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 IC50 value lower than that of dopamine (DA) uptake (IC50=0.31 +/- 0.08 and 0.97 +/- 0.05 mu M, respectively). Moreover, mephedrone displaced competitively both [H-3] paroxetine and [H-3]WIN35428 binding in a concentration-dependent manner (Ki values of 17.55 +/- 0.78 mu M and 1.53 +/- 0.47 mu M, respectively), indicating a greater affinity for DA than for 5-HT membrane transporters. The affinity profile of mephedrone for the 5-HT2 and D-2 receptors was assessed by studying [H-3]ketanserin and [H-3] raclopride binding in rat membranes. Mephedrone showed a greater affinity for the 5-HT2 than for the D-2 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. (C) 2011 Elsevier B.V. and ECNP. All rights reserved.