An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'

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 a...

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Autores: López Arnau, Raúl, Martínez-Clemente, José, Carbó Banús, Marcel·lí, Pubill Sánchez, David, Escubedo Rafa, Elena, Camarasa García, Jordi
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2013
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/47623
Acesso em linha:https://hdl.handle.net/2445/47623
Access Level:Acceso aberto
Palavra-chave:Amfetamines
Farmacocinètica
Rates (Animals de laboratori)
Locomoció animal
Amphetamines
Pharmacokinetics
Rats as laboratory animals
Animal locomotion
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repository_id_str
spelling An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'López Arnau, RaúlMartínez-Clemente, JoséCarbó Banús, Marcel·líPubill Sánchez, DavidEscubedo Rafa, ElenaCamarasa García, JordiAmfetaminesFarmacocinèticaRates (Animals de laboratori)Locomoció animalAmphetaminesPharmacokineticsRats as laboratory animalsAnimal locomotionMaterial 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.Elsevier B.V.2013201320132013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion9 p.application/pdfhttps://hdl.handle.net/2445/47623Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: http://dx.doi.org/10.1016/j.pnpbp.2013.04.007Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2013, vol. 45, p. 64-72http://dx.doi.org/10.1016/j.pnpbp.2013.04.007(c) Elsevier B.V., 2013info:eu-repo/semantics/openAccessoai:recercat.cat:2445/476232026-05-29T05:05:01Z
dc.title.none.fl_str_mv An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
title An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
spellingShingle An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
López Arnau, Raúl
Amfetamines
Farmacocinètica
Rates (Animals de laboratori)
Locomoció animal
Amphetamines
Pharmacokinetics
Rats as laboratory animals
Animal locomotion
title_short An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
title_full An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
title_fullStr An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
title_full_unstemmed An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
title_sort An integrated pharmacokinetic and pharmacodynamic study of a new drug of abuse, methylone, a synthetic cathinone sold as 'bath salts'
dc.creator.none.fl_str_mv López Arnau, Raúl
Martínez-Clemente, José
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Escubedo Rafa, Elena
Camarasa García, Jordi
author López Arnau, Raúl
author_facet López Arnau, Raúl
Martínez-Clemente, José
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Escubedo Rafa, Elena
Camarasa García, Jordi
author_role author
author2 Martínez-Clemente, José
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Escubedo Rafa, Elena
Camarasa García, Jordi
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Amfetamines
Farmacocinètica
Rates (Animals de laboratori)
Locomoció animal
Amphetamines
Pharmacokinetics
Rats as laboratory animals
Animal locomotion
topic Amfetamines
Farmacocinètica
Rates (Animals de laboratori)
Locomoció animal
Amphetamines
Pharmacokinetics
Rats as laboratory animals
Animal locomotion
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/47623
url https://hdl.handle.net/2445/47623
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.pnpbp.2013.04.007
Progress in Neuro-Psychopharmacology & Biological Psychiatry, 2013, vol. 45, p. 64-72
http://dx.doi.org/10.1016/j.pnpbp.2013.04.007
dc.rights.none.fl_str_mv (c) Elsevier B.V., 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Elsevier B.V., 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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