Hashimoto K, Maeda H, Hirai K, Goromaru T
Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University, Hiroshima, Japan.
Eur J Pharmacol. 1993 Apr 1;228(5-6):247-56. doi: 10.1016/0926-6917(93)90057-w.
The present study was undertaken to examine the drug interactions between 3,4-methylenedioxymethamphetamine (MDMA) and paroxetine or several compounds including the 3,4-methylenedioxybenzyl (piperonyl) group in mice. The time course of radioactivity in the mouse brain after i.v. administration of the tracer amount (approximately 70 ng/kg) of [3H]MDMA was altered significantly by coinjection of carrier MDMA (15 mg/kg) or by pretreatment with paroxetine (10 mg/kg, i.p., 5 min). Furthermore, the radioactivity in the brain 60 min after injection of [3H]MDMA was increased significantly by pretreatment with paroxetine, but not by pretreatment with 6-nitroquipazine, fluoxetine, clomipramine, GBR 12909 or desipramine, indicating that paroxetine-induced alteration of the brain radioactivity was not due to the inhibitory effect of 5-hydroxytryptamine (5-HT) uptake of paroxetine. The radioactivity in the brain 60 min after injection of [3H]MDMA was increased significantly by pretreatment with 3,4-methylenedioxyamphetamine (MDA), MDMA, 1-piperonylpiperazine and N, alpha-dimethylpiperonylamine, but not by pretreatment with piperonylacetone, piperonyl butoxide and piperonyl isobutyrate. HPLC analyses indicated that the alteration of brain radioactivity 60 min after injection of [3H]MDMA was, in part, due to inhibition in the metabolism of [3H]MDMA to radioactive metabolite(s). The present results suggest that a specific mechanism for the 3,4-methylenedioxyphenyl group which rapidly alters the disposition and metabolism of [3H]MDMA may exist in brain and peripheral organs of mice.
本研究旨在检测3,4-亚甲基二氧甲基苯丙胺（摇头丸）与帕罗西汀或几种含3,4-亚甲基二氧苄基（胡椒基）的化合物在小鼠体内的药物相互作用。静脉注射微量（约70 ng/kg）[3H]摇头丸后，小鼠脑内放射性的时间进程因同时注射载体摇头丸（15 mg/kg）或帕罗西汀预处理（10 mg/kg，腹腔注射，5分钟）而显著改变。此外，帕罗西汀预处理可使注射[3H]摇头丸后60分钟时脑内放射性显著增加，但6-硝基喹哌嗪、氟西汀、氯米帕明、GBR 12909或去甲丙咪嗪预处理则无此作用，这表明帕罗西汀引起的脑内放射性改变并非由于其对5-羟色胺（5-HT）摄取的抑制作用。3,4-亚甲基二氧苯丙胺（MDA）、摇头丸、1-胡椒基哌嗪和N,α-二甲基胡椒基胺预处理可使注射[3H]摇头丸后60分钟时脑内放射性显著增加，但胡椒基丙酮、胡椒基丁醚和异丁酸胡椒酯预处理则无此作用。高效液相色谱分析表明，注射[3H]摇头丸后60分钟时脑内放射性的改变部分是由于[3H]摇头丸代谢为放射性代谢产物的过程受到抑制。目前的结果表明，小鼠脑和外周器官中可能存在一种特定机制，该机制可迅速改变[3H]摇头丸的分布和代谢，其与3,4-亚甲基二氧苯基有关。
