Li Xian-Tao
School of Medicine, Jingchu University of Technology, Jingmen, China.
Research group of Neurological and Metabolic Disease, School of Medicine, Jingchu University of Technology, Jingmen, China.
Transl Psychiatry. 2024 Oct 2;14(1):411. doi: 10.1038/s41398-024-03069-6.
Depression is a common and complex psychiatric illness with multiple clinical symptoms, even leading to the disability and suicide. Owing to the partial understanding of the pathogenesis of depressive-like disorders, available pharmacotherapeutic strategies are developed mainly based on the "monoamine hypothesis", resulting in a limited effectiveness and a number of adverse effects in the clinical practice. The concept of multiple pathogenic factors be helpful for clarifying the etiology of depression and developing the antidepressants. It is well documented that K channels serve crucial roles in modulating the neuronal excitability and neurotransmitter release in the brain, and abnormality of these channels participated in the pathogenic process of diverse central nervous system (CNS) pathologies, such as seizure and Alzheimer's disease (AD). The clinical and preclinical evidence also delineates that the involvement of several types of K channels in depressive-like behaviors appear to be evident, suggesting these channels being one of the multiple factors in the etiology of this debilitating disorder. Emerging data manifest that diverse antidepressants impact distinct K channels, such as Kv, Kir and K, meaning the functioning of these drug via a "multi-target" manner. On the other hand, the scenario of antidepressants impinging K channels could render an alternative interpretation for the pharmacological effectiveness and numerous side effects in clinical trials. Furthermore, these channels serve to be considered as a "druggable target" to develop novel therapeutic compound to antagonize this psychiatry.
抑郁症是一种常见且复杂的精神疾病，具有多种临床症状，甚至会导致残疾和自杀。由于对抑郁样障碍发病机制的部分理解，现有的药物治疗策略主要基于“单胺假说”制定，导致在临床实践中疗效有限且存在诸多不良反应。多种致病因素的概念有助于阐明抑郁症的病因并研发抗抑郁药。有充分的文献记载，钾通道在调节大脑神经元兴奋性和神经递质释放方面发挥着关键作用，这些通道的异常参与了多种中枢神经系统（CNS）疾病的发病过程，如癫痫和阿尔茨海默病（AD）。临床和临床前证据也表明，几种类型的钾通道参与抑郁样行为似乎很明显，这表明这些通道是这种使人衰弱的疾病病因中的多种因素之一。新出现的数据表明，多种抗抑郁药会影响不同的钾通道，如电压门控钾通道（Kv）、内向整流钾通道（Kir）和钙激活钾通道（KCa），这意味着这些药物通过“多靶点”方式发挥作用。另一方面，抗抑郁药作用于钾通道的情况可以为临床试验中的药理疗效和众多副作用提供另一种解释。此外，这些通道可被视为开发新型治疗化合物以对抗这种精神疾病的“可药用靶点”。
