Hurd Y L, Ungerstedt U
Karolinska Institute, Department of Pharmacology, Stockholm, Sweden.
Eur J Pharmacol. 1989 Jul 18;166(2):251-60. doi: 10.1016/0014-2999(89)90066-6.
The in vivo neurochemical profile of recently synthesized dopamine (DA) uptake inhibitors (Lu 19-005, Lu 17-133 and GBR 12.921) is described. The antidepressant, nomifensine, as well as another typical DA uptake inhibitor, methylphenidate, was also tested with the microdialysis technique. Most of the new DA uptake inhibitors induced a gradual dose- and time-dependent accumulation of extracellular DA with a weak influence on DA metabolites, similar to that of methylphenidate. Nomifensine, however, caused a DA overflow during the first hour after injection. This was distinguishable from the effect of other uptake inhibitors but comparable to amphetamine. The moderate increase of DOPAC induced by nomifensine compared to the marked decrease produced by amphetamine corroborates reports that the DA 'release' induced by these drugs is mediated by different mechanisms, originating from different intracellular storage pools of DA. The fact that nomifensine can be distinguished from other uptake inhibitors shows clearly that evaluation of dynamic changes in transmitter overflow provides information pertinent to the overall neurochemical characterization of a drug.
本文描述了最近合成的多巴胺（DA）摄取抑制剂（Lu 19 - 005、Lu 17 - 133和GBR 12.921）的体内神经化学特征。抗抑郁药诺米芬辛以及另一种典型的DA摄取抑制剂哌甲酯也采用微透析技术进行了测试。大多数新的DA摄取抑制剂会引起细胞外DA逐渐呈剂量和时间依赖性积累，对DA代谢物影响较弱，这与哌甲酯类似。然而，诺米芬辛在注射后的第一个小时内会导致DA溢出。这与其他摄取抑制剂的作用不同，但与苯丙胺的作用相当。与苯丙胺引起的显著降低相比，诺米芬辛引起的3,4 - 二羟基苯乙酸（DOPAC）适度增加，这证实了关于这些药物诱导的DA“释放”由不同机制介导的报道，这些机制源于DA不同的细胞内储存池。诺米芬辛可与其他摄取抑制剂区分开来这一事实清楚地表明，对递质溢出动态变化的评估为药物的整体神经化学特征提供了相关信息。
