Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation
| العنوان: | Dose-response pharmacological study of mephedrone and its metabolites: pharmacokinetics, serotoninergic effects, and impact of CYP2D6 genetic variation |
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| المؤلفون: | Marta Torrens, Magí Farré, Oscar J. Pozo, Marcel·li Carbó, Samanta Yubero-Lahoz, Rafael de la Torre, Esther Papaseit, Clara Pérez-Mañá, Eulàlia Olesti, Mitona Pujadas |
| المصدر: | CLINICAL PHARMACOLOGY & THERAPEUTICS r-IGTP. Repositorio Institucional de Producción Científica del Instituto de Investigación Germans Trias i Pujol instname Recercat. Dipósit de la Recerca de Catalunya |
| بيانات النشر: | Wiley, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | CYP2D6, Serotonin, Medicaments -- Toxicologia, Metabolic Clearance Rate, Phases of clinical research, Pharmacology, 030226 pharmacology & pharmacy, digestive system, Methamphetamine, 03 medical and health sciences, 0302 clinical medicine, Mephedrone, Pharmacokinetics, Genetic variation, medicine, Humans, Pharmacology (medical), skin and connective tissue diseases, Cross-Over Studies, Dose-Response Relationship, Drug, business.industry, Illicit Drugs, Acute toxicity, Medicaments -- Administració, Phenotype, Cytochrome P-450 CYP2D6, 030220 oncology & carcinogenesis, Area Under Curve, business, Serotonin Effects, medicine.drug |
| الوصف: | Mephedrone (MEPH), the most widely consumed synthetic cathinone, has been associated with acute toxicity episodes. The aim of this report was to study its metabolic disposition and the impact of genetic variation of CYP2D6 on MEPH metabolism, in a dose range compatible with its recreational use. A randomized, crossover, phase I clinical trial was performed. Subjects received 50 and 100 mg (n = 3) and 150 and 200 mg (n = 6) of mephedrone and were genetically and phenotypically characterized for the CYP2D6 allelic variation. Our results showed a linear kinetics of mephedrone at the dose range assayed: plasma concentrations, cardiovascular and subjective effects, and blood serotonin concentrations all correlated in a dose-dependent manner. Mephedrone metabolic disposition is mediated by CYP2D6. Mephedrone pharmacology presented a linear dose-dependence within the range of doses tested. The metabolism of mephedrone by CYP2D6 implies that recreational users with no or low CYP2D6 functionality are exposed to unwanted acute toxicity episodes. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0009-9236 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6b7340a5d782e79f231ea89802bcee5Test http://hdl.handle.net/10230/43021Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d6b7340a5d782e79f231ea89802bcee5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00099236 |
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