Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6

Detalles Bibliográficos
Autores: Martínez-Clemente, José, López Arnau, Raúl, Carbó Banús, Marcel·lí, Pubill Sánchez, David, Camarasa García, Jordi, Escubedo Rafa, Elena
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/53992
Acceso en línea:https://hdl.handle.net/2445/53992
Access Level:acceso abierto
Palabra clave:Amfetamines
Sistema nerviós central
Cervell
Farmacocinètica
Efectes fisiològics
Drogues de disseny
Amphetamines
Central nervous system
Brain
Pharmacokinetics
Physiological effect
Designer drugs
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spelling Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamicsMartínez-Clemente, JoséLópez Arnau, RaúlCarbó Banús, Marcel·líPubill Sánchez, DavidCamarasa García, JordiEscubedo Rafa, ElenaAmfetaminesSistema nerviós centralCervellFarmacocinèticaEfectes fisiològicsDrogues de dissenyAmphetaminesCentral nervous systemBrainPharmacokineticsPhysiological effectDesigner drugsFe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity.Springer Verlag2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/53992Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: http://dx.doi.org/10.1007/s00213-013-3108-7Psychopharmacology, 2013, vol. 229, num. 2, p. 295-306http://dx.doi.org/10.1007/s00213-013-3108-7http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6(c) Springer Verlag, 2013info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/539922026-05-27T06:46:51Z
dc.title.none.fl_str_mv Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
title Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
spellingShingle Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
Martínez-Clemente, José
Amfetamines
Sistema nerviós central
Cervell
Farmacocinètica
Efectes fisiològics
Drogues de disseny
Amphetamines
Central nervous system
Brain
Pharmacokinetics
Physiological effect
Designer drugs
title_short Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
title_full Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
title_fullStr Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
title_full_unstemmed Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
title_sort Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics
dc.creator.none.fl_str_mv Martínez-Clemente, José
López Arnau, Raúl
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Camarasa García, Jordi
Escubedo Rafa, Elena
author Martínez-Clemente, José
author_facet Martínez-Clemente, José
López Arnau, Raúl
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Camarasa García, Jordi
Escubedo Rafa, Elena
author_role author
author2 López Arnau, Raúl
Carbó Banús, Marcel·lí
Pubill Sánchez, David
Camarasa García, Jordi
Escubedo Rafa, Elena
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Amfetamines
Sistema nerviós central
Cervell
Farmacocinètica
Efectes fisiològics
Drogues de disseny
Amphetamines
Central nervous system
Brain
Pharmacokinetics
Physiological effect
Designer drugs
topic Amfetamines
Sistema nerviós central
Cervell
Farmacocinètica
Efectes fisiològics
Drogues de disseny
Amphetamines
Central nervous system
Brain
Pharmacokinetics
Physiological effect
Designer drugs
description Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6
publishDate 2013
dc.date.none.fl_str_mv 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/2445/53992
url https://hdl.handle.net/2445/53992
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/10.1007/s00213-013-3108-7
Psychopharmacology, 2013, vol. 229, num. 2, p. 295-306
http://dx.doi.org/10.1007/s00213-013-3108-7
http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6
dc.rights.none.fl_str_mv (c) Springer Verlag, 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer Verlag, 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301629

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