Department of Internal Medicine I, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120 Halle (Saale), Germany.
Expert Opin Investig Drugs. 2009 Nov;18(11):1765-72. doi: 10.1517/13543780903329089.
Neurodegenerative disorders such as Alzheimer's disease or amyotrophic lateral sclerosis as well as peripheral neuropathies are difficult to treat due to a limited range of effective drugs. Neurotrophic growth factors promote neuronal survival and differentiation and could hence be interesting tools to treat these diseases. Their therapeutic use is limited due their short half-life, their inability to cross the BBB and potential side effects including tumor promotion. SR 57746A is a non-peptide, orally active compound that exhibits neuroprotective effects in various model systems in vitro and in vivo. SR 57746A shows--amongst other activities--agonistic activity on 5-HT(1A) receptors. Several clinical trials examined SR 57746A in patients with Alzheimer's disease, amyotrophic lateral sclerosis or chemotherapy-induced peripheral sensory neuropathy. This article reviews the preclinical and clinical data on SR 57746A and points out potential future applications of this compound. However, due to disapointing results in phase III trials, Sanofi-Aventis recently decided to discontinue the development of this drug.
神经退行性疾病，如阿尔茨海默病或肌萎缩性侧索硬化症以及周围神经病，由于有效的药物有限，因此难以治疗。神经营养生长因子促进神经元存活和分化，因此可以作为治疗这些疾病的有趣工具。由于其半衰期短、不能穿过血脑屏障以及包括促进肿瘤在内的潜在副作用，它们的治疗用途受到限制。SR 57746A 是一种非肽、口服活性化合物，在体外和体内的各种模型系统中均表现出神经保护作用。SR 57746A 除其他活性外，还对 5-HT（1A）受体具有激动作用。几项临床试验在阿尔茨海默病、肌萎缩性侧索硬化症或化疗诱导的周围感觉神经病患者中检查了 SR 57746A。本文综述了 SR 57746A 的临床前和临床数据，并指出了该化合物的潜在未来应用。然而，由于 III 期临床试验的结果令人失望，赛诺菲-安万特最近决定停止该药物的开发。
