Hiramatsu M, DiStefano E, Chang A S, Cho A K
Department of Pharmacology, UCLA School of Medicine 90024-1735.
Eur J Pharmacol. 1991 Nov 5;204(2):135-40. doi: 10.1016/0014-2999(91)90697-o.
Interpretation of the in vivo actions of 3,4-methylenedioxymethamphetamine (MDMA) is complicated by the formation of the active metabolite, 3,4-methylenedioxyamphetamine (MDA). This study evaluates the role of MDA in the dopamine releasing actions of (+)-MDMA. In the study, rats were given subcutaneous doses of (+)-MDMA and concentrations of monoamines and their metabolites in striatal dialysate were measured at 15 min intervals. In parallel experiments, plasma concentrations of (+)- and (-)-MDMA and MDA were determined by GC/MS procedures. The time course of MDMA levels was comparable for the two isomers as were their bioavailabilities. In contrast, the plasma levels of MDA were about three times higher after (+)-MDMA. (+)-MDMA caused a rapid increase in striatal dialysate levels of dopamine and decreased extracellular levels of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). There was a significant correlation between dopamine concentration in striatal dialysate and plasma MDMA concentration, but not with plasma MDA. These results indicate that MDMA itself has stereoselective actions on dopamine neurons. However, the higher plasma MDA levels after (+)-MDMA may account for part of the enantiomeric differences in the behavioral and neurotoxicological effects of MDMA.
3,4-亚甲基二氧甲基苯丙胺（MDMA）体内作用的解读因活性代谢物3,4-亚甲基二氧苯丙胺（MDA）的形成而变得复杂。本研究评估了MDA在（+）-MDMA多巴胺释放作用中的作用。在该研究中，给大鼠皮下注射（+）-MDMA，并每隔15分钟测量纹状体透析液中单胺及其代谢物的浓度。在平行实验中，通过气相色谱/质谱法测定（+）-和（-）-MDMA以及MDA的血浆浓度。两种异构体的MDMA水平随时间变化的过程及其生物利用度相当。相比之下，（+）-MDMA给药后MDA的血浆水平约高出三倍。（+）-MDMA导致纹状体透析液中多巴胺水平迅速升高，二羟基苯乙酸（DOPAC）和高香草酸（HVA）的细胞外水平降低。纹状体透析液中的多巴胺浓度与血浆MDMA浓度之间存在显著相关性，但与血浆MDA浓度无关。这些结果表明，MDMA本身对多巴胺神经元具有立体选择性作用。然而，（+）-MDMA给药后较高的血浆MDA水平可能是MDMA行为和神经毒理学效应中对映体差异的部分原因。
