Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland.
Department of Pharmacology, School of Medicine in Katowice, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland.
Neuropeptides. 2019 Jun;75:1-17. doi: 10.1016/j.npep.2019.02.002. Epub 2019 Feb 15.
Selective serotonin reuptake inhibitors (SSRIs) are drugs of first choice in the therapy of moderate to severe depression and anxiety disorders. Their primary mechanism of action is via influence of the serotonergic (5-HT) system, but a growing amount of data provides evidence for other non-monoaminergic players in SSRI effects. It is assumed that neuropeptides, which play a role as neuromodulators in the CNS, are involved in their mechanism of action. In this review we focus on six neuropeptides: corticotropin-releasing factor - CRF, galanin - GAL, oxytocin - OT, vasopressin - AVP, neuropeptide Y - NPY, and orexins - OXs. First, information about their roles in depression and anxiety disorders are presented. Then, findings describing their interactions with the 5-HT system are summarized. These data provide background for analysis of the results of published preclinical and clinical studies related to SSRI effects on the neuropeptide systems. We also report findings showing how modulation of neuropeptide transmission influences behavioral and neurochemical effects of SSRIs. Finally, future research necessary for enriching our knowledge of SSRI mechanisms of action is proposed. Recognition of new molecular targets for antidepressants will have a significant effect on the development of novel therapeutic strategies for mood-related disorders.
选择性 5-羟色胺再摄取抑制剂（SSRIs）是治疗中重度抑郁症和焦虑症的首选药物。它们的主要作用机制是通过影响 5-羟色胺能（5-HT）系统，但越来越多的数据为 SSRI 作用的其他非单胺能机制提供了证据。据推测，作为中枢神经系统神经调质发挥作用的神经肽可能参与其作用机制。在这篇综述中，我们重点介绍了六种神经肽：促肾上腺皮质激素释放因子（CRF）、甘丙肽（GAL）、催产素（OT）、加压素（AVP）、神经肽 Y（NPY）和食欲素（OXs）。首先，介绍了它们在抑郁症和焦虑症中的作用信息。然后，总结了描述它们与 5-HT 系统相互作用的发现。这些数据为分析与 SSRI 对神经肽系统的作用相关的已发表的临床前和临床研究结果提供了背景。我们还报告了发现，表明神经肽传递的调节如何影响 SSRI 的行为和神经化学作用。最后，提出了丰富我们对 SSRI 作用机制的认识所需的未来研究。识别新型抗抑郁药的新分子靶标将对情绪相关障碍的新型治疗策略的发展产生重大影响。
