Maier Julian, Niello Marco, Rudin Deborah, Daws Lynette C, Sitte Harald H
Center for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
Department of Cellular and Integrative Physiology, University of Texas Health, San Antonio, TX, USA.
Handb Exp Pharmacol. 2021;266:199-214. doi: 10.1007/164_2021_469.
Organic cation transporters 1-3 (OCT1-3, SLC22A1-3) and the plasma membrane monoamine transporter (PMAT, SLC29A4) play a major role in maintaining monoaminergic equilibrium in the central nervous system. With many psychoactive substances interacting with OCT1-3 and PMAT, a growing literature focuses on characterizing their properties via in vitro and in vivo studies. In vitro studies mainly aim at characterizing compounds as inhibitors or substrates of murine, rat, and human isoforms. The preponderance of studies has put emphasis on phenylalkylamine derivatives, but ketamine and opioids have also been investigated. Studies employing in vivo (knockout) models mostly concentrate on the interaction of psychoactive substances and OCT3, with an emphasis on stress and addiction, pharmacokinetics, and sensitization to psychoactive drugs. The results highlight the importance of OCT3 in the mechanism of action of psychoactive compounds. Concerning in vivo studies, a veritable research gap concerning OCT1, 2, and PMAT exists. This review provides an overview and summary of research conducted in this field of research.
有机阳离子转运体1 - 3（OCT1 - 3，SLC22A1 - 3）和质膜单胺转运体（PMAT，SLC29A4）在维持中枢神经系统单胺能平衡中起主要作用。由于许多精神活性物质与OCT1 - 3和PMAT相互作用，越来越多的文献聚焦于通过体外和体内研究来表征它们的特性。体外研究主要旨在将化合物表征为小鼠、大鼠和人类异构体的抑制剂或底物。研究大多着重于苯烷基胺衍生物，但氯胺酮和阿片类药物也已被研究。采用体内（基因敲除）模型的研究大多集中在精神活性物质与OCT3的相互作用上，重点关注应激和成瘾、药代动力学以及对精神活性药物的致敏作用。结果突出了OCT3在精神活性化合物作用机制中的重要性。关于体内研究，存在一个关于OCT1、2和PMAT的实际研究空白。本综述提供了该研究领域已开展研究的概述和总结。
