Kulkarni Shrinivas K, Dhir Ashish
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160 014, India.
Expert Rev Neurother. 2009 Jul;9(7):1021-34. doi: 10.1586/ern.09.40.
Major depression and anxiety are two of the major psychiatric disorders that have some overlapping pathophysiologies, the most significant being the dysfunction in the monoaminergic, GABAergic and glutamatergic systems. A large number of drugs that alter these neurotransmitter levels/systems are effective in the treatment of major depression and anxiety. However, full remission of the clinical symptoms has not been achieved, perhaps owing to the complex pathophysiology of the diseases. Thus, the search for newer targets and target-specific drugs continues. Recently, the role of sigma-receptors, particularly the sigma-1 receptor subtype, has been identified as a target for the pathophysiology of neuropsychiatric disorders, and sigma-1 receptor modulators are considered to be the drugs of the future for the treatment of major depression and anxiety. The present review attempts to discuss the role of sigma-1 receptors in the pathophysiology of major depression and anxiety and also tries to position the use of its receptor modulators in the treatment of these two major disorders. The role of sigma-1 receptors in the mechanism of antidepressant action of venlafaxine, bupropion, neurosteroids and one of the herbal antidepressants, berberine, is reviewed. Although, sigma-1 receptor modulators may be future therapeutic options, either as individual agents or adjuvants in the treatment of mental disorders, the topic needs further preclinical and clinical exploration.
重度抑郁症和焦虑症是两种主要的精神疾病，它们在病理生理学上存在一些重叠，其中最显著的是单胺能、γ-氨基丁酸能和谷氨酸能系统功能障碍。大量改变这些神经递质水平/系统的药物对重度抑郁症和焦虑症的治疗有效。然而，临床症状并未完全缓解，这可能是由于疾病复杂的病理生理学所致。因此，寻找新的靶点和针对特定靶点的药物的工作仍在继续。最近，σ受体，特别是σ-1受体亚型的作用已被确定为神经精神疾病病理生理学的一个靶点，σ-1受体调节剂被认为是未来治疗重度抑郁症和焦虑症的药物。本综述试图讨论σ-1受体在重度抑郁症和焦虑症病理生理学中的作用，并尝试阐述其受体调节剂在治疗这两种主要疾病中的应用。文中回顾了σ-1受体在文拉法辛、安非他酮、神经甾体以及一种草药抗抑郁药小檗碱的抗抑郁作用机制中的作用。尽管σ-1受体调节剂可能是未来治疗精神疾病的选择，无论是作为单一药物还是辅助药物，但这个话题仍需要进一步的临床前和临床探索。
