Schmidt C J, Taylor V L
Merrell Dow Research Institute, Cincinnati, OH 45215.
Eur J Pharmacol. 1988 Oct 26;156(1):121-31. doi: 10.1016/0014-2999(88)90154-9.
Acute peripheral administration of either the (+) or (-) stereoisomer of methylenedioxymethamphetamine (MDMA) to rats results in a rapid loss of tryptophan hydroxylase (TPH) activity in several brain regions. This decline in enzyme activity precedes a decrease in serotonin (5-HT) concentrations in the same areas. An initial rise in the concentration of 5-hydroxyindole acetic acid after drug administration suggests that an increase in the turnover of 5-HT is an early event in the development of these changes. Unsuccessful attempts to reproduce the in vivo effects of MDMA on TPH activity using in vitro preparations such as cortical slices or the mouse mastocytoma cell line, P-815, suggested a requirement for an intact neuronal system or metabolism of the drug. Injection of MDMA directly into several brain regions also had no effect on TPH activity or 5-HT concentrations. However, when brain concentrations of MDMA were maintained using a constant i.c.v. infusion, TPH activity declined as observed following peripheral administration. The results, therefore, indicate that the acute effect of MDMA on 5-HT synthesis is a direct central effect of the drug which may be triggered by a sustained increase in transmitter turnover.
给大鼠外周急性注射亚甲基二氧甲基苯丙胺（MDMA）的（+）或（-）立体异构体，会导致几个脑区的色氨酸羟化酶（TPH）活性迅速丧失。这种酶活性的下降先于同一区域血清素（5-HT）浓度的降低。给药后5-羟吲哚乙酸浓度最初升高，表明5-HT周转增加是这些变化发生过程中的早期事件。使用诸如皮质切片或小鼠肥大细胞瘤细胞系P-815等体外制剂来重现MDMA对TPH活性的体内效应的尝试未成功，这表明需要完整的神经元系统或药物代谢。将MDMA直接注射到几个脑区也对TPH活性或5-HT浓度没有影响。然而，当通过持续的脑室内输注维持脑内MDMA浓度时，TPH活性如外周给药后观察到的那样下降。因此，结果表明MDMA对5-HT合成的急性效应是药物的直接中枢效应，这可能由递质周转的持续增加引发。
