DiNunzio James C, Williams Robert O
Division of Pharmaceutics, The University of Texas at Austin, Austin, TX 78712, USA.
Drug Dev Ind Pharm. 2008 Nov;34(11):1141-67. doi: 10.1080/03639040802020536.
The development of new pharmaceutical products has successfully addressed a multitude of disease states; however, new product development for treating disorders of the central nervous system (CNS) has lagged behind other therapeutic areas. This is due to several factors including the complexity of the diseases and the lack of technologies for delivery through the blood-brain barrier (BBB). This article examines the current state of six major CNS disease states: depression, epilepsy, multiple sclerosis (MS), neurodegenerative diseases (specifically Alzheimer's disease [AD]), neuropathic pain, and schizophrenia. Discussion topics include analysis of the biological mechanisms underlying each disease, currently approved products, and available animal models for development of new therapeutic agents. Analysis of currently approved therapies shows that all products depend on the molecular properties of the drug or prodrug to penetrate the BBB. Novel technologies, capable of enhancing BBB permeation, are also discussed relative to improving CNS therapies for these disease states.
新药品的研发已成功攻克了众多疾病状态;然而,用于治疗中枢神经系统(CNS)疾病的新产品研发却落后于其他治疗领域。这是由多种因素导致的,包括疾病的复杂性以及缺乏通过血脑屏障(BBB)进行递送的技术。本文探讨了六种主要中枢神经系统疾病状态的现状:抑郁症、癫痫、多发性硬化症(MS)、神经退行性疾病(特别是阿尔茨海默病[AD])、神经性疼痛和精神分裂症。讨论主题包括对每种疾病潜在生物学机制的分析、当前已获批的产品以及用于开发新治疗药物的可用动物模型。对当前已获批疗法的分析表明,所有产品都依赖于药物或前药的分子特性来穿透血脑屏障。还讨论了能够增强血脑屏障通透性的新技术,这些技术与改善针对这些疾病状态的中枢神经系统疗法相关。