Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination
Pharmacokinetic and pharmacodynamic effects of methylphenidate and MDMA administered alone or in combination
复制标题
DOI：
10.1017/s1461145713001132
复制
发表时间：
2014-03-01
影响因子：
4.8
通讯作者：
Liechti, Matthias E.
中科院分区：
文献类型：
--
作者：
Hysek, Cedric M.;Simmler, Linda D.;Liechti, Matthias E.
哌醋甲酯和3，4-亚甲基二氧基甲基苯丙胺(MDMA，“摇头丸”)是广泛滥用的精神活性药物。哌醋甲酯通过阻断突触前再摄取转运蛋白来增加脑多巴胺和去甲肾上腺素水平。MDMA通过相同的转运体释放5-羟色胺、多巴胺和去甲肾上腺素。哌醋甲酯和MDMA之间可能存在药效学相互作用。这项研究采用双盲、安慰剂对照、交叉设计，比较了在健康受试者中单独或联合应用哌醋甲酯和MDMA的药效学和药代动力学效应。尽管哌醋甲酯本身具有精神刺激作用，但它并不能增强MDMA的精神刺激作用。与单独应用MDMA或MDMA相比，联合应用MDMA和MDMA的血流动力学和不良反应显著增加。哌醋甲酯不改变MDMA的药代动力学，反之亦然。哌甲酸甲酯和MDMA有一些主观的苯丙胺型效应；然而，125 mg的MDMA比60 mg的哌甲酸甲酯更能增加积极情绪，而且哌甲酸甲酯对活性和浓度的促进作用比MDMA更强。哌醋甲酯和MDMA对面部情绪识别的影响不同。哌醋甲酯增强了对悲伤和恐惧面孔的识别，而MDMA则降低了对负面情绪的识别。此外，本研究还发现了对MDMA的急性药效耐受，但没有发现哌醋甲酯。总而言之，与单独使用两种药物相比，联合使用哌醋甲酯和MDMA并不会产生更多的精神活性作用，但可能会增强心血管和不良反应。这一发现可能对评估联合精神刺激剂滥用的风险具有临床意义。试用登记识别码：NCT01465685(http://clinicaltrials.gov/ct2/show/NCT01465685).
Methylphenidate and 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') are widely misused psychoactive drugs. Methylphenidate increases brain dopamine and norepinephrine levels by blocking the presynaptic reuptake transporters. MDMA releases serotonin, dopamine and norepinephrine through the same transporters. Pharmacodynamic interactions of methylphenidate and MDMA are likely. This study compared the pharmacodynamic and pharmacokinetic effects of methylphenidate and MDMA administered alone or in combination in healthy subjects using a double-blind, placebo-controlled, crossover design. Methylphenidate did not enhance the psychotropic effects of MDMA, although it produced psychostimulant effects on its own. The haemodynamic and adverse effects of co-administration of methylphenidate and MDMA were significantly higher compared with MDMA or methylphenidate alone. Methylphenidate did not change the pharmacokinetics of MDMA and vice versa. Methylphenidate and MDMA shared some subjective amphetamine-type effects; however, 125mg of MDMA increased positive mood more than 60mg of methylphenidate, and methylphenidate enhanced activity and concentration more than MDMA. Methylphenidate and MDMA differentially altered facial emotion recognition. Methylphenidate enhanced the recognition of sad and fearful faces, whereas MDMA reduced the recognition of negative emotions. Additionally, the present study found acute pharmacodynamic tolerance to MDMA but not methylphenidate. In conclusion, the combined use of methylphenidate and MDMA does not produce more psychoactive effects compared with either drug alone, but potentially enhances cardiovascular and adverse effects. The findings may be of clinical importance for assessing the risks of combined psychostimulant misuse. Trial registration identification number: NCT01465685 (http://clinicaltrials.gov/ct2/show/NCT01465685).