The preclinical pharmacology of mephedrone; not just MDMA by another name (2014)

ENGLISH:
The substituted beta-keto amphetamine mephedrone (4-methylmethcathinone) was banned in the UK in April 2010 but continues to be used recreationally in the UK and elsewhere. Users have compared its psychoactive effects to those of 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'). This review critically examines the preclinical data on mephedrone that has appeared over the last 2-3 years and, where relevant, compares the pharmacological effects of mephedrone in experimental animals with those obtained following MDMA administration. Both mephedrone and MDMA enhance locomotor activity and change rectal temperature in rodents. However both of these responses are of short duration following mephedrone compared to MDMA probably because mephedrone has a short plasma half-life and rapid metabolism. Mephedrone appears to have no pharmacologically active metabolites, unlike MDMA. There is also little evidence that mephedrone induces neurotoxic decrease in monoamine concentration in rat or mouse brain, again in contrast to MDMA. Mephedrone and MDMA both induce release of dopamine and 5-hydroxytryptamine (5-HT) in the brain as shown by in vivo and in vitro studies. The effect on 5-HT release in vivo is more marked with mephedrone even though both drugs have similar affinity for DAT and SERT in vitro. The profile of action of mephedrone on monoamine receptors and transporters suggests it could have a high abuse liability and several studies have found that mephedrone supports self-administration at a higher rate than MDMA. Overall, current data suggest that mephedrone not only differs from MDMA in its pharmacological profile, behavioural and neurotoxic effects but also differs from other cathinones.
FRANÇAIS :
Une étude parue dans le British Journal of Pharmacology attire l'attention sur la pharmacocinétique de la 4-méthylméthcathinone ou méphédrone, dérivé de la cathinone, psychostimulant actif qui bien que banni de Grande Bretagne en 2010 continue d'être consommé sur un mode récréatif en Grande Bretagne et partout ailleurs. Bien que les usagers considèrent les effets psychoactifs de la méphédrone comme similaires à ceux de la MDMA, leurs profils pharmacodynamiques et leurs effets diffèrent. A la différence de la MDMA, la méphédrone exerce une pénétration élevée dans le cerveau, avec un métabolisme et une clairance cérébrale rapides. Par ailleurs elle génère une libération plus importante de dopamine et agit tel un mixte de cocaïne-MDMA. De plus, leurs effets thermorégulateurs respectifs ne sont pas les mêmes : la méphédrone ne semble pas générer d'hyperthermie en dehors d'un usage combiné avec de la caféine. [Actualités des addictions 02/04/14]