Fleckenstein A E, Haughey H M, Metzger R R, Kokoshka J M, Riddle E L, Hanson J E, Gibb J W, Hanson G R
Department of Pharmacology and Toxicology, University of Utah, 30 South 2000 East RM 201, Salt Lake City, UT, USA.
Eur J Pharmacol. 1999 Oct 1;382(1):45-9. doi: 10.1016/s0014-2999(99)00588-9.
High-dose administrations of amphetamine, methamphetamine, cathinone, methcathinone or methylenedioxymethamphetamine rapidly decrease dopamine and serotonin transporter function in vivo, as assessed in striatal synaptosomes obtained from drug-treated rats. In contrast, high-dose injections of fenfluramine, cocaine or methylphenidate had little or no effect on the activity of these transporters. Interestingly, the capacity of these agents to directly alter dopamine and serotonin uptake, as assessed in vitro by direct application to rat striatal synaptosomes, did not predict their potential to modulate transporter activity following in vivo administration. These findings demonstrate heretofore-unreported differences in the effects of these agents on monoamine transporter function, and a distinction between drug effects after direct application in vitro vs. administration in vivo.
通过对药物处理大鼠纹状体突触体的评估发现，高剂量施用苯丙胺、甲基苯丙胺、卡西酮、甲卡西酮或亚甲基二氧甲基苯丙胺会迅速降低体内多巴胺和血清素转运体的功能。相比之下，高剂量注射芬氟拉明、可卡因或哌甲酯对这些转运体的活性几乎没有影响。有趣的是，通过直接应用于大鼠纹状体突触体在体外评估这些药物直接改变多巴胺和血清素摄取的能力，并不能预测它们在体内给药后调节转运体活性的潜力。这些发现证明了这些药物对单胺转运体功能的影响存在迄今未报道的差异，以及体外直接应用与体内给药后药物效应之间的区别。
