The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders: A Potential Novel Treatment?
The Role of Muscarinic Receptors in the Pathophysiology of Mood Disorders: A Potential Novel Treatment?
复制标题
DOI：
10.2174/1570159x13666150612230045
复制
发表时间：
2015
影响因子：
5.3
通讯作者：
Gibbons A
中科院分区：
文献类型：
--
作者：
Jeon WJ;Dean B;Scarr E;Gibbons A
中枢胆碱能系统与心境障碍的病理生理学有关。中枢胆碱能神经递质活性的不平衡被认为是这些疾病典型的躁狂和抑郁发作的原因。胆碱能激动剂和拮抗剂对情绪状态影响的神经药理学研究为这一假设提供了相当大的支持。此外，最近的临床研究表明，泛CHRM拮抗剂东莨菪碱在患有重性抑郁症（MDD）或双相情感障碍（BPD）（如双相抑郁症）的个体中产生速效抗抑郁作用，与传统情绪稳定剂和抗抑郁药的延迟治疗反应形成对比。本文综述了最近的数据，从神经影像学，死后和遗传学研究支持参与毒蕈碱胆碱能受体（CHRM），特别是CHRM 2，在MDD和BPD的病理生理。因此，选择性靶向CHRM且对周围神经系统影响可忽略不计的新型药物可能会在BPD和MDD患者中产生更快速和更稳健的临床改善。
The central cholinergic system has been implicated in the pathophysiology of mood disorders. An imbalance in central cholinergic neurotransmitter activity has been proposed to contribute to the manic and depressive episodes typical of these disorders. Neuropharmacological studies into the effects of cholinergic agonists and antagonists on mood state have provided considerable support for this hypothesis. Furthermore, recent clinical studies have shown that the pan-CHRM antagonist, scopolamine, produces rapid-acting antidepressant effects in individuals with either major depressive disorder (MDD) or bipolar disorder (BPD), such as bipolar depression, contrasting the delayed therapeutic response of conventional mood stabilisers and antidepressants. This review presents recent data from neuroimaging, post-mortem and genetic studies supporting the involvement of muscarinic cholinergic receptors (CHRMs), particularly CHRM2, in the pathophysiology of MDD and BPD. Thus, novel drugs that selectively target CHRMs with negligible effects in the peripheral nervous system might produce more rapid and robust clinical improvement in patients with BPD and MDD.