National Institute of Pharmaceutical Education and Research (NIPER), Department of Pharmaceutics, Mohali, Punjab, India.
Expert Opin Ther Pat. 2011 Nov;21(11):1673-91. doi: 10.1517/13543776.2011.623127.
The potential therapeutic applications of thyrotropin-releasing hormone (TRH) have attracted attention, based on its broad-spectrum neuropharmacological action rather than its endocrine properties. These central nervous system (CNS)-mediated effects provide the rationale for use of TRH and its analogs in the treatment of brain and spinal injury, and CNS disorders like schizophrenia, Alzheimer's disease, epilepsy, amyotrophic lateral sclerosis, Parkinson's disease, depression, shock and ischemia.
This review summarizes the patent literature and advances in the discovery and development of novel TRH analogs over the past 20 years. It provides a comprehensive overview of the development of new TRH analogs, giving emphasis to their pharmaceutical profile.
The use of TRH in the treatment of various CNS disorders has been proven clinically. However, TRH itself is a poor drug candidate due to its short plasma half-life (5 min), poor biopharmaceutical properties (low intestinal and CNS permeability) and endocrine side effect. Nevertheless, researchers have come up with metabolically stable, more potent and selective TRH analogs and prodrugs. Taltirelin, one of the TRH analogs, has been approved under the trade name of Ceredist(®) in Japan for the treatment of spinocerebellar degeneration. Several other TRH analogs are in various stages of preclinical or clinical development.
促甲状腺激素释放激素 (TRH) 具有广泛的神经药理学作用，而不是其内分泌特性，因此其潜在的治疗应用引起了关注。这些中枢神经系统 (CNS) 介导的作用为 TRH 及其类似物在脑和脊髓损伤以及精神分裂症、阿尔茨海默病、癫痫、肌萎缩侧索硬化症、帕金森病、抑郁症、休克和缺血等 CNS 疾病的治疗中的应用提供了依据。
本文综述了过去 20 年来在发现和开发新型 TRH 类似物方面的专利文献和进展。它全面概述了新型 TRH 类似物的开发，重点介绍了它们的药物特性。
TRH 已被证明可用于治疗各种 CNS 疾病。然而，由于其血浆半衰期（5 分钟）短、生物制药特性（低肠和 CNS 通透性）差以及内分泌副作用，TRH 本身是一种较差的药物候选物。尽管如此，研究人员还是提出了代谢稳定、更有效和选择性更高的 TRH 类似物和前药。TRH 类似物之一的塔尔替林（taltirelin）已在日本以 Ceredist（®）的商品名获得批准，用于治疗脊髓小脑变性。其他几种 TRH 类似物处于临床前或临床开发的不同阶段。
