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Amphetamine Derivatives (amphetamine + derivative)
Selected AbstractsBRIEF REPORT: Increased blood oxidative stress in amphetamine usersADDICTION BIOLOGY, Issue 1 2010Piyarat Govitrapong ABSTRACT Amphetamine derivatives have been shown to be a potential brain neurotoxin based on the production of free radicals that occurs after administration. The purpose of this study was to examine the lipid peroxidation and antioxidant enzymes in the blood of amphetamine users. The plasma lipid peroxidation was determined and reported as thiobarbituric acid reactive substance and was significantly increased (+21%), whereas the activities of the erythrocyte antioxidant enzymes glutathione peroxidase, catalase, and superoxide dismutase were significantly decreased (,32%, ,14% and ,31%, respectively) in amphetamine users. These results implicated the potential role of oxidative stress in amphetamine-induced neurotoxicity. [source] Methylenedioxymethamphetamine (MDMA, ,Ecstasy'): a stressor on the immune systemIMMUNOLOGY, Issue 4 2004Thomas J. Connor Summary Drug abuse is a global problem of considerable concern to health. One such health concern stems from the fact that many drugs of abuse have immunosuppressive actions and consequently have the potential to increase susceptibility to infectious disease. This article is focused on the impact of the amphetamine derivative, methylenedioxymethamphetamine (MDMA; ,Ecstasy') on immunity. Research conducted over the last 5 years, in both laboratory animals and humans, has demonstrated that MDMA has immunosuppressive actions. Specifically, MDMA suppresses neutrophil phagocytosis, suppresses production of the pro-inflammatory cytokines tumour necrosis factor-, (TNF-,) and interleukin (IL)-1,, and increases production of the endogenous immunosuppressive cytokine (IL-10), thereby promoting an immunosuppressive cytokine phenotype. MDMA also suppresses circulating lymphocyte numbers, with CD4+ T cells being particularly affected, and alters T-cell function as indicated by reduced mitogen-stimulated T-cell proliferation, and a skewing of T-cell cytokine production in a T helper 2 (Th2) direction. For the most part, the aforementioned effects of MDMA are not the result of a direct action of the drug on immune cells, but rather caused by the release of endogenous immunomodulatory substances. Consequently, the physiological mechanisms that are thought to underlie the immunosuppressive effects of MDMA will be discussed. As many of the physiological changes elicited by MDMA closely resemble those induced by acute stress, it is suggested that exposure to MDMA could be regarded as a ,chemical stressor' on the immune system. Finally, the potential of MDMA-induced immunosuppression to translate into significant health risks for abusers of the drug will be discussed. [source] Delayed pre-conditioning by 3-nitropropionic acid prevents 3,4-methylenedioxymetamphetamine-induced 5-HT deficitsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Elena Puerta J. Neurochem. (2010) 114, 843,852. Abstract The aim of the present study was to investigate whether late pre-conditioning using 3-nitropropionic acid (3NP) prevents the 5-hydroxytryptamine (5-HT) deficits caused by the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) in the rat. For this purpose we administered 3NP 24 h before MDMA (3 × 5 mg/kg i.p., every 2 h) and rats were killed 7 days later. Pre-treatment of 3NP afforded complete protection against MDMA-induced 5-HT deficits independent of any effect on MDMA-induced hyperthermia or 5-HT transporter activity. To identify the transductional mechanisms responsible for the neuroprotective effect of 3NP, we first examined the involvement of nitric oxide (NO) by using selective inhibitors of all three nitric oxide synthase isoforms. Inhibition of endothelial and neuronal nitric oxide synthase, but not inducible nitric oxide synthase, reversed 3NP-induced pre-conditioning. The NO donor S -Nitroso- N -acetylpenicilamine mimicked 3NP effects further suggesting the involvement of NO in mediating 3NP protection. To investigate the involvement of NOS/soluble guanylate cyclase (sGC)/protein kinase G/mitochondrial ATP-sensitive potassium channels (mitoKATP) signaling pathway we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, and 1H -(1,2,4)oxadiazolo[4,3- a]quinoxaline-1-one, a potent inhibitor of sGC, on 3NP-induced tolerance. 5-hydroxydecanoate, but not 1H -(1,2,4)oxadiazolo[4,3- a]quinoxaline-1-one, suppressed 3NP-mediated protection suggesting that mitoKATP opening, but not NO-mediated activation of sGC, participates in the mechanism underlying tolerance to MDMA. Our data also showed that the protective effect of 3NP was abolished by cycloheximide, supporting the involvement of de novo protein synthesis. In conclusion, 3NP-induced delayed tolerance against 5-HT deficits caused by MDMA occurs via NO production. [source] Poly(methacrylic acid-ethylene glycol dimethacrylate) monolith in-tube solid-phase microextraction applied to simultaneous analysis of some amphetamine derivatives in urine by capillary zone electrophoresisELECTROPHORESIS, Issue 16 2005Fang Wei Abstract A method based on in-tube solid-phase microextraction and capillary zone electrophoresis (CZE) was proposed for simultaneously determining four amphetamines (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxymethamphetamine) in urine. A poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column, which can provide sufficient extraction efficiency, was introduced for the extraction of amphetamines from urine samples. The hydrophobic main chains and acidic pendant groups of the monolithic column make it a superior material for extraction of basic analytes from aqueous matrix. After extraction, the samples were analyzed by CZE. The best separation was achieved using a buffer composed of 0.1,M disodium hydrogen phosphate (adjusted to pH,4.5 with 1,M hydrochloric acid) and 20% methanol v/v, with a temperature and voltage of 25°C and 20,kV, respectively. By applying electrokinetic injection with field-amplified sample stacking, detection limits of 25,34,µg/L were achieved. Excellent method of reproducibility was found over a linear range of 0.1,5,mg/L. Determination of these analytes from abusers' urine sample was also demonstrated. [source] N,N -dimethyl-thioamphetamine and methyl-thioamphetamine, two non-neurotoxic substrates of 5-HT transporters, have scant in vitro efficacy for the induction of transporter-mediated 5-HT release and currentsJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Marco Gobbi Abstract We studied two non-neurotoxic amphetamine derivatives (methyl-thioamphetamine, MTA and N,N- dimethylMTA, DMMTA) interacting with serotonin (5-HT) transporters (SERTs) with affinities comparable to that of p- Cl-amphetamine (pCA). The rank order for their maximal effects in inducing both [3H]5-HT release from rat brain synaptosomes or hSERT-expressing HEK-293 cells, and currents in hSERT-expressing oocytes, was pCA » MTA , DMMTA. A correlation between drug-induced release and currents is also strengthened by the similar bell shape of the dose,response curves. Release experiments indicated that MTA and DMMTA are SERT substrates although MTA is taken up by HEK-293 cells with a Vmax 40% lower than pCA. The weak effects of MTA and DMMTA in vitro might therefore be due to their properties as ,partial substrates' on the mechanisms, other than translocation, responsible for currents and/or release. After either local or systemic in vivo administration, MTA and DMMTA release 5-HT in a manner comparable to pCA. These findings confirm that the neurotoxic properties of some amphetamine derivatives are independent of their 5-HT-releasing activity in vivo. It is worth noting that only those amphetamine derivatives with high efficiency in inducing 5-HT release and currents in vitro have neurotoxic properties. [source] Paramethoxyamphetamine (PMA) poisoning; a ,party drug' with lethal effectsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2003S. Refstad Among young people in Norway the recreational use of amphetamine derivatives seems to be increasing. Methylenedioxymethamphetamine (MDMA), known as ecstasy, is the dominant substance, having both stimulant and psychedelic properties. Depending on the illegal source of these so-called ,party drugs' the content and purity can vary. This case report describes the first lethal case of paramethoxyamphetamine (PMA) and paramethoxymethamphetamine (PMMA) intoxication reported in Norway. A 16-year-old male was admitted to a local hospital in a coma with seizures and hyperthermia after he had been found undressed and barefooted in a local forest (temperature 2°C). He was intubated and given supportive care. Blood chemistry revealed hypoglycaemia, hypocalcaemia and hyperkalaemia. Shortly after transfer to the central hospital he developed bradycardia with continuous seizures and asystole. Adverse effects of MDMA are well described and include serotonergic and sympathomimetic symptoms with hyperthermia, coagulopathy, rhabdomyolysis and acute kidney and liver failure. Case reports of PMA deaths collectively suggest PMA to be more toxic than MDMA. A delayed effect after intake of PMA compared with MDMA can lead to increased intake. Hypoglycaemia and hyperkalaemia may be specific to PMA poisoning. Increased thermo genesis will result in a search for cooling, which explains the attempt to undress and a desire to submerge in water. In a cool climate this behaviour itself can be lethal. Measures to treat seizures, hypoglycaemia, electrolyte anomalies and hyperthermia are the therapeutic goals. No specific treatment is available. [source] Multi-residue analysis of eight thioamphetamine designer drugs in human urine by liquid chromatography/tandem mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2009Maria Nieddu An analytical procedure for the simultaneous determination in human urine of several thioamphetamine designer drugs (2C-T and ALEPH series) is reported. The quantitative analysis was performed by liquid chromatography/tandem mass spectrometry and has been fully validated. The mass spectrometer was operated in positive-ion, selected reaction monitoring (SRM) mode. In order to minimize interferences with matrix components and to preconcentrate target analytes, solid-phase extraction was introduced in the method as a clean-up step. The entire method was validated for selectivity, linearity, precision and accuracy. The method turned out to be specific, sensitive, and reliable for the analysis of amphetamine derivatives in urine samples. The calibration curves were linear over the concentration range of 1 to 100,ng,mL,1 for all drugs with correlation coefficients that exceeded 0.996. The lower limits of detection (LODs) and quantification (LOQs) ranged from 1.2 to 4.9,ng,mL,1 and from 3.2 to 9.6,ng,mL,1, respectively. Copyright © 2009 John Wiley & Sons, Ltd. [source] Fast chiral separation of drugs using columns packed with sub-2 ,m particles and ultra-high pressureCHIRALITY, Issue 3 2010Davy Guillarme Abstract The use of columns packed with sub-2 ,m particles in liquid chromatography with very high pressure conditions (known as UHPLC) was investigated for the fast enantioseparation of drugs. Two different procedures were evaluated and compared using amphetamine derivatives and ,-blockers as model compounds. In one case, cyclodextrins (CD) were directly added to the mobile phase and chiral separations were carried out in less than 5 min. However, this strategy suffered from several drawbacks linked to column lifetime and low chromatographic efficiencies. In the other case, the analysis of enantiomers was carried out after a derivatization procedure using two different reagents, 2,3,4-tri-O-acetyl-,- D -arabinopyranosyl isothiocyanate (AITC) and N -,-(2,4-dinitro-5-fluorophenyl)- L -alaninamide (Marfey's reagent). Separation of several amphetamine derivatives contained within the same sample was achieved in 2,5 min with high efficiency and selectivity. The proposed approach was also successfully applied to the enantiomeric purity determination of (+)-(S)-amphetamine and (+)-(S)-methamphetamine. Similar results were obtained with ,-blockers, and the separation of 10 enantiomers was carried out in less than 3 min, whereas the individual separation of several ,-blocker enantiomers was performed in 1 min or less. Chirality, 2010. © 2009 Wiley-Liss, Inc. [source] | ||||||||||||||||