Laboratory of Physiology, Pharmacology and Psychopathology, Campus Chapecó, Federal University of South Frontier (UFFS), Chapecó, Santa Catarina, Brazil; Laboratory of Neurosciences, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciúma, SC, Brazil.
Laboratory of Physiology, Pharmacology and Psychopathology, Campus Chapecó, Federal University of South Frontier (UFFS), Chapecó, Santa Catarina, Brazil; State Secretary for Justice and Citizenship of Santa Catarina, Brazil.
Neurosci Biobehav Rev. 2018 Mar;86:36-50. doi: 10.1016/j.neubiorev.2017.12.012. Epub 2017 Dec 27.
Major depressive disorder (MDD) is a highly debilitating condition that is drawing considerable attention due to its high global prevalence and to the fact that treatments are still far from reaching the total number of patients affected. Among available treatment strategies, quetiapine is an important research target, due to antidepressant responses in patients resistant to classical treatments and in animals submitted to protocols that induce depressive-like behaviours. Quetiapine has a broad spectrum of action, within which are many mechanisms that seem to be related to the most effective antidepressant therapeutic responses. In this review, research results related to the pharmacokinetic profile, neurotransmitters, receptors and signalling molecular targets involved in the functional and structural plasticity of key brain regions in MDD are reported and discussed. Moreover, the physiological mechanisms, which are targets of quetiapine and are involved in both MDD and poor therapeutic response, are reported. The main adverse effects observed from therapeutic dosages and overdose are also described. Finally, the main mechanisms underlying the therapeutic response are highlighted.
重度抑郁症(MDD)是一种高度致残的疾病,由于其在全球的高患病率,以及治疗方法仍远未达到受影响患者的总数,因此引起了相当多的关注。在现有的治疗策略中,喹硫平是一个重要的研究目标,因为它对对抗传统治疗方法有反应的患者以及在诱导类似抑郁行为的动物模型中都有抗抑郁作用。喹硫平具有广泛的作用谱,其中有许多机制似乎与最有效的抗抑郁治疗反应有关。在这篇综述中,报告并讨论了与药代动力学特征、神经递质、受体和信号分子靶点相关的研究结果,这些靶点涉及 MDD 关键脑区的功能和结构可塑性。此外,还报告了喹硫平作用的生理机制,这些机制涉及 MDD 和治疗反应不佳,并描述了从治疗剂量和过量用药中观察到的主要不良反应。最后,强调了治疗反应的主要机制。