The Experts below are selected from a list of 92205 Experts worldwide ranked by ideXlab platform
Gwendolyn A Mcmillin - One of the best experts on this subject based on the ideXlab platform.
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cross reactivity of phentermine with an immunoassay designed to detect amphetamine in a meconium specimen
Clinical Chemistry, 2009Co-Authors: Stephanie J Marin, Christine Moore, Gwendolyn A McmillinAbstract:Neonates exposed to drugs of abuse in utero can experience prenatal drug dependence leading to withdrawal symptoms and a number of other health problems (1). Early detection of exposure is critical to guide necessary treatment and improve outcomes for these children. Meconium begins to form in the digestive tract at 12–16 weeks gestation. Drugs and metabolites collect in meconium beginning at about 5 months gestation. Thus, meconium testing can identify exposure to drugs during the last 4 months of a full-term pregnancy (2). Our laboratory uses ELISA reagents (Immunalysis) to detect drugs of abuse in meconium. Poor specificity of immunoassay reagents for Amphetamines is well characterized and as a result, specimens that test positive for Amphetamines by immunoassay are routinely tested by a second analytical method to prevent false-positive results. Our ELISA screen for meconium has separate detection antibodies for amphetamine and methamphetamine. The ELISA cutoff for these drugs is 20 ng/g. All positive screen results are confirmed by GC-MS. We report the investigation of an unconfirmed positive amphetamine result. ELISA assay of the meconium specimen …
Arian Van Asten - One of the best experts on this subject based on the ideXlab platform.
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novel selectivity based forensic toxicological validation of a paper spray mass spectrometry method for the quantitative determination of eight Amphetamines in whole blood
Journal of the American Society for Mass Spectrometry, 2017Co-Authors: Sebastiaan F Teunissen, Patrick W Fedick, Bjorn J A Berendsen, Michel W F Nielen, Marcos N Eberlin, Graham R Cooks, Arian Van AstenAbstract:Paper spray tandem mass spectrometry is used to identify and quantify eight individual Amphetamines in whole blood in 1.3 min. The method has been optimized and fully validated according to forensic toxicology guidelines, for the quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), para-methoxyamphetamine (PMA), para-methoxymethamphetamine (PMMA), and 4-fluoroamphetamine (4-FA). Additionally, a new concept of intrinsic and application-based selectivity is discussed, featuring increased confidence in the power to discriminate the Amphetamines from other chemically similar compounds when applying an ambient mass spectrometric method without chromatographic separation. Accuracy was within ±15% and average precision was better than 15%, and better than 20% at the LLOQ. Detection limits between 15 and 50 ng/mL were obtained using only 12 μL of whole blood. Graphical abstract ᅟ.
Catherine Gebhard - One of the best experts on this subject based on the ideXlab platform.
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Amphetamines induce tissue factor and impair tissue factor pathway inhibitor role of dopamine receptor type 4
European Heart Journal, 2010Co-Authors: Catherine Gebhard, Alexander Breitenstein, Alexander Akhmedov, Giovanni G Camici, Thomas F Luscher, Felix C TannerAbstract:Aims Amphetamine intake is associated with acute vascular syndromes. Since these events are caused by arterial thrombosis and this in turn is triggered by tissue factor (TF), this study examines whether Amphetamines regulate TF in human endothelial cells. Methods and results Amphetamine (10−7–10−4 mol/L) enhanced thrombin- and tumour necrosis factor (TNF)-α-induced as well as basal TF expression ( P = 0.029, 0.0003, and 0.003 at maximal concentration), and TNF-α-induced plasminogen activator inhibitor (PAI)-1 expression ( P = 0.003), whereas tissue factor pathway inhibitor expression was impaired ( P = 0.008). Similarly, 3,4-methylenedioxymethamphetamine (10−7–10−4 mol/L) enhanced TF expression ( P = 0.046). These effects were paralleled by an increased TF activity ( P = 0.002); moreover, clotting time of human plasma was accelerated by supernatant from amphetamine-treated cells ( P = 0.03). Amphetamine enhanced TF mRNA expression via phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) and p38 ( P = 0.03 and 0.033), but not c-Jun NH2-terminal kinase (JNK; P = 0.81). The effect of amphetamine on TF expression was abrogated by the dopamine D4 receptor antagonists L-745,870 and L-750,667, but not D2 or D3 receptor antagonists; furthermore, L-745,870 blunted the amphetamine-induced activation of ERK and p38, but not JNK. Conclusion Amphetamines induce endothelial TF expression via stimulation of dopamine D4 receptor and activation of the MAPKs p38 and ERK. These effects occur at clinically relevant amphetamine concentrations and may account for the increased incidence of acute vascular syndromes after amphetamine consumption.
Janusz Pawliszyn - One of the best experts on this subject based on the ideXlab platform.
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method optimization for the analysis of Amphetamines in urine by solid phase microextraction
Analytical Chemistry, 1997Co-Authors: Heather Lord, Janusz PawliszynAbstract:Solid-phase microextraction is under investigation in many laboratories for its usefulness in the analysis of an ever widening variety of compounds. As new classes of compounds are investigated and new challenges arise, the methods are adapted to accommodate them. Polar semivolatiles are increasingly under study as analytical targets, and difficulties with small partition coefficients and long equilibration times have been identified. Amphetamine and methamphetamine were selected as semivolatiles exhibiting these limitations, and methods to optimize their analyses were investigated. Amphetamines are frequently monitored in very complex matrixes. Headspace methods minimize interactions between the sample and the fiber and have proven useful for these analyses. Several areas of experimental design were considered in the process of method optimization. These included matrix modification by heating, stirring, methanol content, addition of salt, and pH buffering. It was found that these Amphetamines could be r...
Michael Freissmuth - One of the best experts on this subject based on the ideXlab platform.
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Amphetamines new psychoactive drugs and the monoamine transporter cycle
Trends in Pharmacological Sciences, 2015Co-Authors: Harald H. Sitte, Michael FreissmuthAbstract: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.
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ca2 calmodulin dependent protein kinase iiα αcamkii controls the activity of the dopamine transporter implications for angelman syndrome
Journal of Biological Chemistry, 2012Co-Authors: Thomas Steinkellner, Sonja Sucic, Jaewon Yang, Therese Montgomery, Weiqiang Chen, Marietherese Winkler, Gert Lubec, Michael Freissmuth, Ype Elgersma, Harald H. SitteAbstract:Abstract The dopamine transporter (DAT) is a crucial regulator of dopaminergic neurotransmission, controlling the length and brevity of dopaminergic signalling. DAT is also the primary target of psychostimulant drugs, such as cocaine and Amphetamines. Conversely, methylphenidate and amphetamine are both used clinically in the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. The action of Amphetamines, which induce transport reversal, relies primarily on the ionic composition of the intra- and extracellular milieus. Recent findings suggest that DAT interacting proteins may also play a significant role in the modulation of reverse dopamine transport. The pharmacological inhibition of the serine/threonine kinase αCaMKII attenuates amphetamine-triggered DAT-mediated 1-methyl-4-phenylpyridinium (MPP+) efflux. More importantly, αCaMKII has also been shown to bind DAT in vitro and is therefore believed to be an important player within the DAT interactome. Herein, we show that αCaMKII co-immunoprecipitates with DAT in mouse striatal synaptosomes. Mice which lack αCaMKII or which express a permanently self-inhibited αCaMKII (αCaMKIIT305D) exhibit significantly reduced amphetamine-triggered DAT-mediated MPP+ efflux. Additionally, we investigated mice which mimick the neurogenetic disease known as Angelman Syndrome. These mice possess reduced αCaMKII activity. Angelman Syndrome mice demonstrated an impaired DAT efflux function which was comparable to that of the αCaMKII mutant mice, indicating that DAT mediated dopaminergic signalling is affected in Angelman Syndrome.
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Amphetamines take two to tango an oligomer based counter transport model of neurotransmitter transport explores the amphetamine action
Molecular Pharmacology, 2005Co-Authors: Stefan Seidel, Marion Holy, Oliver Kudlacek, Petra Scholze, Ernst A. Singer, Herwig Just, Hesso Farhan, Karl Koppatz, Peter Krivanek, Michael FreissmuthAbstract:Amphetamine congeners [e.g., 3,4-methylenedioxymetamphetamine (MDMA), or "ecstasy"] are substrates for monoamine transporters (i.e., the transporters for serotonin, norepinephrine, and dopamine); however, their in vivo-action relies on their ability to promote monoamine efflux. The mechanistic basis for this counter transport remains enigmatic. We tested the hypothesis that outward transport is contingent on the oligomeric nature of neurotransmitter transporters by creating a concatemer of the serotonin transporter and the amphetamine-resistant GABA transporter. In cells expressing the concatemer, amphetamine analogs promoted GABA efflux and blunted GABA influx. In contrast, the natural substrates serotonin and GABA only cause mutual inhibition of influx via the other transporter moiety in the concatemer. GABA efflux through the concatemer that was promoted by amphetamine analogs was blocked by the protein kinase C inhibitors GF109203X (bisindoylmaleimide I) and Go6983 (2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide). Thus, based on our observations, we propose that, in the presence of amphetamine analogs, monoamine transporters operate as counter-transporters; influx and efflux occur through separate but coupled moieties. Influx and efflux are coupled via changes in the ionic gradients, but these do not suffice to account for the action of Amphetamines; the activity of a protein kinase C isoform provides a second stimulus that primes the inward facing conformation for outward transport.
