Department of Pharmacology and Therapeutic Chemistry (Pharmacology Section), University of Barcelona, 08028 Barcelona, Spain.
Eur Neuropsychopharmacol. 2012 Mar;22(3):231-6. doi: 10.1016/j.euroneuro.2011.07.009. Epub 2011 Aug 6.
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.
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.
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.
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.
我们描述了一种研究甲卡西酮（4-甲基甲卡西酮）在大鼠体内药理学作用靶点的方法，旨在阐明该滥用药物的作用机制。
我们在大鼠皮质或纹状体的分离突触体或组织膜制剂中进行了体外实验，研究了甲卡西酮对单胺摄取的影响，以及该药物对几种特定放射性配体的置换作用。
在大鼠皮质或纹状体的分离突触体中，甲卡西酮对 5-羟色胺（5-HT）的摄取抑制作用的 IC ₅₀值低于对多巴胺（DA）摄取的抑制作用（IC ₅₀值分别为 0.31±0.08 和 0.97±0.05μM）。此外，甲卡西酮以浓度依赖的方式竞争性置换 [³H]帕罗西汀和 [³H]WIN35428 的结合（Ki 值分别为 17.55±0.78μM 和 1.53±0.47μM），表明其对 DA 膜转运体的亲和力大于 5-HT。通过研究大鼠膜中 [³H]氯氮平和 [³H]雷氯必利的结合，评估了甲卡西酮对 5-HT₂和 D₂受体的亲和力谱。甲卡西酮对 5-HT₂受体的亲和力大于对 D₂受体的亲和力。
这些结果表明，甲卡西酮与 5-HT 和 DA 转运体和受体相互作用，必须表现出与安非他命类化合物等其他精神活性药物相似的模式。
