{"title":"K+ 通道与抑郁症的关系以及抗抑郁药对这些通道的药理作用。","authors":"Xian-Tao Li","doi":"10.1038/s41398-024-03069-6","DOIUrl":null,"url":null,"abstract":"<p><p>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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> channels, such as Kv, Kir and K<sub>2P</sub>, meaning the functioning of these drug via a \"multi-target\" manner. On the other hand, the scenario of antidepressants impinging K<sup>+</sup> 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.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"14 1","pages":"411"},"PeriodicalIF":5.8000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447029/pdf/","citationCount":"0","resultStr":"{\"title\":\"The involvement of K<sup>+</sup> channels in depression and pharmacological effects of antidepressants on these channels.\",\"authors\":\"Xian-Tao Li\",\"doi\":\"10.1038/s41398-024-03069-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup> channels, such as Kv, Kir and K<sub>2P</sub>, meaning the functioning of these drug via a \\\"multi-target\\\" manner. On the other hand, the scenario of antidepressants impinging K<sup>+</sup> 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.</p>\",\"PeriodicalId\":23278,\"journal\":{\"name\":\"Translational Psychiatry\",\"volume\":\"14 1\",\"pages\":\"411\"},\"PeriodicalIF\":5.8000,\"publicationDate\":\"2024-10-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11447029/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Translational Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1038/s41398-024-03069-6\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-024-03069-6","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
The involvement of K+ channels in depression and pharmacological effects of antidepressants on these channels.
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 K2P, 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.
期刊介绍:
Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.