Three review articles were published this period. One research paper was published. This paper reported: """"""""Based on animal data, there is speculation that (+ or -)-3,4-methylenedioxymethamphetamine (MDMA) is neurotoxic to humans. Extrapolation of MDMA findings from animals to humans requires assessment of pharmacokinetics in various species, and low-dose administration data from rats are lacking. In this study, we examine MDMA pharmacokinetics in rats given low (2 mg/kg) and high (10 mg/kg) doses of racemic MDMA via intraperitoneal, subcutaneous, and oral routes. Repeated blood specimens were collected from venous catheters, and plasma was assayed for MDMA and its metabolites, 4-hydroxy-3-methoxymethamphetamine (HMMA) and 3,4-methylenedioxyamphetamine (MDA), by gas chromatography-mass spectrometry. After 2 mg/kg, maximum MDMA concentrations (C(max)) were approximately 200 ng/ml for intraperitoneal and subcutaneous routes, but less for the oral route. MDMA plasma half-lives were <1 h for low-dose groups, whereas HMMA and MDA half-lives were >2 h. After 10 mg/kg, MDMA areas under the curve (AUCs) were 21-fold (intraperitoneal), 10-fold (subcutaneous), and 36-fold (oral) greater than those at 2 mg/kg. In contrast, HMMA AUC values in high-dose groups were <3-fold above those at 2 mg/kg. Several new findings emerge from this report of low-dose MDMA pharmacokinetics in rats. First, 2 mg/kg MDMA in rats can produce MDMA C(max) values similar to those in humans, perhaps explaining why both species discriminate 1.5 mg/kg MDMA in laboratory paradigms. Second, our data provide additional support for nonlinear kinetics of MDMA in rats, and, analogous to humans, this phenomenon appears to involve impaired drug metabolism. Finally, given key similarities between MDMA pharmacokinetics in rats and humans, data from rats may be clinically relevant when appropriate dosing conditions are used.""""""""

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2010
Total Cost
$194,936
Indirect Cost
Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
Zip Code
Baumann, Michael H; Majumdar, Susruta; Le Rouzic, Valerie et al. (2018) Pharmacological characterization of novel synthetic opioids (NSO) found in the recreational drug marketplace. Neuropharmacology 134:101-107
Prekupec, Matthew P; Mansky, Peter A; Baumann, Michael H (2017) Misuse of Novel Synthetic Opioids: A Deadly New Trend. J Addict Med 11:256-265
Solis Jr, Ernesto; Partilla, John S; Sakloth, Farhana et al. (2017) N-Alkylated Analogs of 4-Methylamphetamine (4-MA) Differentially Affect Monoamine Transporters and Abuse Liability. Neuropsychopharmacology 42:1950-1961
Elmore, Joshua S; Dillon-Carter, Ora; Partilla, John S et al. (2017) Pharmacokinetic Profiles and Pharmacodynamic Effects for Methylone and Its Metabolites in Rats. Neuropsychopharmacology 42:649-660
Hoffman, Alexander F; Lycas, Matthew D; Kaczmarzyk, Jakub R et al. (2017) Disruption of hippocampal synaptic transmission and long-term potentiation by psychoactive synthetic cannabinoid 'Spice' compounds: comparison with ?9 -tetrahydrocannabinol. Addict Biol 22:390-399
Baumann, Michael H; Bukhari, Mohammad O; Lehner, Kurt R et al. (2017) Neuropharmacology of 3,4-Methylenedioxypyrovalerone (MDPV), Its Metabolites, and Related Analogs. Curr Top Behav Neurosci 32:93-117
McLaughlin, Gavin; Morris, Noreen; Kavanagh, Pierce V et al. (2017) Synthesis, characterization and monoamine transporter activity of the new psychoactive substance mexedrone and its N-methoxy positional isomer, N-methoxymephedrone. Drug Test Anal 9:358-368
Shekar, Aparna; Aguilar, Jenny I; Galli, Greta et al. (2017) Atypical dopamine efflux caused by 3,4-methylenedioxypyrovalerone (MDPV) via the human dopamine transporter. J Chem Neuroanat 83-84:69-74
Carlier, Jeremy; Scheidweiler, Karl B; Wohlfarth, Ariane et al. (2016) Quantification of [1-(5-fluoropentyl)-1H-indol-3-yl](naphthalene-1-yl)methanone (AM-2201) and 13 metabolites in human and rat plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr A 1451:97-106
Baumann, Michael H (2016) The Changing Face of Recreational Drug Use. Cerebrum 2016:

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