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Monitoring of amphetamine-type stimulant (ATS) confronts clinical labs with a high number of samples involving a variety of biological matrices. Liquid chromatography-tandem mass spectrometry (LC-MS/MS), routinely used for confirmation of ATS abuse, requires of laborious and matrix-dependent sample treatment methods, this increasing analysis time and cost. In this work, a universal and single-step sample treatment, based on supramolecular solvents (SUPRAS), was proposed for simplifying ATS confirmation in seven biological matrices. The SUPRAS was synthesized in situ in the sample (900 µL of basified oral fluid, urine, serum, sweat or breast milk or 50 mg of digested hair or fingernails) by the addition of hexanol (200 µL) and tetrahydrofuran (900 µL). The mixture was vortex-shaken and centrifuged and the SUPRAS extract was subsequently analyzed by positive ion mode electrospray LC-MS/MS. The method was fully validated for amphetamine (AMP), methamphetamine (MA), 3,4-methylenedioxyamphetamine (MDA), N-ethyl-3,4-methylenedioxyamphetamine (MDEA) and N-methyl-3,4-methylenedioxyamphetamine (MDMA). Maximum ion suppression or enhancement was 9% and 7%, respectively, and extraction recoveries (87-111%) and within- (0.1-6.7%) and between-day (0.3-9.7%) CVs were all within required values. The lower limits of quantification (LLOQ) for biological fluids (5 ng/mL), and hair and fingernails (100 ng/g) were all well below the cut-offs established by worldwide organizations. Confirmation of MDA was carried out in five urine samples that tested positive for ATS by immunoassay. The SUPRAS-LC-MS/MS methodology succeeded in developing a hitherto unexplored and universal tool for quantifying ATS in a comprehensive pool of biological matrices of interest in forensic and clinical samples.

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In the absence of overt cellular pathology but profound perceptual disorganization and cognitive deficits, schizophrenia is increasingly considered a disorder of neural coordination. Thus, different causal factors can similarly interrupt the dynamic function of neuronal ensembles and networks, in particular in the prefrontal cortex (PFC), leading to behavioral disorganization. The importance of establishing preclinical biomarkers for this aberrant function has prompted investigations into the nature of psychotomimetic drug effects on PFC neuronal activity. The drugs used in this context include serotonergic hallucinogens, amphetamine, and NMDA receptor antagonists. A prominent line of thinking is that these drugs create psychotomimetic states by similarly disinhibiting the activity of PFC pyramidal neurons. In the present study we did not find evidence in support of this mechanism in PFC subregions of freely moving rats. Whereas the NMDA receptor antagonist MK801 increased PFC population activity, the serotonergic hallucinogen DOI dose-dependently decreased population activity. Amphetamine did not strongly affect this measure. Despite different effects on the direction of change in activity, all three drugs caused similar net disruptions of population activity and modulated gamma oscillations. We also observed reduced correlations between spike-rate and local field potential power selectively in the gamma band suggesting that these drugs disconnect spike-discharge from PFC gamma oscillators. Gamma band oscillations support cognitive functions affected in schizophrenia. These findings provide insight into mechanisms that may lead to cortical processing deficits in schizophrenia and provide a novel electrophysiological approach for phenotypic characterization of animal models of this disease.

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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.

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Under this Final Rule, the Drug Enforcement Administration (DEA) is updating the Table of Excluded Nonnarcotic Products found in 21 CFR 1308.22 to include the Nasal Decongestant Inhaler/Vapor Inhaler (containing 50 mg Levmetamfetamine) manufactured by Classic Pharmaceuticals, LLC and marketed under various private labels (to include the "Premier Value" and "Kroger" labels). This nonnarcotic drug product, which may be lawfully sold over the counter without a prescription under the Federal Food, Drug, and Cosmetic Act, is excluded from provisions of the Controlled Substances Act (CSA) pursuant to 21 U.S.C. 811(g)(1).

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MDMA ("Ecstasy") and its analogues such as MDE and MDA are amphetamine derivatives reported to produce an altered state with emotional overtones. Since more than ten years, ecstasy is after cannabis the most frequently used recreational drug by young adults, particularly in the so-called techno-scene. However, according to a recent survey there is an increasing trend for a revival of classic amphetamine and hallucinogen abuse, possibly due to the concern about the potential neurotoxicity and somatic risks associated with ecstasy use. Of the hallucinogens consumed, psilocybin containing mushroom ("magic mushrooms"), but also LSD are at the forefront. The present contribution summarizes the psychological and somatic effects of hallucinogens, amphetamines, and entactogens.

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Experiments were conducted to compare the effects of 4-ethoxyamphetamine, a novel "designer" amphetamine, with (+)-amphetamine and an earlier "designer" amphetamine, 4-methoxyamphetamine, on rats. (+)-Amphetamine significantly decreased frequency threshold measures in an intracranial self-stimulation (ICSS) procedure using medial forebrain bundle electrodes, while 4-methoxyamphetamine and 4-ethoxyamphetamine increased these ICSS frequency thresholds. 4-Methoxyamphetamine and 4-ethoxyamphetamine had more potent effects on inhibition of uptake and stimulation of spontaneous release of 5-hydroxytryptamine (serotonin) than of dopamine. It is concluded that the neuropsychopharmacological profile of 4-ethoxyamphetamine is unlike that of (+)-amphetamine, but similar to that of 4-methoxyamphetamine, a potent hallucinogen in humans.

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The infrared (IR) spectra of 15 drugs of abuse were analyzed for similarity by using techniques of numerical taxonomy. The study included six barbiturates (amobarbital, barbital, butabarbital, phentobarbital, phenobarbital, and secobarbital), four amphetamine-related compounds (amphetamine, ephedrine, methamphetamine, and phentermine), and five other drugs (cocaine, heroin, phencyclidine, phendimetrazine, and diazepam). Three character sets were based on increasing numbers (10, 24, and 36) of IR peaks. The cluster analysis, principal component analysis, and nonmetric multidimensional scaling elements of the program system NT-SYS were used to structure taxonomic distances between drugs. Best results were obtained from the 36-peak data set; ordination diagrams proved to be more visually informative than phenograms. Preliminary results from our analysis of this set of drugs indicate that an expanded multivariate approach to drug classification may be useful.

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