期刊
BRITISH JOURNAL OF PHARMACOLOGY
卷 167, 期 2, 页码 407-420出版社
WILEY
DOI: 10.1111/j.1476-5381.2012.01998.x
关键词
butylone; mephedrone; methylone; dopamine; serotonin; locomotor activity
资金
- Generalitat de Catalunya [SGR977]
- Plan Nacional sobre Drogas [2010/005]
- Ministerio de Ciencia e Innovacion [SAF2010-15948]
- Generalitat de Catalunya and Martinez-Clemente
- Plan Nacional sobre Drogas
BACKGROUND AND PURPOSE Here, we have compared the neurochemical profile of three new cathinones, butylone, mephedrone and methylone, in terms of their potential to inhibit plasmalemmal and vesicular monoamine transporters. Their interaction with 5-HT and dopamine receptors and their psychostimulant effect was also studied. EXPERIMENTAL APPROACH Locomotor activity was recorded in mice following different doses of cathinones. Monoamine uptake assays were performed in purified rat synaptosomes. Radioligand-binding assays were carried out to assess the affinity of these compounds for monoamine transporters or receptors. KEY RESULTS Butylone, mephedrone and methylone (525 mg.kg-1) caused hyperlocomotion, which was prevented with ketanserin or haloperidol. Methylone was the most potent compound inhibiting both [3H]5-HT and [3H]dopamine uptake with IC50 values that correlate with its affinity for dopamine and 5-HT transporter. Mephedrone was found to be the cathinone derivative with highest affinity for vesicular monoamine transporter-2 causing the inhibition of dopamine uptake. The affinity of cathinones for 5-HT2A receptors was similar to that of MDMA. CONCLUSIONS AND IMPLICATIONS Butylone and methylone induced hyperlocomotion through activating 5-HT2A receptors and increasing extra-cellular dopamine. They inhibited 5-HT and dopamine uptake by competing with substrate. Methylone was the most potent 5-HT and dopamine uptake inhibitor and its effect partly persisted after withdrawal. Mephedrone-induced hyperlocomotion was dependent on endogenous 5-HT. Vesicular content played a key role in the effect of mephedrone, especially for 5-HT uptake inhibition. The potency of mephedrone in inhibiting noradrenaline uptake suggests a sympathetic effect of this cathinone.
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