Nash J F, Nichols D E
Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, OH 44106.
Eur J Pharmacol. 1991 Jul 23;200(1):53-8. doi: 10.1016/0014-2999(91)90664-c.
The acute effect of 3,4-methylenedioxyamphetamine (MDA) and three structural analogues on the extracellular concentrations of dopamine (DA) and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum was studied using in vivo microdialysis in awake, freely moving rats. MDA significantly (P less than 0.001) increased and decreased the extracellular concentrations of DA and its metabolites, respectively, following i.p. administration. Similarly, acute administration of the N-methyl (MDMA) and N-ethyl (MDE) derivatives of MDA significantly (P less than 0.05) increased the concentration of DA in the striatum. The alpha-ethyl homologue of MDMA, MBDB, increased the extracellular concentration of DA but significantly (P less than 0.05) less than MDA, MDMA, or MDE. The rank order of potency for these amphetamine derivatives to increase the extracellular concentration of DA was: MDA greater than MDMA greater than MDE greater than MBDB greater than vehicle. The increase in extracellular DA concentration following a single administration of these compounds was negatively correlated with the level of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the contralateral striatum measured 7 days following drug administration. Thus, extending the alkyl group on the nitrogen or alpha-carbon of MDA reduces the ability of these compounds both to increase acutely the extracellular concentration of DA and to produce long-lasting depletions of 5-HT in the brain.
利用体内微透析技术，在清醒、自由活动的大鼠中研究了3,4-亚甲基二氧基苯丙胺（MDA）及其三种结构类似物对纹状体中多巴胺（DA）及其主要代谢产物二羟基苯乙酸（DOPAC）和高香草酸（HVA）细胞外浓度的急性影响。腹腔注射MDA后，显著（P<0.001）增加和降低了DA及其代谢产物的细胞外浓度。同样，MDA的N-甲基（MDMA）和N-乙基（MDE）衍生物急性给药后，显著（P<0.05）增加了纹状体中DA的浓度。MDMA的α-乙基同系物MBDB增加了DA的细胞外浓度，但显著（P<0.05）低于MDA、MDMA或MDE。这些苯丙胺衍生物增加DA细胞外浓度的效力顺序为：MDA>MDMA>MDE>MBDB>溶剂。单次给予这些化合物后细胞外DA浓度的增加与给药7天后对侧纹状体中血清素（5-HT）及其主要代谢产物5-羟吲哚乙酸（5-HIAA）的水平呈负相关。因此，在MDA的氮或α-碳上延长烷基会降低这些化合物急性增加DA细胞外浓度以及在脑中产生5-HT长期耗竭的能力。
