Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/47623
Title: An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
Author: López-Arnau, Raúl
Martínez-Clemente, José
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Escubedo Rafa, Elena
Camarasa García, Jordi
Keywords: Amfetamines
Farmacocinètica
Rates (Animals de laboratori)
Locomoció animal
Amphetamines
Pharmacokinetics
Rats as laboratory animals
Animal locomotion
Issue Date: 1-Aug-2013
Publisher: Elsevier B.V.
Abstract: Material and methods. Methylone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (15 and 30 mg/kg). Plasma concentrations and metabolites were characterized by LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results. Oral administration of methylone induced a dose-dependent increase in locomotor activity in rats. The plasma concentrations after i.v. administration were described by a two-compartment model with distribution and terminal elimination phases of α = 1.95 h− 1 and β = 0.72 h− 1. For oral administration, peak methylone concentrations were achieved between 0.5 and 1 h and fitted to a flip-flop model. Absolute bioavailability was about 80% and the percentage of methylone protein binding was of 30%. A relationship between methylone brain levels and free plasma concentration yielded a ratio of 1.42 ± 0.06, indicating access to the central nervous system. We have identified four Phase I metabolites after oral administration. The major metabolic routes are N-demethylation, aliphatic hydroxylation and O-methylation of a demethylenate intermediate. Discussion. Pharmacokinetic and pharmacodynamic analysis of methylone showed a correlation between plasma concentrations and enhancement of the locomotor activity. A contribution of metabolites in the activity of methylone after oral administration is suggested. Present results will be helpful to understand the time course of the effects of this drug of abuse in humans.
Note: Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.pnpbp.2013.04.007
It is part of: Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2013, vol. 45, p. 64-72
Related resource: http://dx.doi.org/10.1016/j.pnpbp.2013.04.007
URI: http://hdl.handle.net/2445/47623
ISSN: 0278-5846
Appears in Collections:Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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