to melanoma metastasis and disease progression could reveal new potential avenues of targeted therapy and/or useful biomarkers for diagnosis and prognosis.

  11. RIOK3-mediated phosphorylation of MDA5 interferes with its assembly and attenuates the innate immune response.

    Science.gov (United States)

    Takashima, Ken; Oshiumi, Hiroyuki; Takaki, Hiromi; Matsumoto, Misako; Seya, Tsukasa

    2015-04-14

    MDA5 is a cytoplasmic viral double-stranded RNA (dsRNA) sensor and triggers type I interferon (IFN) production. MDA5 assembles along viral dsRNA, leading to the formation of an MDA5 filament required for activating the MAVS adaptor. A recent study has revealed that PP1α and PP1γ phosphatases are responsible for dephosphorylating MDA5 and are essential for its activation. Here, we identified RIO kinase 3 (RIOK3) as a protein kinase that phosphorylates the MDA5 C-terminal region. RIOK3 knockout strongly enhanced type I IFN and IFN-inducible gene expression following measles virus infection. Conversely, the ectopic expression of RIOK3 or a phosphomimetic MDA5-S828D mutation attenuated MDA5-mediated signaling. Moreover, RIOK3-mediated MDA5 phosphorylation impaired MDA5 multimer formation, indicating that MDA5 C-terminal phosphorylation interferes with MDA5 filament formation and suppresses its signaling. Our data revealed a regulatory mechanism underlying the activation of the cytoplasmic viral RNA sensor MDA5 in both uninfected and virus-infected cells.

  12. RIOK3-Mediated Phosphorylation of MDA5 Interferes with Its Assembly and Attenuates the Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Ken Takashima

    2015-04-01

    Full Text Available MDA5 is a cytoplasmic viral double-stranded RNA (dsRNA sensor and triggers type I interferon (IFN production. MDA5 assembles along viral dsRNA, leading to the formation of an MDA5 filament required for activating the MAVS adaptor. A recent study has revealed that PP1α and PP1γ phosphatases are responsible for dephosphorylating MDA5 and are essential for its activation. Here, we identified RIO kinase 3 (RIOK3 as a protein kinase that phosphorylates the MDA5 C-terminal region. RIOK3 knockout strongly enhanced type I IFN and IFN-inducible gene expression following measles virus infection. Conversely, the ectopic expression of RIOK3 or a phosphomimetic MDA5-S828D mutation attenuated MDA5-mediated signaling. Moreover, RIOK3-mediated MDA5 phosphorylation impaired MDA5 multimer formation, indicating that MDA5 C-terminal phosphorylation interferes with MDA5 filament formation and suppresses its signaling. Our data revealed a regulatory mechanism underlying the activation of the cytoplasmic viral RNA sensor MDA5 in both uninfected and virus-infected cells.

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  20. The emerging epidemic of methamphetamine-induced aortic dissections.

    Science.gov (United States)

    Wako, Elizabeth; LeDoux, Denise; Mitsumori, Lee; Aldea, Gabriel S

    2007-01-01

    The clinical presentation, treatment, and outcomes of six consecutive patients presenting with acute aortic dissection secondary to hypertensive crises from methamphetamine use is described. Data were obtained prospectively from the expanded STS clinical database of the division of cardiothoracic surgery at the University of Washington, but reviewed in a retrospective fashion. These patients represent 5.5% of all patients diagnosed and treated for aortic dissection in the same time period (6/109) and 20% of all patients with aortic dissection under the age of 50 years (6/30). We conclude that young patients (methamphetamine. Positive urine tests should be confirmed with chromatography-mass spectrometry (GC-MS). Beta and alpha blockers should be used instead of the more typical beta blockade alone. We recommend the addition and documentation of intense, long-term drug rehabilitation program along with routine periodic clinical and radiographic follow-up to prevent secondary aneurysmal dilation of remaining pathological aorta.

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

    Science.gov (United States)

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

    2017-03-01

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

  2. 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.

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

    Science.gov (United States)

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

    2010-04-02

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

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

    Science.gov (United States)

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

    2011-06-01

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

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

    Science.gov (United States)

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

    2013-02-01

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

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

    Science.gov (United States)

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

    2001-03-01

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

  7. Comparative PET studies of the distribution of ( - )-3,4-methylenedioxy-N-[{sup 11}C]methamphetamine and ( - )-[{sup 11}C]methamphetamine in a monkey brain

    Energy Technology Data Exchange (ETDEWEB)

    Shiue Chyngyann; Shiue, Grace G.; Cornish, Kurtis G.; O' Rourke, Maria F

    1995-04-01

    Carbon-11 labeled ( - )-methamphetamine and ( - )-3,4-methylenedioxy-N-methamphetamine were synthesized by methylation of the corresponding desmethyl precursors with [{sup 11}C]H{sub 3}I in 40-60% yield in a synthesis time of 30 min from EOB with a specific activity of 0.5-1.2 Ci/{mu}M. PET studies in a Rhesus monkey revealed that the uptakes of both compounds in different brain regions were similar, and the retention of radioactivity in these brain regions remained constant throughout the study for the former while it was washed out slowly for the latter. The half-life of ( - )-3,4-methylenedioxy-N-methamphetamine in monkey brain was approximately 70 min. Analyses of arterial plasma by HPLC revealed that 50% of radioactivity in the plasma remained as ( - )-methamphetamine while only 3% remained as ( - )-3,4-methylenedioxy-N-methamphetamine at 60 min post-injection. These results suggest that the uptakes of both compounds in monkey brain are probably not receptor mediated. Rather, blood flow, lipophilicity of the compounds or other transport mechanisms may play a role in their uptakes.

  8. Treatment of Methamphetamine Dependence with Electroconvulsive Therapy (ECT in Iran: A Critical Note.

    Directory of Open Access Journals (Sweden)

    Babak Roshanaei-Moghaddam

    2014-09-01

    Full Text Available This comment article reviews the literature to explore whether the use of ECT for the treatment of methamphetamine dependence can be justified by scientific rationale and/or evidence.This article reviews the literature on the use of ECT in addictive disorders. It describes a patient with methamphetamine dependence treated with ECT. It then offers a historical review of the moral and ethical difficulties encountered in the treatment of addictive disorders. It proposes a dynamic understanding as to why clinicians might deploy such brutal actions in the face of hopeless and emotionally intense encounters.We found no scientific evidence or justification for ECT as a treatment of methamphetamine dependence or as the first line treatment for methamphetamine-induced psychiatric comorbidities.the current available evidence does not support using ECT for the treatment of addictive disorders, and hence is unethical, unacceptable and inhumane and warrants immediate social and political attention.

  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.

  10. Methamphetamine in hair and interpretation of forensic findings in a fatal case.

    Science.gov (United States)

    Beránková, Katerina; Habrdová, Vilma; Balíková, Marie; Strejc, Premysl

    2005-10-04

    Hair analysis for drugs has been developing and is considered a significant tool for distinguishing between recent and long-term drug abuse in forensic and clinical toxicology. Chronic consumption of drugs can gradually induce certain harmful effects on the human organism and can exacerbate some pre-existing diseases. Analysis for drugs in blood or urine in isolation does not provide sufficient information about the history of drug-use by a person and their results cannot be correlated directly with the toxic effects displayed. The chronic abuse of methamphetamine is known to be associated with cardiovascular diseases. During or after autopsy certain types of morphologic alterations are found in the hearts of stimulant addicts. The rapid increase in blood pressure after an intravenous methamphetamine dose can be risky for addicts with arteriosclerosis. However, the anamnestic data about a deceased person may not always be available to explain the pathological findings and to classify the cause of death correctly. The aim of this study was to demonstrate the value of hair analysis for drugs in the context of explaining pathological cardiovascular alterations observed during the autopsy in a case where methamphetamine consumption was involved. In this case, only methamphetamine and metabolites were detected with traces of ephedrine. Ephedrine is the precursor chemical in the illicit synthesis of methamphetamine (known in the Czech Republic as "Pervitin"). The femoral blood level of methamphetamine was 1500 ng/ml. It was documented by a witness that the 31-year-old man died within 1h after an intravenous injection of the drug. The cause of death was established as cerebral edema due to cerebellar bleeding shortly after an intravenous dose of methamphetamine. Findings of methamphetamine in the first three 2-cm hair segments (numbered from the roots) were nearly equal (132+/-9 ng/mg). In the fourth 2-cm segment, it was approximately one-half of previous values. In the

  11. Incubation of Methamphetamine and Palatable Food Craving after Punishment-Induced Abstinence

    OpenAIRE

    Krasnova, Irina N.; Marchant, Nathan J.; Ladenheim, Bruce; McCoy, Michael T.; Panlilio, Leigh V.; Bossert, Jennifer M.; Shaham, Yavin; Cadet, Jean L.

    2014-01-01

    In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed ‘incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeki...

  12. Incubation of methamphetamine and palatable food craving after punishment-induced abstinence.

    Science.gov (United States)

    Krasnova, Irina N; Marchant, Nathan J; Ladenheim, Bruce; McCoy, Michael T; Panlilio, Leigh V; Bossert, Jennifer M; Shaham, Yavin; Cadet, Jean L

    2014-07-01

    In a rat model of drug craving and relapse, cue-induced drug seeking progressively increases after withdrawal from methamphetamine and other drugs, a phenomenon termed 'incubation of drug craving'. However, current experimental procedures used to study incubation of drug craving do not incorporate negative consequences of drug use, which is a common factor promoting abstinence in humans. Here, we studied whether incubation of methamphetamine craving is observed after suppression of drug seeking by adverse consequences (punishment). We trained rats to self-administer methamphetamine or palatable food for 9 h per day for 14 days; reward delivery was paired with a tone-light cue. Subsequently, for one group within each reward type, 50% of the lever-presses were punished by mild footshock for 9-10 days, whereas for the other group lever-presses were not punished. Shock intensity was gradually increased over time. Next, we assessed cue-induced reward seeking in 1-h extinction sessions on withdrawal days 2 and 21. Response-contingent punishment suppressed extended-access methamphetamine or food self-administration; surprisingly, food-trained rats showed greater resistance to punishment than methamphetamine-trained rats. During the relapse tests, both punished and unpunished methamphetamine- and food-trained rats showed significantly higher cue-induced reward seeking on withdrawal day 21 than on day 2. These results demonstrate that incubation of both methamphetamine and food craving occur after punishment-induced suppression of methamphetamine or palatable food self-administration. Our procedure can be used to investigate mechanisms of relapse to drug and palatable food seeking under conditions that more closely approximate the human condition.

  13. 5-HT1A-like receptor activation inhibits abstinence-induced methamphetamine withdrawal in planarians

    OpenAIRE

    Rawls, Scott M.; Shah, Hardik; Ayoub, George; Raffa, Robert B.

    2010-01-01

    No pharmacological therapy is approved to treat methamphetamine physical dependence, but it has been hypothesized that serotonin (5-HT)-enhancing drugs might limit the severity of withdrawal symptoms. To test this hypothesis, we used a planarian model of physical dependence that quantifies withdrawal as a reduction in planarian movement. Planarians exposed to methamphetamine (10 µM) for 60 min, and then placed (tested) into drug-free water for 5 min, displayed less movement (i.e., withdrawal)...

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

    Science.gov (United States)

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

    2002-09-01

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

  15. Arsenicosis status and urinary malondialdehyde (MDA) in people exposed to arsenic contaminated-coal in China.

    Science.gov (United States)

    Wang, Jian Ping; Maddalena, Robyn; Zheng, Baoshan; Zai, Chen; Liu, Faye; Ng, Jack C

    2009-04-01

    The current arsenic exposure condition, arsenicosis prevalence, urinary arsenic and MDA (malondialdehyde) concentrations in people were studied. The study area, a village in Xing Ren County in Guizhou Province, PR China, is a coal-borne arsenicosis endemic area that was identified several decades ago. The residents in Xing Ren have been using coal containing high arsenic levels all their life. Urinary arsenic levels of villagers were 192.2+/-22 microg/g creatinine (n=113) in the coal-borne endemic area (Xing Ren county) and were significantly higher than 63.6+/-5.9 microg/g creatinine (n=30) in a neighbouring control site (a village in Xing Yi county). The urinary MDA concentrations of villagers from the endemic area were also significantly higher compared to those of the control area. There was a strong correlation between age and urinary arsenic and MDA concentrations in the endemic area of Xing Ren; urinary arsenic and MDA levels decreased with age. Fifty out of 113 (44.3%) villagers in the endemic area had arsenicosis symptoms and the prevalence in villagers older than 40 y was 100% in male (92.2% overall). Urinary MDA concentration was significantly higher in people with arsenicosis symptoms in the endemic areas. Oxidative stress (urinary MDA concentration) was strongly related to arsenic exposure but not to the age and smoking habit. Higher urinary arsenic and MDA levels in younger villagers from the endemic area suggest that they are having a higher exposure to coal-borne emitted arsenic because they spend more time indoor. There is an urgent need to develop proper intervention methods in the Guizhou endemic areas in order to reduce the risk to the local communities who are still using arsenic contaminated-coal.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Science.gov (United States)

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

    2010-06-15

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

  18. Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

    Science.gov (United States)

    Volkow, N D; Chang, L; Wang, G J; Fowler, J S; Franceschi, D; Sedler, M; Gatley, S J; Miller, E; Hitzemann, R; Ding, Y S; Logan, J

    2001-12-01

    Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

  19. EFFECTS OF PRENATAL METHAMPHETAMINE EXPOSURE ON BEHAVIORAL AND COGNITIVE FINDINGS AT 7.5 YEARS

    Science.gov (United States)

    Diaz, Sabrina D.; Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Newman, Elana; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn A.; Grotta, Sheri Della; Dansereau, Lynne M.; Neal, Charles; Lester, Barry M.

    2014-01-01

    Objective To examine child behavioral and cognitive outcomes after prenatal exposure to methamphetamine. Study design 412 mother-infant pairs (204 methamphetamine-exposed and 208 unexposed matched comparisons) were enrolled in the Infant Development, Environment and Lifestyle (IDEAL) study. The 151 children exposed to methamphetamine and 147 comparisons who attended the 7.5 year visit were included. Exposure was determined by maternal self-report and/or positive meconium toxicology. Maternal interviews assessed behavioral and cognitive outcomes using the Conner’s Parent Rating Scale – Revised: Short Form (CPRS-R:S). Results After adjusting for covariates, children exposed to methamphetamine had significantly higher cognitive problems subscale scores than comparisons and were 2.8 times more likely to have cognitive problems scores that were above average on the CPRS-R:S No association between prenatal methamphetamine exposure and behavioral problems, measured by the oppositional, hyperactivity and ADHD Index subscales, were found. Conclusion Prenatal methamphetamine exposure was associated with increased cognitive problems which may impact academic achievement and lead to increased negative behavioral outcomes. PMID:24630350

  20. Modulation of the discriminative stimulus effects of cocaine and methamphetamine by the histaminergic system.

    Science.gov (United States)

    Mori, Tomohisa; Narita, Minoru; Onodera, Kenji; Suzuki, Tsutomu

    2002-06-01

    The role of the histaminergic system in the discriminative stimulus effects of cocaine and methamphetamine was examined in rats trained to discriminate between saline and cocaine (10 mg/kg) or methamphetamine (1.0 mg/kg). L-histidine (400 mg/kg), a precursor of histamine, significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. Previous studies have revealed the existence of several histamine receptor types, H1-, H2-, and H3-receptors. These enhancing effects of L-histidine on the discriminative stimulus effects of cocaine and methamphetamine were attenuated by 5.0 mg/kg of pyrilamine (an H1-receptor antagonist), but not by 1.0 mg/kg of zolantidine (an H2-receptor antagonist), suggesting that these enhancing effects of L-histidine were mediated through the activation of H1-receptors. Thioperamide (7.5 mg/kg), an H3-receptor antagonist, also significantly enhanced the discriminative stimulus effects of cocaine and methamphetamine. However, neither pyrilamine nor zolantidine affected the enhancing effects of thioperamide, unlike the results attained with L-histidine. Therefore our findings suggest that the histaminergic system may modify the discriminative stimulus effects of cocaine and methamphetamine mediated through H1- and H3-receptors.

  1. Choosing to Live or Die: Online Narratives of Recovering from Methamphetamine Abuse.

    Science.gov (United States)

    Obong'o, Christopher O; Alexander, Adam C; Chavan, Prachi P; Dillon, Patrick J; Kedia, Satish K

    2017-01-01

    The goal of this study is to explore motivating factors for recovering from methamphetamine abuse. The source of data was 202 anonymous letters and stories submitted to an online support platform for methamphetamine users. Qualitative data were analyzed in Dedoose software using grounded theory methodology. Ten primary motivating factors for recovering from methamphetamine abuse were identified and mapped onto four constructs from the Health Belief Model: (1) perceived susceptibility (learning from others and learning from self); (2) perceived severity (fear of death and declining health); (3) perceived benefits (reconnecting with family, reconnecting with society, and recovering self-esteem); and (4) cues to action (hitting rock bottom, finding God, and becoming pregnant). By using data from an online support group and categorizing emerging themes within a theoretical framework, findings from this study provide a comprehensive understanding of factors involved in recovery from methamphetamine abuse and offer further insights in developing theoretically informed interventions for methamphetamine users. This study suggests the utility of online platforms for obtaining anonymous but unique experiences about drug abuse and recovery. Findings may benefit healthcare professionals, counselors, and researchers by helping to develop theoretically informed interventions for methamphetamine abuse.

  2. Methamphetamine absorption by skin lipids: accumulated mass, partition coefficients, and the influence of fatty acids.

    Science.gov (United States)

    Parker, K; Morrison, G

    2016-08-01

    Occupants of former methamphetamine laboratories, often residences, may experience increased exposure through the accumulation of the methamphetamine in the organic films that coat skin and indoor surfaces. The objectives of this study were to determine equilibrium partition coefficients of vapor-phase methamphetamine with artificial sebum (AS-1), artificial sebum without fatty acids (AS-2), and real skin surface films, herein called skin oils. Sebum and skin oil-coated filters were exposed to vapor-phase methamphetamine at concentrations ranging from 8 to 159 ppb, and samples were analyzed for exposure time periods from 2 h to 60 days. For a low vapor-phase methamphetamine concentration range of ~8-22 ppb, the equilibrium partition coefficient for AS-1 was 1500 ± 195 μg/g/ppb. For a high concentration range of 98-112 ppb, the partition coefficient was lower, 459 ± 80 μg/g/ppb, suggesting saturation of the available absorption capacity. The low partition coefficient for AS-2 (33 ± 6 μg/g/ppb) suggests that the fatty acids in AS-1 and skin oil are responsible for much high partition coefficients. We predict that the methamphetamine concentration in skin lipids coating indoor surfaces can exceed recommended surface remediation standards even for air concentrations well below 1 ppb.

  3. Differences in the symptom profile of methamphetamine-related psychosis and primary psychotic disorders.

    Science.gov (United States)

    McKetin, Rebecca; Baker, Amanda L; Dawe, Sharon; Voce, Alexandra; Lubman, Dan I

    2017-05-01

    We examined the lifetime experience of hallucinations and delusions associated with transient methamphetamine-related psychosis (MAP), persistent MAP and primary psychosis among a cohort of dependent methamphetamine users. Participants were classified as having (a) no current psychotic symptoms, (n=110); (b) psychotic symptoms only when using methamphetamine (transient MAP, n=85); (c) psychotic symptoms both when using methamphetamine and when abstaining from methamphetamine (persistent MAP, n=37), or (d) meeting DSM-IV criteria for lifetime schizophrenia or mania (primary psychosis, n=52). Current psychotic symptoms were classified as a score of 4 or more on any of the Brief Psychiatric Rating Scale items of suspiciousness, hallucinations or unusual thought content in the past month. Lifetime psychotic diagnoses and symptoms were assessed using the Composite International Diagnostic Interview. Transient MAP was associated with persecutory delusions and tactile hallucinations (compared to the no symptom group). Persistent MAP was additionally associated with delusions of reference, thought interference and complex auditory, visual, olfactory and tactile hallucinations, while primary psychosis was also associated with delusions of thought projection, erotomania and passivity. The presence of non-persecutory delusions and hallucinations across various modalities is a marker for persistent MAP or primary psychosis in people who use methamphetamine.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2006-01-01

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

  6. Exogenous PTEN Gene Induces Apoptosis in Breast Carcinoma Cell Line MDA468

    Institute of Scientific and Technical Information of China (English)

    CHEN Qingyong; WANG Chunyou; JIANG Chunfang; CHEN Daoda

    2007-01-01

    The effects and mechanisms of exogenous phosphatase and tensin homolog deleted from chromosome ten (PTEN) gene on phosphatase activity-dependent apoptosis of breast cancer cell line MDA468 were investigated. PTEN gene packaged with lipofectin was transferred into breast cancer cell line MDA468 and parental MDA468 cells served as controls. RT-PCR and Western blot were done to detect the expression of target genes. The expression of phosphospecific protein kinase B (PKB/Akt) and focal adhesion kinase (FAK) protein stimulated by epidermal growth factor (EGF) was also detected. Apoptosis was determined by flow cytometry with a double-staining method using FITC-conjugated annexin V and PI. MDA468 cells transfected with PTEN gene could express PTEN mRNA and protein. PTEN decreased the phosphorylation level of AKT protein and down-regulated FAK protein expression in MDA468 stimulated by EGF. The apoptosis rate was 21.68%. PTEN induced breast cancer apoptosis phosphatase activity-dependently. The mechanism is possibly relatedwith phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/AKT signaling pathway. Those results may provide new clues on the gene therapy in breast cancer.

  7. Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode

    Energy Technology Data Exchange (ETDEWEB)

    Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I., E-mail: evfrolova@UAB.edu

    2016-01-15

    Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. - Highlights: • Both RIG-I and MDA5 detect alphavirus replication. • Alphavirus-induced transcriptional shutoff affects type I IFN induction. • Sensing of alphavirus replication by RIG-I and MDA5 depends on their concentrations. • High basal level of RIG-I and MDA5 allows IFN induction by pathogenic alphaviruses. • This dependence determines the discrepancy between the in vivo and in vitro data.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. 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.

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

    Science.gov (United States)

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

    2008-09-01

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

  11. 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.

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

    Science.gov (United States)

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

    2015-02-01

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

  13. 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...

  14. Methamphetamine-induced toxicity: The role of autophagy?

    Science.gov (United States)

    Roohbakhsh, Ali; Shirani, Kobra; Karimi, Gholamreza

    2016-12-25

    Methamphetamine (METH) is a highly potent and addictive drug with major medical, psychiatric, cognitive, socioeconomic, and legal consequences. It is well absorbed following different routes of administration and distributed throughout the body. METH is known as psychomotor stimulant with potent physiological outcomes on peripheral and central nervous systems, resulting in physical and psychological disorders. Autophagy is a highly conserved and regulated catabolic pathway which is critical for maintaining cellular energy homeostasis and regulating cell growth. The mechanism of autophagy has attracted considerable attention in the last few years because of its recognition as a vital arbiter of death/survival decisions in cells and as a critical defense mechanism in undesirable physiological conditions. The purpose of the current article was to review available evidence to find a relationship between METH toxicity and mechanisms associated with autophagy in different organs.

  15. Report of Methamphetamine use and Cardiomyopathy in Three Patients

    Directory of Open Access Journals (Sweden)

    Roxana Sadeghi

    2012-08-01

    Full Text Available Background Methamphetamine (meth is a stimulant used illegally around the world, including in Iran. Cardiomyopathy and cardiac failure may occur following chronic meth use and may cause the patients referred to the emergency department. Case reportsA 28-year old man and two women, ages 29 and 31-year-old, with a history of meth use, were admitted to the emergency department with severe dyspnea at rest. Each had sinus tachycardia with tachypnea and an echocardiogram that showed severe systolic dysfunction consistent with heart failure. Additional evaluation in the hospital revealed cardiomyopathy with no other etiology other than the meth use. Conclusion:There are several reports that show an increase in frequency of meth use, suggesting that cardiomyopathy and acute heart failure may be a new medical concern.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lúcio Garcia de Oliveira

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-09-01

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

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

    Science.gov (United States)

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

    1998-09-07

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

  20. Methamphetamine compromises gap junctional communication in astrocytes and neurons.

    Science.gov (United States)

    Castellano, Paul; Nwagbo, Chisom; Martinez, Luis R; Eugenin, Eliseo A

    2016-05-01

    Methamphetamine (meth) is a central nervous system (CNS) stimulant that results in psychological and physical dependency. The long-term effects of meth within the CNS include neuronal plasticity changes, blood-brain barrier compromise, inflammation, electrical dysfunction, neuronal/glial toxicity, and an increased risk to infectious diseases including HIV. Most of the reported meth effects in the CNS are related to dysregulation of chemical synapses by altering the release and uptake of neurotransmitters, especially dopamine, norepinephrine, and epinephrine. However, little is known about the effects of meth on connexin (Cx) containing channels, such as gap junctions (GJ) and hemichannels (HC). We examined the effects of meth on Cx expression, function, and its role in NeuroAIDS. We found that meth altered Cx expression and localization, decreased GJ communication between neurons and astrocytes, and induced the opening of Cx43/Cx36 HC. Furthermore, we found that these changes in GJ and HC induced by meth treatment were mediated by activation of dopamine receptors, suggesting that dysregulation of dopamine signaling induced by meth is essential for GJ and HC compromise. Meth-induced changes in GJ and HC contributed to amplified CNS toxicity by dysregulating glutamate metabolism and increasing the susceptibility of neurons and astrocytes to bystander apoptosis induced by HIV. Together, our results indicate that connexin containing channels, GJ and HC, are essential in the pathogenesis of meth and increase the sensitivity of the CNS to HIV CNS disease. Methamphetamine (meth) is an extremely addictive central nervous system stimulant. Meth reduced gap junctional (GJ) communication by inducing internalization of connexin-43 (Cx43) in astrocytes and reducing expression of Cx36 in neurons by a mechanism involving activation of dopamine receptors (see cartoon). Meth-induced changes in Cx containing channels increased extracellular levels of glutamate and resulted in higher

  1. Effect of amlodipine on apoptosis of human breast carcinoma MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective: To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods: Light microscopy was used to determine the effects of amiodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen (PCNA) and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results: Amlodipine concentration of 8.25 Ixmol/L (1/2 of IC50) affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion: The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.

  2. Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

    Science.gov (United States)

    Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

    2010-04-01

    This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

  3. 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.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  5. The vesicular monoamine transporter-2: an important pharmacological target for the discovery of novel therapeutics to treat methamphetamine abuse.

    Science.gov (United States)

    Nickell, Justin R; Siripurapu, Kiran B; Vartak, Ashish; Crooks, Peter A; Dwoskin, Linda P

    2014-01-01

    Methamphetamine abuse escalates, but no approved therapeutics are available to treat addicted individuals. Methamphetamine increases extracellular dopamine in reward-relevant pathways by interacting at vesicular monoamine transporter-2 (VMAT2) to inhibit dopamine uptake and promote dopamine release from synaptic vesicles, increasing cytosolic dopamine available for reverse transport by the dopamine transporter (DAT). VMAT2 is the target of our iterative drug discovery efforts to identify pharmacotherapeutics for methamphetamine addiction. Lobeline, the major alkaloid in Lobelia inflata, potently inhibited VMAT2, methamphetamine-evoked striatal dopamine release, and methamphetamine self-administration in rats but exhibited high affinity for nicotinic acetylcholine receptors (nAChRs). Defunctionalized, unsaturated lobeline analog, meso-transdiene (MTD), exhibited lobeline-like in vitro pharmacology, lacked nAChR affinity, but exhibited high affinity for DAT, suggesting potential abuse liability. The 2,4-dicholorophenyl MTD analog, UKMH-106, exhibited selectivity for VMAT2 over DAT, inhibited methamphetamine-evoked dopamine release, but required a difficult synthetic approach. Lobelane, a saturated, defunctionalized lobeline analog, inhibited the neurochemical and behavioral effects of methamphetamine; tolerance developed to the lobelane-induced decrease in methamphetamine self-administration. Improved drug-likeness was afforded by the incorporation of a chiral N-1,2-dihydroxypropyl moiety into lobelane to afford GZ-793A, which inhibited the neurochemical and behavioral effects of methamphetamine, without tolerance. From a series of 2,5-disubstituted pyrrolidine analogs, AV-2-192 emerged as a lead, exhibiting high affinity for VMAT2 and inhibiting methamphetamine-evoked dopamine release. Current results support the hypothesis that potent, selective VMAT2 inhibitors provide the requisite preclinical behavioral profile for evaluation as pharmacotherapeutics for

  6. Rallying to a cause: the plays of Zakes Mda 1979-1989

    OpenAIRE

    Duggan, Carolyn

    1997-01-01

    Zakes Mda, dubbed one of South Africa's most prolific playwrights, produced his richest and most powerful theatre work during the 70s and 80s. Ironically, it is only in the 90s that he has been acknowledged in his own country as one of its foremost dramatists - ironic since he has recently moved away from drama into the realms of fiction. Fortunately Mda has accumulated a worthy canon of dramatic works, spanning radio and film, as well as theatre, and there is no reason to believe that he wil...

  7. Positron emission tomography (PET) study of the alterations in brain pharmacokinetics of methamphetamine in methamphetamine sensitized animals

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hitoshi [Tohoku Univ., Sendai (Japan). Hospital

    2001-08-01

    I investigated the differences in brain pharmacokinetics of [{sup 11}C]methamphetamine ([{sup 11}C]MAP) in normal and MAP sensitized animals using positron emission tomography (PET). [{sup 11}C]MAP was synthesized by an automated on-line [{sup 11}C]methylation system. I newly produced MAP sensitized dog and monkey by repeated MAP treatment. The maximal level of accumulation of [{sup 11}C]MAP in the sensitized dog brain was 1.4 times higher than that in the control. This result suggests the changes in the pharmacokinetic profile of MAP in the brain affect the development or expression of MAP-induced behavioral sensitization. However, the overaccumulation of [{sup 11}C]MAP in the sensitized monkey brain was not observed due to the influence of anesthesia. (author)

  8. The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Candace R. Lewis

    2013-06-01

    Full Text Available The maternal separation (MS paradigm is an animal model of early life stress. Animals subjected to MS during the first two weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA of various drugs of abuse including cocaine, ethanol, opioids, and amphetamine. Methamphetamine (METH causes great harm to both the individual user and to society; yet, no studies have examined the effects of MS on METH SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2 in the nucleus accumbens (NAc core were also investigated. Long-Evans pups and dams were separated on postnatal days (PND 2-14 for either 180 (MS180 or 15 min (MS15. Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion in 15 2-hr daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.

  9. Methamphetamine-Associated Congestive Heart Failure: Increasing Prevalence and Relationship of Clinical Outcomes to Continued Use or Abstinence.

    Science.gov (United States)

    Sliman, Sean; Waalen, Jill; Shaw, David

    2016-10-01

    The purpose of this study was to determine the prevalence of methamphetamine-associated congestive heart failure (MAC) and to evaluate the relationship between methamphetamine abuse and EF and functional status over time. A retrospective review of records from 2009 to 2014 was carried out. Prevalence of methamphetamine abuse among all patients admitted with CHF was calculated for each of the 6 years of the study (n = 141) and was compared with prevalence of cocaine abuse and alcohol abuse. For patients with two or more admissions during the entire time period, the trajectories of NYHA functional class and EF over time were determined (n = 58). MAC has significantly increased from 1.8 to 5.6 % of total CHF patients admitted (n = 3705). Among patients who stopped using methamphetamine, NYHA functional class significantly improved, while among patients who continued methamphetamine use, NYHA was significantly worsened (p < 0.001). Significantly more patients with improved EF stopped using methamphetamine than continued (p = 0.05). There was a significant increase in the prevalence of MAC during the study period for all CHF patients admitted in our hospital system. Continued methamphetamine use is associated with worsening functional status, while cessation of methamphetamine is associated with improvement in functional status.

  10. Rapid Quantification of Methamphetamine: Using Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Chemometrics

    Science.gov (United States)

    Hughes, Juanita; Ayoko, Godwin; Collett, Simon; Golding, Gary

    2013-01-01

    In Australia and increasingly worldwide, methamphetamine is one of the most commonly seized drugs analysed by forensic chemists. The current well-established GC/MS methods used to identify and quantify methamphetamine are lengthy, expensive processes, but often rapid analysis is requested by undercover police leading to an interest in developing this new analytical technique. Ninety six illicit drug seizures containing methamphetamine (0.1%–78.6%) were analysed using Fourier Transform Infrared Spectroscopy with an Attenuated Total Reflectance attachment and Chemometrics. Two Partial Least Squares models were developed, one using the principal Infrared Spectroscopy peaks of methamphetamine and the other a Hierarchical Partial Least Squares model. Both of these models were refined to choose the variables that were most closely associated with the methamphetamine % vector. Both of the models were excellent, with the principal peaks in the Partial Least Squares model having Root Mean Square Error of Prediction 3.8, R2 0.9779 and lower limit of quantification 7% methamphetamine. The Hierarchical Partial Least Squares model had lower limit of quantification 0.3% methamphetamine, Root Mean Square Error of Prediction 5.2 and R2 0.9637. Such models offer rapid and effective methods for screening illicit drug samples to determine the percentage of methamphetamine they contain. PMID:23936058

  11. Rapid quantification of methamphetamine: using attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR and chemometrics.

    Directory of Open Access Journals (Sweden)

    Juanita Hughes

    Full Text Available In Australia and increasingly worldwide, methamphetamine is one of the most commonly seized drugs analysed by forensic chemists. The current well-established GC/MS methods used to identify and quantify methamphetamine are lengthy, expensive processes, but often rapid analysis is requested by undercover police leading to an interest in developing this new analytical technique. Ninety six illicit drug seizures containing methamphetamine (0.1%-78.6% were analysed using Fourier Transform Infrared Spectroscopy with an Attenuated Total Reflectance attachment and Chemometrics. Two Partial Least Squares models were developed, one using the principal Infrared Spectroscopy peaks of methamphetamine and the other a Hierarchical Partial Least Squares model. Both of these models were refined to choose the variables that were most closely associated with the methamphetamine % vector. Both of the models were excellent, with the principal peaks in the Partial Least Squares model having Root Mean Square Error of Prediction 3.8, R(2 0.9779 and lower limit of quantification 7% methamphetamine. The Hierarchical Partial Least Squares model had lower limit of quantification 0.3% methamphetamine, Root Mean Square Error of Prediction 5.2 and R(2 0.9637. Such models offer rapid and effective methods for screening illicit drug samples to determine the percentage of methamphetamine they contain.

  12. Rapid quantification of methamphetamine: using attenuated total reflectance fourier transform infrared spectroscopy (ATR-FTIR) and chemometrics.

    Science.gov (United States)

    Hughes, Juanita; Ayoko, Godwin; Collett, Simon; Golding, Gary

    2013-01-01

    In Australia and increasingly worldwide, methamphetamine is one of the most commonly seized drugs analysed by forensic chemists. The current well-established GC/MS methods used to identify and quantify methamphetamine are lengthy, expensive processes, but often rapid analysis is requested by undercover police leading to an interest in developing this new analytical technique. Ninety six illicit drug seizures containing methamphetamine (0.1%-78.6%) were analysed using Fourier Transform Infrared Spectroscopy with an Attenuated Total Reflectance attachment and Chemometrics. Two Partial Least Squares models were developed, one using the principal Infrared Spectroscopy peaks of methamphetamine and the other a Hierarchical Partial Least Squares model. Both of these models were refined to choose the variables that were most closely associated with the methamphetamine % vector. Both of the models were excellent, with the principal peaks in the Partial Least Squares model having Root Mean Square Error of Prediction 3.8, R(2) 0.9779 and lower limit of quantification 7% methamphetamine. The Hierarchical Partial Least Squares model had lower limit of quantification 0.3% methamphetamine, Root Mean Square Error of Prediction 5.2 and R(2) 0.9637. Such models offer rapid and effective methods for screening illicit drug samples to determine the percentage of methamphetamine they contain.

  13. Initial Feasibility and Acceptability of a Comprehensive Intervention for Methamphetamine-Using Pregnant Women in South Africa

    Directory of Open Access Journals (Sweden)

    Hendrée E. Jones

    2014-01-01

    Full Text Available The purpose of the present study was to determine the feasibility, acceptability, and initial efficacy of a women-focused intervention addressing methamphetamine use and HIV sexual risk among pregnant women in Cape Town, South Africa. A two-group randomized pilot study was conducted, comparing a women-focused intervention for methamphetamine use and related sexual risk behaviors to a psychoeducational condition. Participants were pregnant women who used methamphetamine regularly, had unprotected sex in the prior month, and were HIV-negative. Primary maternal outcomes were methamphetamine use in the past 30 days, frequency of unprotected sexual acts in the past 30 days, and number of antenatal obstetrical appointments attended. Primary neonatal outcomes were length of hospital stay, birth weight, and gestational age at delivery. Of the 57 women initially potentially eligible, only 4 declined to participate. Of the 36 women who were eligible and enrolled, 92% completed all four intervention sessions. Women in both conditions significantly reduced their methamphetamine use and number of unprotected sex acts. Therefore, delivering comprehensive interventions to address methamphetamine use and HIV risk behaviors among methamphetamine-using pregnant women is feasible in South Africa. Further testing of these interventions is needed to address methamphetamine use in this vulnerable population.

  14. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Q.; Langereis, M.A.; Lork, M.; Nguyen, M.H.; Hato, S.V.; Lanke, K.H.W.; Emdad, L.; Bhoopathi, P.; Fisher, P.B.; Lloyd, R.E.; Kuppeveld, F.J.M. van

    2014-01-01

    RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppress interfer

  15. Enterovirus 2Apro targets MDA5 and MAVS in infected cells

    NARCIS (Netherlands)

    Feng, Qian; Langereis, Martijn A; Lork, Marie; Nguyen, Mai; Hato, Stanleyson V; Lanke, Kjerstin; Emdad, Luni; Bhoopathi, Praveen; Fisher, Paul B; Lloyd, Richard E; van Kuppeveld, Frank J M

    2014-01-01

    UNLABELLED: RIG-I-like receptors (RLRs) MDA5 and RIG-I are key players in the innate antiviral response. Upon recognition of viral RNA, they interact with MAVS, eventually inducing type I interferon production. The interferon induction pathway is commonly targeted by viruses. How enteroviruses suppr

  16. MDA5 Detects the Double-Stranded RNA Replicative Form in Picornavirus-Infected Cells

    Directory of Open Access Journals (Sweden)

    Qian Feng

    2012-11-01

    Full Text Available RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C, a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions.

  17. Expression pattern of mda-7/IL-24 receptors in liver cancer cell lines

    Institute of Scientific and Technical Information of China (English)

    Hong Zhu; Zhi-Bin Yang

    2009-01-01

    BACKGROUND: The mda-7/IL-24 receptor belongs to the typeⅡ cytokine receptor family, and its two heterodimeric receptors are IL-22R1/IL-20R2 and IL-20R1/IL-20R2. Mda-7/IL-24 receptor expression in liver cancer cell lines has not yet been described. This information may be helpful for further clinical gene therapy. METHODS: With normal skin total RNA as template, the cDNA sequences of IL-20R1, IL-20R2 and IL-22R were ampliifed by RT-PCR. Total RNA was extracted from cultured liver cancer cell lines and a normal liver cell line, then detected by northern blotting, and the expression of mda-7/IL-24 receptors was analyzed. RESULTS: PLC/PRF/5 and SMMC-7721 expressed IL-20R1;BEL-7402, Hep3B, HepG2, and PLC/PRF/5 expressed IL-20R2; and HepG2 and PLC/PRF/5 expressed IL-22R. Only HepG2 expressed the IL-22R/IL-20R2 receptor complex. PLC/PRF/5 completely expressed both heterodimeric receptors. Huh-7, QGY-7701 and WRL-68 did not express the IL-24 receptor. CONCLUSION: Complete mda-7/IL-24 receptors are seldom expressed in liver cancer cell lines.

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

    Science.gov (United States)

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

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

  19. 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.

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

    Science.gov (United States)

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

    2009-01-01

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

  1. 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...

  2. 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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

    Castellano, C

    1979-03-29

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

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sadeghi

    2015-12-01

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

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

    Science.gov (United States)

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

    2008-03-01

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

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

    Science.gov (United States)

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

    2008-09-01

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

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

    Science.gov (United States)

    Norman, Amanda; Hulse, Gary Kenneth

    2017-01-01

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

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

    Science.gov (United States)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2010-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-08-21

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

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

    Science.gov (United States)

    Liu, W; Shen, M

    1999-05-01

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

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

    Science.gov (United States)

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

    2003-01-28

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

  15. 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...

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

    Science.gov (United States)

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

    2006-08-01

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

  17. Effect of add-on valproate on craving in methamphetamine depended patients: A randomized trial

    Science.gov (United States)

    Kheirabadi, Gholam Reza; Ghavami, Masoud; Maracy, Mohammad Reza; Salehi, Mehrdad; Sharbafchi, Mohammad Reza

    2016-01-01

    Background: Methamphetamine dependence lead to the compulsive use, loss of control, and social and occupational dysfunctions. This study aimed to compare the effect of valproate in reducing the craving in methamphetamine dependents. Materials and Methods: This is a randomized, double-blind, controlled clinical trial on 40 men of 18–40 years old referred to Noor Hospital during December 2012–September 2013 in Isfahan, Iran. The subjects participated in matrix program and randomly were divided into two groups of valproate and placebo. A 4-months program of intervention with valproate or placebo was arranged for each group. The rate of craving to methamphetamine and positive methamphetamine urine tests were evaluated in both groups every 2 weeks using cocaine craving questionnaire-brief (CCQ-Brief) and urine test. After the 4 months (active treatment with valproate and placebo), the drug was tapered and discontinued within 10 days, and patients were introduced to self-help groups and monitored regularly on a weekly basis over another 3 months. Collected data were analyzed with SPSS 20 using analysis of covariance repeated measure, Chi-square, and t-test. Results: CCQ score of the intervention group was significantly less than the placebo group (P craving to methamphetamine. PMID:27656618

  18. Crystal methamphetamine and sexual sociality in an urban gay subculture: an elective affinity.

    Science.gov (United States)

    Green, Adam Isaiah; Halkitis, Perry N

    2006-01-01

    This paper draws on 49 qualitative interviews to explore the contextual antecedents of methamphetamine use in a sample of gay and bisexual Manhattan men. The paper distinguishes itself from the public health literature on crystal methamphetamine use in this population by shifting the analytic focus from individual-level factors of drug use to the role of social context. While individual-level factors--including self esteem and social awkwardness--are related to methamphetamine use, we argue that these factors arise in and are exacerbated by interactional pressures attendant to Manhattan's gay sexual subculture, which revolve around the expectation of peak sexual performance. Because methamphetamine is associated with increased self-esteem, increased libido, greater sexual endurance, diminished sexual inhibition, and a higher threshold for pain, the drug is used strategically by gay and bisexual men to negotiate sexual sociality and increase sexual pleasure. Hence, we suggest that there exists an elective affinity between Manhattan's gay sexual subculture and the particular pharmacological effects of methamphetamine-whereby the former strongly favours the latter as a systematic pattern of response. In turn, this relationship is linked to unsafe sexual practices or the social conditions that put gay men 'at risk of risk' of HIV infection.

  19. Methamphetamine treatment outcomes among gay men attending a LGBTI-specific treatment service in Sydney, Australia.

    Science.gov (United States)

    Lea, Toby; Kolstee, Johann; Lambert, Sarah; Ness, Ross; Hannan, Siobhan; Holt, Martin

    2017-01-01

    Gay and bisexual men (GBM) report higher rates of methamphetamine use compared to heterosexual men, and thus have a heightened risk of developing problems from their use. We examined treatment outcomes among GBM clients receiving outpatient counseling at a lesbian, gay, bisexual, transgender and intersex (LGBTI)-specific, harm reduction treatment service in Sydney, Australia. GBM receiving treatment for methamphetamine use from ACON's Substance Support Service between 2012-15 (n = 101) were interviewed at treatment commencement, and after 4 sessions (n = 60; follow-up 1) and 8 sessions (n = 32; follow-up 2). At each interview, clients completed measures of methamphetamine use and dependence, other substance use, injecting risk practices, psychological distress and quality of life. The median age of participants was 41 years and 56.4% identified as HIV-positive. Participants attended a median of 5 sessions and attended treatment for a median of 112 days. There was a significant reduction in the median days of methamphetamine use in the previous 4 weeks between baseline (4 days), follow-up 1 (2 days) and follow-up 2 (2 days; p = .001). There was a significant reduction in the proportion of participants reporting methamphetamine dependence between baseline (92.1%), follow-up 1 (78.3%) and follow-up 2 (71.9%, p LGBTI-specific treatment service.

  20. Toward a Better Understanding of Non-Addicted, Methamphetamine-Using, Men who Have Sex with Men (MSM) in Atlanta.

    Science.gov (United States)

    Dew, Brian J

    2010-05-14

    Methamphetamine use has increasingly become linked with sexual risk behaviors among men have sex with men (MSM). Yet, the majority of research has been done with methamphetamine dependent MSM or with samples in which addiction to the substance was not evaluated. Furthermore, research with methamphetamine-using MSM in the Southern U.S. is lacking. In this study, focus groups and in-depth interviews were conducted in order to understand the motives, context, and other facilitators and barriers of methamphetamine use among non-addicted MSM residing in Atlanta. Participants included 30 non-addicted, methamphetamine-using MSM and 16 local mental and public health officials. Findings from the first of this two-phase formative research project will result in the initial development of a community-tested, culturally-specific social marketing campaign and an individual-based intervention based in HIV-testing facilities.

  1. Methamphetamine and fluoxetine treatment of a child with attention-deficit hyperactivity disorder and obsessive-compulsive disorder.

    Science.gov (United States)

    Bussing, R; Levin, G M

    1993-01-01

    ABSTRACT An 11-year-old child with obsessive-compulsive disorder, major depression, and attentiondeficit hyperactivity disorder was successfully treated with a combination of fluoxetine (mean 30 mg daily) and methamphetamine (sustained release 10 mg daily). Methamphetamine was selected because of the desirability of avoiding stimulants whose commercial formulations contain food dyes (this child appeared sensitive to tartrazine in dextroamphetamine and other agents), whose effects on hepatic metabolism were minimal (unlike methylphenidate) and whose mechanism of action is reliably rapid (unlike pemoline). Although methamphetamine carries the stigma of an abusable drug and has been implicated in neurotoxicity in animals when used at extremely high doses, methamphetamine may have certain advantages over other psychostimulants in some clinical situations. The combined use of fluoxetine and methamphetamine did not appear to be associated with significant adverse effects.

  2. PENGARUH SUPLEMENTASI MADU KELENGKENG TERHADAP KADAR TSA DAN MDA TIKUS PUTIH YANG DIINDUKSI TIMBAL (Pb

    Directory of Open Access Journals (Sweden)

    Kamilatussaniah Kamilatussaniah

    2016-04-01

    Full Text Available Timbal (Pb merupakan salah satu logam berat yang berasal dari emisi pembakaran bahan bakar. Peningkatan penggunaan bahan bakar pada mesin industri dan kendaraan bermotor menyebabkan peningkatan kadar Pb di udara. Masuknya Pb ke dalam tubuh akan mengganggu keseimbangan molekul lain sehingga menjadi radikal bebas. Ketidakseimbangan antara radikal bebas dengan antioksidan menyebabkan stres oksidatif yang ditandai dengan menurunnya total satus antioksidan (TSA dan meningkatnya malondialdehid (MDA. Madu kelengkeng adalah suplemen kesehatan yang mengandung flavonoid, vitamin C, vitamin E dan beta karoten yang berperan sebagai antioksidan. Penelitian ini bertujuan untuk mengetahui pengaruh madu kelengkeng terhadap kadar TSA dan MDA darah tikus putih yang diinduksi Pb. Desain penelitian ini adalah eksperimental dengan 25 ekor tikus putih jantan galur Wistar yang dibagi dalam 5 kelompok, yaitu kelompok A (tikus normal, B (tikus dengan induksi Pb 10 mg/kgBB dan C, D, E merupakan kelompok perlakuan suplementasi madu secara berturut-turut 0,45, 0,9, 1,8 ml/200 gramBB dan induksi Pb 10 mg/kgBB selama 14 hari. Data TSA dan MDA dianalisis menggunakan one way anova dan uji LSD untuk mengetahui perbedaan setiap kelompok. Hasil penelitian menunjukkan madu dengan dosis 1,8 ml/200 gramBB dapat meningkatkan kadar TSA dan menurunkan kadar MDA secara signifikan. Simpulan dari penelitian ini adalah madu dapat meningkatkan kadar TSA dan menurunkan kadar MDA pada tikus putih yang diinduksi Pb. Lead (Pb is heavy metal which comes from waste fuel emissions. Increased use of fuel in industrial machinery and vehicles causes increased levels of lead in the air. The entry of Pb into the body will disturb the ballance other molecules and became a free radicals. The imbalance between free radicals and antioxidants cause oxidative stress which characterized by decreased total antioxidant statue (TAS and increased malondialdehid (MDA. Longan honey is health suplement which

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

    Directory of Open Access Journals (Sweden)

    Casalotti Stefano O

    2008-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-06-11

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

  5. Mechanism of Methamphetamine Intoxication and Its Medical Identification%甲基苯丙胺的中毒机制及中毒死亡法医学鉴定

    Institute of Scientific and Technical Information of China (English)

    高卫民; 宛洋; 毛瑞明; 米丽; 杜中波; 曹志鹏; 朱宝利

    2012-01-01

    甲基苯丙胺是苯丙胺类中枢神经系统兴奋剂的代表药物,近年来已成为当今世界上危害最大的毒品之一.本文对甲基苯丙胺在体内的作用机制、分布和代谢情况、中毒机理、对心血管及中枢神经系统的影响以及有关的法医学鉴定现状进行综述.%Methamphetamine(MA) is a representative drug of amphetamine-type stimulants for central nervous system and has become one of the most dangerous drugs in the world recently. The present article reviews the pharmacological effects, distribution, metabolism, intoxication mechanism, the effects of MA on cardiovascular and central nervous systems of MA, and the current situation of forensic investigation on MA.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hedi Schelleman

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  9. 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.

  10. Examining the relationships between prenatal methamphetamine exposure, early adversity, and child neurobehavioral disinhibition.

    Science.gov (United States)

    Abar, Beau; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Smith, Lynne M; Arria, Amelia; Huestis, Marilyn; Della Grotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2013-09-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother-infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed.

  11. Identification of impurities and statistical classification of methamphetamine hydrochloride drugs seized in the China

    Science.gov (United States)

    Zhang, Jian Xin; Zhang, Da Ming; Han, Xu Guang

    2008-01-01

    A total of 48 methamphetamine hydrochloride samples from eight seizures were analyzed using gas chromatography–mass spectrometry (GC–MS) and a flame ionization detector (GC–FID). Major impurities detected include 1,2-dimethyl-3-phenylaziridine, Ephedrine/pseudoephedrine, 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene. These data are suggestive of ephedrine/pseudoephedrine as the main precursor of the methamphetamine hydrochloride samples seized during 2006–2007. Additionally the presence of 1,3-dimethyl-2-phenylnaphthalene, 1-benzyl-3-methylnaphthalene is indicative that six seizures were synthesized via the more specific ephedrine/hydriodic acid/red phosphorus method. In addition, five impurities were found for the first time in methamphetamine hydrochloride samples. Seventeen impurity peaks were selected from the GC–FID chromatograms. The peak areas of the selected peaks were then grouped for cluster analysis. PMID:19008060

  12. Effects of methamphetamine administration on information gathering during probabilistic reasoning in healthy humans.

    Directory of Open Access Journals (Sweden)

    Anna O Ermakova

    Full Text Available Jumping to conclusions (JTC during probabilistic reasoning is a cognitive bias repeatedly demonstrated in people with schizophrenia and shown to be associated with delusions. Little is known about the neurochemical basis of probabilistic reasoning. We tested the hypothesis that catecholamines influence data gathering and probabilistic reasoning by administering intravenous methamphetamine, which is known to cause synaptic release of the catecholamines noradrenaline and dopamine, to healthy humans whilst they undertook a probabilistic inference task. Our study used a randomised, double-blind, cross-over design. Seventeen healthy volunteers on three visits were administered either placebo or methamphetamine or methamphetamine preceded by amisulpride. In all three conditions participants performed the "beads" task in which participants decide how much information to gather before making a probabilistic inference, and which measures the cognitive bias towards jumping to conclusions. Psychotic symptoms triggered by methamphetamine were assessed using Comprehensive Assessment of At-Risk Mental States (CAARMS. Methamphetamine induced mild psychotic symptoms, but there was no effect of drug administration on the number of draws to decision (DTD on the beads task. DTD was a stable trait that was highly correlated within subjects across visits (intra-class correlation coefficients of 0.86 and 0.91 on two versions of the task. The less information was sampled in the placebo condition, the more psychotic-like symptoms the person had after the methamphetamine plus amisulpride condition (p = 0.028. Our results suggest that information gathering during probabilistic reasoning is a stable trait, not easily modified by dopaminergic or noradrenergic modulation.

  13. The effect of baicalein on the expression of SATB1 in MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    Xiaoyan Gao; Xingcong Ma; Yinan Ma; Xinghuan Xue; Shuqun Zhang

    2014-01-01

    Objective:Baicalein had been proved to have anti-cancer activity in vitro and in vivo, including the inhibition of malignant proliferation, migration, adhesion and invasion of many kinds of cancer cel s. The special AT-rich sequence binding protein 1 (SATB1) is a tissue-specific expression of nuclear matrix-binding protein and is reported to be a breast cancer“gene group organizer”. Previous studies have shown that SATB1 is involved in the growth, metastasis and prognosis of breast cancer. The present study was aimed to investigate whether baicalein inhibits the proliferation and migration of MDA-MB-231 human breast cancer cel s through down-regulation of the SATB1 expression. Methods:MDA-MB-231 cel s were treated for 24 h, 48 h and 72 h with various concentrations of baicalein (0, 5, 10, 20, 40 and 80μM) respectively. Then, the proliferation and migration of MDA-MB-231 cel s fol owing treatment with baicalein were determined using colorimetric 3-(4, 5-dimethylthia-zol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) and wound healing assays. Thereafter, western blot analysis was performed to detect the changes of SATB1 protein expression in MDA-MB-231 cel s. Results:Along with the prolongation of time and increase of drug concentration, inhibitory ef ect of baicalein on proliferation and migration of MDA-MB-231 cel s gradual y in-creased, in a time-and dose-dependent manner (P<0.05). Meanwhile, after treated with baicalein in dif erent concentrations for 48 h, the level of SATB1 protein expression of MDA-MB-231 cel s decreased obviously, in a dose-dependent manner (P<0.05). Conclusion:Baicalein inhibits breast cancer cel proliferation and suppresses its invasion and metastasis by reducing cel migration possibly by down-regulation of the SATB1 protein expression, indicating that baicalein is a potential therapeutic agent for human breast cancer.

  14. Effect of methamphetamine dependence on heart rate variability.

    Science.gov (United States)

    Henry, Brook L; Minassian, Arpi; Perry, William

    2012-05-01

    Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age- and gender-matched drug-free comparison subjects. HRV was assessed using time domain, frequency domain, and non-linear entropic analyses in 17 previously METH-dependent and 21 drug-free comparison individuals during a 5 minute rest period. The METH-dependent group demonstrated significant reduction in HRV, reduced parasympathetic activity, and diminished heartbeat complexity relative to comparison participants. More recent METH use was associated with increased sympathetic tone. Chronic METH exposure may be associated with decreased HRV, impaired vagal function, and reduction in heart rate complexity as assessed by multiple methods of analysis. We discuss and review evidence that impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged METH use.

  15. Maternal depression and neurobehavior in newborns prenatally exposed to methamphetamine

    Science.gov (United States)

    Paz, Monica S.; Smith, Lynne M.; LaGasse, Linda L.; Derauf, Chris; Grant, Penny; Shah, Rizwan; Arria, Amelia; Huestis, Marilyn; Haning, William; Strauss, Arthur; Grotta, Sheri Della; Liu, Jing; Lester, Barry M.

    2009-01-01

    Background The effects of maternal depression on neonatal neurodevelopment in MA exposed neonates have not been well characterized. Objective To determine the neurobehavioral effects of maternal depressive symptoms on neonates exposed and not exposed to methamphetamine (MA) using the NICU Network Neurobehavioral Scale (NNNS). Design The purpose of the IDEAL study is to determine the effects of prenatal MA exposure on child outcome. IDEAL screened 13,808 subjects, 1632 were eligible and consented and 176 mothers were enrolled. Only biological mothers with custody of their child at the one-month visit (n=50 MA; n=86 comparison) had the Addiction Severity Index (ASI) administered. The NNNS was administered to the neonate by an examiner blinded to MA exposure within the first five days of life. General Linear Models tested the effects of maternal depression and prenatal MA exposure on NNNS outcomes, with and without covariates. Significance was accepted at p<.05. Results After adjusting for covariates, regardless of exposure status, maternal depressive symptoms were associated with lower handling and arousal scores, elevated physiological stress scores and an increased incidence of hypotonicity. When adjusting for covariates, MA exposure was associated with lower arousal and higher lethargy scores. Conclusions Maternal depressive symptoms are associated with neurodevelopmental patterns of decreased arousal and increased stress. Prenatal MA exposure combined with maternal depression was not associated with any additional neonatal neurodevelopmental differences. PMID:19059478

  16. Exercise protects against methamphetamine-induced aberrant neurogenesis

    Science.gov (United States)

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-01-01

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. PMID:27677455

  17. Induction of testicular damage by daily methamphetamine administration in rats.

    Science.gov (United States)

    Lin, Ji-Fan; Lin, Yi-Hsuan; Liao, Po-Cheng; Lin, Yi-Chia; Tsai, Te-Fu; Chou, Kuang-Yu; Chen, Hung-En; Tsai, Shiow-Chwen; Hwang, Thomas I-Sheng

    2014-02-28

    Methamphetamine (METH)-induced brain damage and apoptosis within the central nervous system are well documented. This study was conducted to investigate the toxic effects of daily METH administration on the testes in a rat model. Male Sprague-Dawley rats (5 weeks old, ~100 g, n = 64) were divided into two groups and treated with vehicle (saline, control) or METH (10 mg/kg) for 15, 30, 60 and 90 days. The results showed that daily administration of METH decreased the body, testicular and epididymis weights as well as the serum levels of total testosterone. The increased apoptotic index (Bad/Bcl2 expression ratio) and levels of cleaved caspase-3 indicated that apoptosis had occurred in the testes of the METH-treated rats. The oxidative stress levels increased as the reduced and oxidized glutathione (GSH/GSSG) ratio decreased. The overall sperm counts decreased at 15 and 90 days, where- as morphologically abnormal sperm counts increased at 30, 60 and 90 days in the METH-treated rats. This study demonstrates that daily exposure to METH significantly reduced the number and quality of sperm in rats. The underlying pathophysiological mechanisms likely include the reduction of serum testosterone levels and the increase of oxidative stress and apoptosis in the rat testes.

  18. Modification of Monoaminergic Activity by MAO Inhibitors Influences Methamphetamine Actions

    Directory of Open Access Journals (Sweden)

    Junichi Kitanaka

    2006-01-01

    Full Text Available Methamphetamine (METH abuse is a serious health and social problem worldwide. At present, however, there are no effective medications for the treatment of METH abuse. Of the intracellular METH target proteins, monoamine oxidase (MAO is involved in the regulation of monoaminergic tone in the brain, resulting in the modulation of METHinduced behavioral abnormalities in mammals. The METH-induced expression of increased motor activity, stereotypy, and sensitization is closely associated with monoaminergic transmission in the brain. Modifi cation of MAO activity by MAO inhibitors can influence METH action. Of the MAO inhibitors, the propargylamine derivative clorgyline, an irreversible MAO-A inhibitor, effectively blocks METH-induced hyperlocomotion and behavioral sensitization in rodents. Analysis of the associated monoaminergic activity indicates an involvement of altered striatal serotonergic transmission as well as an increased dopaminergic tone. Some effects of MAO inhibitors on METH action appear to be independent of MAO, suggesting complex mechanisms of action of MAO inhibitors in METH abuse. This review describes current research to find effective treatment for METH abuse, using MAO inhibitors.

  19. HIV-1, Methamphetamine and Astrocytes at Neuroinflammatory crossroads

    Directory of Open Access Journals (Sweden)

    Kathleen eBorgmann

    2015-10-01

    Full Text Available As a popular psychostimulant, methamphetamine (METH use leads to long-lasting, strong euphoric effects. While METH abuse is common in the general population, between 10-15% of human immunodeficiency virus-1 (HIV-1 patients report having abused METH. METH exacerbates the severity and onset of HIV-1-associated neurocognitive disorders (HAND through direct and indirect mechanisms. Repetitive METH use decreases adherence to antiretroviral drug regimens, increasing the likelihood of HIV-1 disease progression towards AIDS. METH exposure also directly affects both innate and adaptive immunity, altering lymphocyte number and activity, cytokine signaling, phagocytic function, and CNS infiltration through the blood brain barrier. Further, METH triggers the neuronal dopamine reward pathway and leads to altered neuronal activity and direct toxicity. Concurrently, METH and HIV-1 alter the neuroimmune balance and induce neuroinflammation. Neuroinflammation modulates a wide range of brain functions including neuronal signaling and activity, glial activation, viral infection, oxidative stress and excitotoxicity. Pathologically, glial activation is a hallmark of both HIV-1 and METH-associated neuroinflammation. Significant commonality exists in the neurotoxic mechanisms for both METH and HAND; however, the pathways dysregulated in astroglia during METH exposure are less clear. Thus alterations in astrocyte intracellular signaling pathways, gene expression and function during METH and HIV-1 comorbidity, neuroinflammation and HAND are carefully reviewed. Interventions targeting astrocytes in HAND and METH are presented as potential novel therapeutic approaches.

  20. Role of PUMA in methamphetamine-induced neuronal apoptosis.

    Science.gov (United States)

    Chen, Chuanxiang; Qincao, Litao; Xu, Jingtao; Du, Sihao; Huang, Enping; Liu, Chao; Lin, Zhoumeng; Xie, Wei-Bing; Wang, Huijun

    2016-01-05

    Exposure to methamphetamine (METH), a widely used illicit drug, has been shown to cause neuron apoptosis. p53 upregulated modulator of apoptosis (PUMA) is a key mediator in neuronal apoptosis. This study aimed to examine the effects of PUMA in METH-induced neuronal apoptosis. We determined PUMA protein expression in PC12 cells and SH-SY5Y cells after METH exposure using western blot. We also observed the effect of METH on neuronal apoptosis after silencing PUMA expression with siRNA using TUNEL staining and flow cytometry. Additionally, to investigate possible mechanisms of METH-induced PUMA-mediated neuronal apoptosis, we measured the protein expression of apoptotic markers, including cleaved caspase-3, cleaved PARP, Bax, B-cell leukemia/lymphoma-2 (Bcl-2) and cytochrome c (cyto c), after METH treatment with or without PUMA knockdown. Results showed that METH exposure induced cell apoptosis, increased PUMA protein levels, activated caspase-3 and PARP, elevated Bax and reduced Bcl-2 expression, as well as increased the release of cyto c from mitochondria to the cytoplasm in both PC12 and SH-SY5Y cells. All these effects were attenuated or reversed after silencing PUMA. A schematic depicting the role of PUMA in METH-induced mitochondrial apoptotic pathway was proposed. Our results suggest that PUMA plays an important role in METH-triggered apoptosis and it may be a potential target for ameliorating neuronal injury and apoptosis caused by METH.

  1. Enantioseparation of methamphetamine by supercritical fluid chromatography with cellulose-based packed column.

    Science.gov (United States)

    Segawa, Hiroki; Iwata, Yuko T; Yamamuro, Tadashi; Kuwayama, Kenji; Tsujikawa, Kenji; Kanamori, Tatsuyuki; Inoue, Hiroyuki

    2017-02-04

    The enantiomers of methamphetamine were differentiated by supercritical fluid chromatography (SFC) with an enantioselective cellulose-based packed column. The optimization of the chromatographic conditions was achieved by changing column temperature, co-solvent proportion, additive concentration, flow rate and back pressure. In particular, the additive concentration crucially changed the resolution between the enantiomers. After determining the optimized conditions, the enantiomers of methamphetamine were successfully separated. The analytical precision, accuracy and limit of detection were checked by using the authentic standard and seized real samples. We believe that chiral SFC is a promising method for enantioseparation of forensic samples.

  2. Protective effect of alpha-synuclein knockdown on methamphetamine-induced neurotoxicity in dopaminergic neurons

    OpenAIRE

    Tai, Yunchun; Chen, Ling; Huang, Enping; Liu, Chao; Yang, Xingyi; Qiu, Pingming; Wang, Huijun

    2014-01-01

    The over-expression of α-synuclein is a major factor in the death of dopaminergic neurons in a methamphetamine-induced model of Parkinson's disease. In the present study, α-synuclein knockdown rats were created by injecting α-synuclein-shRNA lentivirus stereotaxically into the right striatum of experimental rats. At 2 weeks post-injection, the rats were injected intraperitoneally with methamphetamine to establish the model of Parkinson's disease. Expression of α-synuclein mRNA and protein in ...

  3. Development of an automated data processing method for sample to sample comparison of seized methamphetamines.

    Science.gov (United States)

    Choe, Sanggil; Lee, Jaesin; Choi, Hyeyoung; Park, Yujin; Lee, Heesang; Pyo, Jaesung; Jo, Jiyeong; Park, Yonghoon; Choi, Hwakyung; Kim, Suncheun

    2012-11-30

    The information about the sources of supply, trafficking routes, distribution patterns and conspiracy links can be obtained from methamphetamine profiling. The precursor and synthetic method for the clandestine manufacture can be estimated from the analysis of minor impurities contained in methamphetamine. Also, the similarity between samples can be evaluated using the peaks that appear in chromatograms. In South Korea, methamphetamine was the most popular drug but the total seized amount of methamphetamine whole through the country was very small. Therefore, it would be more important to find the links between samples than the other uses of methamphetamine profiling. Many Asian countries including Japan and South Korea have been using the method developed by National Research Institute of Police Science of Japan. The method used gas chromatography-flame ionization detector (GC-FID), DB-5 column and four internal standards. It was developed to increase the amount of impurities and minimize the amount of methamphetamine. After GC-FID analysis, the raw data have to be processed. The data processing steps are very complex and require a lot of time and effort. In this study, Microsoft Visual Basic Application (VBA) modules were developed to handle these data processing steps. This module collected the results from the data into an Excel file and then corrected the retention time shift and response deviation generated from the sample preparation and instruments analysis. The developed modules were tested for their performance using 10 samples from 5 different cases. The processed results were analyzed with Pearson correlation coefficient for similarity assessment and the correlation coefficient of the two samples from the same case was more than 0.99. When the modules were applied to 131 seized methamphetamine samples, four samples from two different cases were found to have the common origin and the chromatograms of the four samples were appeared visually identical

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  5. 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...

  6. The Proposed Blended-MDA for Software Modeling in Architecture Phase

    Directory of Open Access Journals (Sweden)

    Sidra Sultana

    2016-08-01

    Full Text Available The Model Driven Architecture is the modeling approach that ensures the re-usability, portability and inter-operability of the software. For the structuring of the system it provides basic guidelines to be modeled. Separating the architecture from the design is one of the main aim of MDA. Functional requirements of the system are being analyzed by the detailed design of the system (for instance, use cases and for non-functional requirements, the infrastructure is provided by the architecture of the software ensuring performance, reliability, scalability etc. In this research paper, some case studies are extensively analyzed in the domain of web applications. Functional and non-functional aspects are analyzed in the comparative analysis table. Finally, the Blended-MDA Framework is proposed for the case study entitled as Online Event Manager.

  7. Both RIG-I and MDA5 detect alphavirus replication in concentration-dependent mode.

    Science.gov (United States)

    Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I

    2016-01-01

    Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus-host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellular pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5.

  8. MDA-based ATL transformation to generate MVC 2 web models

    CERN Document Server

    Rahmouni, M'hamed

    2011-01-01

    Development and maintenance of Web application is still a complex and error-prone process. We need integrated techniques and tool support for automated generation of Web systems and a ready prescription for easy maintenance. The MDA approach proposes an architecture taking into account the development and maintenance of large and complex software. In this paper, we apply MDA approach for generating PSM from UML design to MVC 2Web implementation. That is why we have developed two meta-models handling UML class diagrams and MVC 2 Web applications, then we have to set up transformation rules. These last are expressed in ATL language. To specify the transformation rules (especially CRUD methods) we used a UML profiles. To clearly illustrate the result generated by this transformation, we converted the XMI file generated in an EMF (Eclipse Modeling Framework) model.

  9. MDA-BASED ATL TRANSFORMATION TO GENERATE MVC 2 WEB MODELS

    Directory of Open Access Journals (Sweden)

    Samir Mbarki

    2011-09-01

    Full Text Available Development and maintenance of Web application is still a complex and error-prone process. We need integrated techniques and tool support for automated generation of Web systems and a ready prescription for easy maintenance. The MDA approach proposes an architecture taking into account the development and maintenance of large and complex software. In this paper, we apply MDA approach for generating PSM from UML design to MVC 2Web implementation. That is why we have developed two meta-models handling UML class diagrams and MVC 2 Web applications, then we have to set up transformation rules. These last are expressed in ATL language. To specify the transformation rules (especially CRUD methods we used a UML profiles. To clearly illustrate the result generated by this transformation, weconverted the XMI file generated in an EMF (Eclipse Modeling Framework model.

  10. OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

    Directory of Open Access Journals (Sweden)

    Muñiz P

    2014-05-01

    Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

  11. Methamphetamine use and correlates in two villages of the highland ethnic Karen minority in northern Thailand: a cross sectional study

    Directory of Open Access Journals (Sweden)

    Ono-Kihara Masako

    2009-05-01

    Full Text Available Abstract Background The prevalence of methamphetamine use and human immunodeficiency virus (HIV incidence are high in lowland Thai society. Despite increasing social and cultural mixing among residents of highland and lowland Thai societies, however, little is known about methamphetamine use among ethnic minority villagers in the highlands. Methods A cross-sectional survey examined Karen villagers from a developed and a less-developed village on February 24 and March 26, 2003 to evaluate the prevalence and social correlates of methamphetamine use in northern Thailand. Data were collected in face-to-face interviews using a structured questionnaire. Results The response rate was 79.3% (n = 548. In all, 9.9% (males 17.6%, females 1.7% of villagers reported methamphetamine use in the previous year. Methamphetamine was used mostly by males and was significantly related to primary or lower education; to ever having worked in town; to having used opium, marijuana, or heroin in the past year; and to ever having been diagnosed with a sexually transmitted infection (STI. Conclusion Since labor migration to towns is increasingly common among ethnic minorities, the prevention of methamphetamine use and of HIV/STI infection among methamphetamine users should be prioritized to prevent HIV in this minority population in Thailand.

  12. Functional impairment of the frontal lobe in methamphetamine dependent patients detected on FDG-PET and WCST

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yang Tae; Kwon, Do Hoon [Bugok National Hostipal, Changnyeong (Korea, Republic of); Lee, Sang Woo; Seo, Ji Hyoung; Kang, Seong Min; Lee, Jae Tae; Lee, Kyu Bo [Kyungpook National University Hospital, Daeug (Korea, Republic of)

    2007-07-01

    There are mounting evidences from neuropsychological and neuroimaging studies to support the view that patients with substance dependence have abnormalities in prefrontal cortex. However, functional deficits in prefrontal cortex has not been adequately studied in methamphetamine dependence. Therefore, the purpose of this study is to examine whether methamphetamine dependent patients have metabolic abnormalities and executive dysfunction. Twenty-one abstinent methamphetamine dependent patients who were hospitalized in Bugok National Hospital underwent resting FDG-PET, after which they completed computerized versions of the Wisconsin Card Sorting Test (WCST). Brain PET images were obtained 30 minutes after intravenous injection of 370 MBq of 18F-FDG. Significant differences of glucose metabolism were estimated for every voxel using t-statistics on SPM2 implemented in Matlab between methamphetamine dependent patients and age-matched normal controls. FDG-PET revealed significant hypometabolism in the left inferior frontal white matter (Talairach coordinates (x, y, z): -34, 7, 31) in methamphetamine dependent patients compared to the normal controls (uncorrect p<0.001, t>3.39). The nearest gray matter region was the left inferior frontal cortex (Brodmann area 9). Methamphetamine dependent patients completed significantly fewer categories (3.662.19) and made more perseveration errors (22.0411.94) and total errors (44.5719.70) on the WCST compared to the normal controls (p<0.01). These data suggest that patients with methamphetamine dependence have functional impairments in prefrontal cortex.

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

    Science.gov (United States)

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

    2015-11-01

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

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

    OpenAIRE

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

    2013-01-01

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

  15. Frankincense derived heavy terpene cocktail boosting breast cancer cell(MDA-MB-231) death in vitro简

    Institute of Scientific and Technical Information of China (English)

    Faruck; Lukmanul; Hakkim; Mohammed; Al-Buloshi; Jamal; Al-Sabahi

    2015-01-01

    Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  16. Frankincense derived heavy terpene cocktail boosting breast cancer cell (MDA-MB-231) deathin vitro

    Institute of Scientific and Technical Information of China (English)

    Faruck Lukmanul Hakkim; Mohammed Al-Buloshi; Jamal Al-Sabahi

    2015-01-01

    Objective:To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells (MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis. Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer.MDA-MB-231 cells were treated with different dilutions (1:1 000, 1:1 500, 1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured byMTT assay. Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such asα-pinene (61.56%),α-amyrin (20.6%),β-amyrin (8.1%),β-phellandrene (1.47%) and camphene (1.04%). Heavy terpene cocktail induced significantMDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicityon MDA-MB-231cells compared to hydro distillated essential oil derived from frankincense resin. Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Ourin vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft modelin vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  17. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Science.gov (United States)

    Hall, Duane D; Wu, Yuejin; Domann, Frederick E; Spitz, Douglas R; Anderson, Mark E

    2014-01-01

    Calcium uptake through the mitochondrial Ca2+ uniporter (MCU) is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and prostate cancers and

  18. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Directory of Open Access Journals (Sweden)

    Duane D Hall

    Full Text Available Calcium uptake through the mitochondrial Ca2+ uniporter (MCU is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and

  19. Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2.

    Science.gov (United States)

    Liniger, Matthias; Summerfield, Artur; Zimmer, Gert; McCullough, Kenneth C; Ruggli, Nicolas

    2012-01-01

    Avian influenza viruses (AIV) raise worldwide veterinary and public health concerns due to their potential for zoonotic transmission. While infection with highly pathogenic AIV results in high mortality in chickens, this is not necessarily the case in wild birds and ducks. It is known that innate immune factors can contribute to the outcome of infection. In this context, retinoic acid-inducible gene I (RIG-I) is the main cytosolic pattern recognition receptor known for detecting influenza A virus infection in mammalian cells. Chickens, unlike ducks, lack RIG-I, yet chicken cells do produce type I interferon (IFN) in response to AIV infection. Consequently, we sought to identify the cytosolic recognition elements in chicken cells. Chicken mRNA encoding the putative chicken analogs of CARDIF and LGP2 (chCARDIF and chLGP2, respectively) were identified. HT7-tagged chCARDIF was observed to associate with mitochondria in chicken DF-1 fibroblasts. The exogenous expression of chCARDIF, as well as of the caspase activation and recruitment domains (CARDs) of the chicken melanoma differentiation-associated protein 5 (chMDA5), strongly activated the chicken IFN-β (chIFN-β) promoter. The silencing of chMDA5, chCARDIF, and chIRF3 reduced chIFN-β levels induced by AIV, indicating their involvement in AIV sensing. As with mammalian cells, chLGP2 had opposing effects. While overexpression decreased the activation of the chIFN-β promoter, the silencing of endogenous chLGP2 reduced chIFN-β induced by AIV. We finally demonstrate that the chMDA5 signaling pathway is inhibited by the viral nonstructural protein 1. In conclusion, chicken cells, including DF-1 fibroblasts and HD-11 macrophage-like cells, employ chMDA5 for sensing AIV.

  20. Effect of the environmental enrichment on the severity of psychological dependence and voluntary methamphetamine consumption in methamphetamine withdrawn rats.

    Science.gov (United States)

    Hajheidari, Samira; Miladi-Gorji, Hossein; Bigdeli, Imanollah

    2015-01-01

    Previously results have been shown that chronic methamphetamine causes dependence, withdrawal syndrome and drug craving. Also, environmental enrichment (EE) has been shown protective effects in several animal models of addiction. This study evaluated effect of the EE on the anxiety-depression profile and voluntary METH consumption in METH-dependent rats after abstinence. The rats were chronically treated with bi-daily doses (2 mg/kg, at 12 h intervals) of METH over a period of 14 days. METH dependent rats reared in standard environment (SE) or EE during spontaneous METH withdrawal which lasted 30 days. Then, the rats were tested for anxiety (the elevated plus maze-EPM) and depression (forced swim test-FST) and also voluntary consumption of METH using a two-bottle choice paradigm (TBC). The results showed that the EE rats exhibited an increase in EPM open arm time and entries (P Environmental enrichment seems to be one of the strategies in reduction of behavioral deficits and the risk of relapse induced by METH withdrawal.