Interaction of mephedrone with dopamine and serotonin targets in rats.


INTRODUCTION We described a first approach to the pharmacological targets of mephedrone (4-methyl-methcathinone) in rats to establish the basis of the mechanism of action of this drug of abuse. EXPERIMENTAL PROCEDURES We performed in vitro experiments in isolated synaptosomes or tissue membrane preparations from rat cortex or striatum, studying the effect of mephedrone on monoamine uptake and the displacement of several specific radioligands by this drug. RESULTS In isolated synaptosomes from rat cortex or striatum, mephedrone inhibited the uptake of serotonin (5-HT) with an IC ₅₀ value lower than that of dopamine (DA) uptake (IC ₅₀=0.31±0.08 and 0.97±0.0 5μM, respectively). Moreover, mephedrone displaced competitively both [³H]paroxetine and [³H]WIN35428 binding in a concentration-dependent manner (Ki values of 17.55±0.78μM and 1.53±0.47 μM, respectively), indicating a greater affinity for DA than for 5-HT membrane transporters. The affinity profile of mephedrone for the 5-HT₂ and D₂ receptors was assessed by studying [³H]ketanserin and [³H] raclopride binding in rat membranes. Mephedrone showed a greater affinity for the 5-HT₂ than for the D₂ receptors. DISCUSSION These results provide evidence that mephedrone, interacting with 5-HT and DA transporters and receptors must display a similar pattern of other psychoactive drugs such as amphetamine-like compounds.

DOI: 10.1016/j.euroneuro.2011.07.009

Extracted Key Phrases

4 Figures and Tables

Citations per Year

923 Citations

Semantic Scholar estimates that this publication has 923 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{MartnezClemente2012InteractionOM, title={Interaction of mephedrone with dopamine and serotonin targets in rats.}, author={Jos{\'e} Mart{\'i}nez-Clemente and E Escubedo and David Pubill and Jorge Camarasa}, journal={European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology}, year={2012}, volume={22 3}, pages={231-6} }