Gould Todd D, Chen Guang, Manji Husseini K
Laboratory of Molecular Pathophysiology, Building 49, Room B1EE16, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Clin Neurosci Res. 2002 Dec;2(3-4):193-212. doi: 10.1016/S1566-2772(02)00044-0. Epub 2002 Nov 14.
Mood stabilizers represent a class of drugs that are efficacious in the treatment of bipolar disorder. The most established medications in this class are lithium, valproic acid, and carbamazepine. In addition to their therapeutic effects for treatment of acute manic episodes, these medications often are useful as prophylaxis against future episodes and as adjunctive antidepressant medications. While important extracellular effects have not been excluded, most available evidence suggests that the therapeutically relevant targets of this class of medications are in the interior of cells. Herein we give a prospective of a rapidly evolving field, discussing common effects of mood stabilizers as well as effects that are unique to individual medications. Mood stabilizers have been shown to modulate the activity of enzymes, ion channels, arachidonic acid turnover, G protein coupled receptors and intracellular pathways involved in synaptic plasticity and neuroprotection. Understanding the therapeutic targets of mood stabilizers will undoubtedly lead to a better understanding of the pathophysiology of bipolar disorder and to the development of improved therapeutics for the treatment of this disease. Furthermore, the involvement of mood stabilizers in pathways operative in neuroprotection suggests that they may have utility in the treatment of classical neurodegenerative disorders.
心境稳定剂是一类对双相情感障碍治疗有效的药物。该类药物中最常用的是锂盐、丙戊酸和卡马西平。除了对急性躁狂发作有治疗作用外,这些药物还常用于预防未来发作以及作为辅助抗抑郁药物。虽然尚未排除重要的细胞外作用,但大多数现有证据表明,这类药物的治疗相关靶点在细胞内部。在此,我们对一个快速发展的领域进行展望,讨论心境稳定剂的共同作用以及个别药物独有的作用。心境稳定剂已被证明可调节酶、离子通道、花生四烯酸代谢、G蛋白偶联受体以及参与突触可塑性和神经保护的细胞内信号通路的活性。了解心境稳定剂的治疗靶点无疑将有助于更好地理解双相情感障碍的病理生理学,并推动开发更有效的该疾病治疗方法。此外,心境稳定剂参与神经保护相关信号通路表明它们可能对经典神经退行性疾病的治疗有用。