Department of Psychiatry, Narcology and Medical Psychology, Poltava State Medical University, Poltava, Ukraine.
Department of Nervous Diseases with Neurosurgery and Medical Genetics, Poltava State Medical University, Poltava, Ukraine.
Neurochem Res. 2022 Oct;47(10):2909-2924. doi: 10.1007/s11064-022-03646-5. Epub 2022 Jun 11.
A complex pathogenesis involving several physiological systems is theorized to underline the development of depressive disorders. Depression is accompanied by circadian regulation disruption and interaction with the functioning of both central and peripheral oscillators. Many aspects of melatonin function unite these systems. The use of drugs for circadian rhythm disorders could inspire a potential treatment strategy for depression. Melatonin plays an essential role in the regulation of circadian rhythms. It exerts effect by activating two types of melatonin receptors, type 1A (MT1) and 1B (MT2). These are G-protein-coupled receptors, predominantly located in the central nervous system. MT1/MT2 agonists could be a useful treatment approach according to all three prevalent theories of the pathogenesis of depression involving either monoamines, synaptic remodeling, or immune/inflammatory events. MT1/MT2 receptors can be a potential target for novel antidepressants with impact on concentrations of neurotrophins or neurotransmitters, and reducing levels of pro-inflammatory cytokines. There is an interesting cross-talk mediated via the physical association of melatonin and serotonin receptors into functional heteromers. The antidepressive and neurogenetic effects of MT1/MT2 agonists can also be caused by the inhibition of the acid sphingomyelinase, leading to reduced ceramide, or increasing monoamine oxidase A levels in the hippocampus. Compounds targeting MT1 and MT2 receptors could have potential for new anti-depressants that may improve the quality of therapeutic interventions in treating depression and relieving symptoms. In particular, a combined effect on MT1 and/or MT2 receptors and neurotransmitter systems may be useful, since the normalization of the circadian rhythm through the melatonergic system will probably contribute to improved treatment. In this review, we discuss melatonergic receptors as a potential additional target for novel drugs for depression.
一种涉及多个生理系统的复杂发病机制被认为是导致抑郁障碍发展的原因。抑郁症伴随着昼夜节律调节紊乱，并与中枢和外周振荡器的功能相互作用。许多褪黑素功能的方面将这些系统联系在一起。用于昼夜节律障碍的药物的使用可能为抑郁症的潜在治疗策略提供灵感。褪黑素在昼夜节律的调节中起着重要作用。它通过激活两种类型的褪黑素受体，即 1A 型（MT1）和 1B 型（MT2）来发挥作用。这些受体是 G 蛋白偶联受体，主要位于中枢神经系统。根据涉及单胺、突触重塑或免疫/炎症事件的三种流行的抑郁症发病机制理论，MT1/MT2 激动剂可能是一种有用的治疗方法。MT1/MT2 受体可能是新型抗抑郁药的潜在靶点，这些药物可以影响神经营养因子或神经递质的浓度，并降低促炎细胞因子的水平。褪黑素和 5-羟色胺受体通过物理关联形成功能性异源二聚体，介导了有趣的串扰。MT1/MT2 激动剂的抗抑郁和神经发生作用也可能是由于酸性鞘磷脂酶的抑制，导致神经酰胺减少，或增加海马中单胺氧化酶 A 的水平。靶向 MT1 和 MT2 受体的化合物可能具有成为新型抗抑郁药的潜力，这可能会改善治疗抑郁症和缓解症状的治疗干预质量。特别是，对 MT1 和/或 MT2 受体和神经递质系统的联合作用可能是有用的，因为通过褪黑素系统使昼夜节律正常化可能有助于改善治疗效果。在这篇综述中，我们讨论了褪黑素受体作为新型抗抑郁药物的潜在附加靶点。
