Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan.
Eur J Pharmacol. 2011 Jun 25;660(2-3):318-25. doi: 10.1016/j.ejphar.2011.03.050. Epub 2011 Apr 9.
3,4-methylenedioxymethamphetamine (MDMA) is a psychoactive stimulant abused by young people as the recreational drug ecstasy. Other compounds, either deliberately added or present as byproducts, are often found in MDMA tablets and can unexpectedly interact with each other. The aim of this study was to evaluate the pharmacodynamic effects of interactions caused by concomitants in MDMA tablets on extracellular dopamine and serotonin (5-HT) by microdialysis in the striatum of ethylcarbamate-anesthetized rats. Baseline levels of dopamine and 5-HT in the striatum were 16.5±7.7 and 3.5±1.7 nM (mean±standard deviation), respectively. After a single administration of MDMA (10 mg/kg, i.p.), a dramatic increase in extracellular dopamine (Cmax: 36.1-fold vs. baseline) and 5-HT levels (Cmax: 9.3-fold vs. baseline) was observed. When rats were co-administered with methamphetamine (1, 5 or 10 mg/kg) with MDMA, the dopamine levels induced by MDMA increased in a methamphetamine-dose-dependent manner (Cmax: 2.5-, 3.5-, and 3.8-fold vs. MDMA). A similar trend was observed in 5-HT levels (Cmax: 1.1-, 1.3-, and 1.8-fold vs. MDMA). In contrast, ketamine and caffeine showed synergistic effects on the monoamine levels induced by MDMA, whereas the individual administration of either of these compounds did not affect monoamine levels. Ketamine (1, 5 mg/kg) decreased the dopamine levels induced by MDMA (Cmax: 0.9- and 0.7-fold vs. MDMA) and increased the 5-HT levels induced by MDMA (Cmax: 1.4- and 1.6-fold vs. MDMA), and co-administration of caffeine (20 mg/kg) with MDMA increased dopamine levels (Cmax: 1.7-fold vs. MDMA). These results suggest that exposure to multiple drugs in addition to MDMA can have neurotoxic effects.
3,4-亚甲二氧基甲基苯丙胺（MDMA）是一种致幻性兴奋剂，被年轻人用作娱乐性毒品摇头丸滥用。其他化合物，无论是故意添加的还是作为副产物存在的，通常都存在于 MDMA 片剂中，并可能意外地相互作用。本研究的目的是通过微透析评估乙基卡巴酸盐麻醉大鼠纹状体中 MDMA 片剂中伴随物相互作用引起的多巴胺和 5-羟色胺（5-HT）的药效学效应。纹状体中多巴胺和 5-HT 的基线水平分别为 16.5±7.7 和 3.5±1.7 nM（平均值±标准偏差）。单次给予 MDMA（10 mg/kg，ip）后，细胞外多巴胺（Cmax：与基线相比增加 36.1 倍）和 5-HT 水平（Cmax：与基线相比增加 9.3 倍）显著增加。当大鼠与 MDMA 一起给予甲基苯丙胺（1、5 或 10 mg/kg）时，MDMA 诱导的多巴胺水平呈甲基苯丙胺剂量依赖性增加（Cmax：2.5-、3.5-和 3.8 倍与 MDMA 相比）。在 5-HT 水平中观察到类似的趋势（Cmax：1.1-、1.3-和 1.8 倍与 MDMA 相比）。相比之下，氯胺酮和咖啡因对 MDMA 诱导的单胺水平具有协同作用，而这些化合物中的任何一种单独给药均不会影响单胺水平。氯胺酮（1、5 mg/kg）降低了 MDMA 诱导的多巴胺水平（Cmax：0.9-和 0.7 倍与 MDMA 相比），并增加了 MDMA 诱导的 5-HT 水平（Cmax：1.4-和 1.6 倍与 MDMA 相比），而咖啡因（20 mg/kg）与 MDMA 联合使用可增加多巴胺水平（Cmax：1.7 倍与 MDMA 相比）。这些结果表明，除 MDMA 之外，接触多种药物可能具有神经毒性作用。
