Nonlinear Pharmacokinetics of (±)3,4-Methylenedioxymethamphetamine (MDMA) and Its Pharmacodynamic Consequences in the Rat
| Autor: | Gina F. Marrone, Marilyn A. Huestis, Karl B. Scheidweiler, Marta Concheiro, Richard B. Rothman, Michael H. Baumann |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Serotonin N-Methyl-3 4-methylenedioxyamphetamine Cmax Pharmaceutical Science Pharmacology Methamphetamine Rats Sprague-Dawley Pharmacokinetics mental disorders Male rats medicine Animals Adverse effect 3 4-Methylenedioxyamphetamine Chemistry Nonlinear pharmacokinetics MDMA Articles Rats Area Under Curve Pharmacodynamics psychological phenomena and processes medicine.drug |
| Zdroj: | Drug Metabolism and Disposition. 42:119-125 |
| ISSN: | 1521-009X 0090-9556 |
| DOI: | 10.1124/dmd.113.053678 |
| Popis: | 3,4-Methylenedioxymethamphetamine (MDMA) is a widely abused illicit drug that can cause severe and even fatal adverse effects. However, interest remains for its possible clinical applications in posttraumatic stress disorder and anxiety treatment. Preclinical studies to determine MDMA’s safety are needed. We evaluated MDMA’s pharmacokinetics and metabolism in male rats receiving 2.5, 5, and 10 mg/kg s.c. MDMA, and the associated pharmacodynamic consequences. Blood was collected via jugular catheter at 0, 0.5, 1, 2, 4, 6, 8, 16, and 24 hours, with simultaneous serotonin (5-HT) behavioral syndrome and core temperature monitoring. Plasma specimens were analyzed for MDMA and the metabolites (±)-3,4-dihydroxymethamphetamine (HHMA), (±)-4-hydroxy-3-methoxymethamphetamine (HMMA), and (±)-3,4-methylenedioxyamphetamine (MDA) by liquid chromatography–tandem mass spectrometry. After 2.5 mg/kg MDMA, mean MDMA Cmax was 164 ± 47.1 ng/ml, HHMA and HMMA were major metabolites, and |
| Databáze: | OpenAIRE |
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