Tsai Shih-Jen
Department of Psychiatry, Taipei Veterans General Hospital, Taiwan.
Med Hypotheses. 2006;67(5):1185-8. doi: 10.1016/j.mehy.2006.05.005. Epub 2006 Jun 22.
Major depressive disorder (MDD) is a common mental disease, but with an unknown etiology. Antidepressants are the main biological treatment for MDD. However, current antidepressive agents have a slow onset of effect and a substantial proportion of MDD patients do not clinically improve, despite maximal medication. Thus, the exploration for new antidepressants with novel strategies may help to develop faster and more effective antidepressant agents. Studies in the recent decades have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels and activating the BDNF-signaling pathway may play an important role in their therapeutic mechanism. Cysteamine is a natural product of cells and constitutes the terminal region of the CoA molecule. Recent work has found that cysteamine and a related agent, cystamine, have neuroprotective effects in Huntington's disease (HD) mice, through enhancing central BDNF levels. Furthermore, cystamine or cysteamine injection could increase serum BDNF levels in wild-type mice as well as HD mice. Since activation of the BDNF-dependent pathway plays an important role in the mechanism of antidepressant therapeutic action, cystamine or its derivatives could have potential antidepressant therapeutic effects. Among these agents, pantethine may be one of the most promising agents. It is a naturally occurring compound which can be administered orally with negligible side effects, and is metabolized to cysteamine. Further evaluation of the therapeutic and toxic effects of these cysteamine-related antidepressant agents in MDD animal models is needed before any clinical application.
重度抑郁症（MDD）是一种常见的精神疾病，但其病因不明。抗抑郁药是治疗MDD的主要生物疗法。然而，目前的抗抑郁药起效缓慢，尽管进行了最大剂量的药物治疗，仍有相当一部分MDD患者在临床上没有改善。因此，探索采用新策略的新型抗抑郁药可能有助于开发更快、更有效的抗抑郁药。近几十年来的研究表明，抗抑郁药可提高中枢脑源性神经营养因子（BDNF）水平，激活BDNF信号通路可能在其治疗机制中起重要作用。半胱胺是细胞的天然产物，构成辅酶A分子的末端区域。最近的研究发现，半胱胺和一种相关药物胱胺，通过提高中枢BDNF水平，对亨廷顿舞蹈病（HD）小鼠具有神经保护作用。此外，注射胱胺或半胱胺可提高野生型小鼠以及HD小鼠的血清BDNF水平。由于BDNF依赖途径的激活在抗抑郁治疗作用机制中起重要作用，胱胺或其衍生物可能具有潜在的抗抑郁治疗效果。在这些药物中，泛硫乙胺可能是最有前景的药物之一。它是一种天然存在的化合物，口服给药副作用可忽略不计，且可代谢为半胱胺。在任何临床应用之前，需要进一步评估这些与半胱胺相关的抗抑郁药在MDD动物模型中的治疗和毒性作用。
