Laboratório de Imunofarmacologia, sala O4-202, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Avenida Antônio Carlos 6627, Pampulha, Belo Horizonte, CEP 31.270-901, Brazil,
CNS Drugs. 2014 Jan;28(1):45-61. doi: 10.1007/s40263-013-0128-0.
The number of approved new molecular entity drugs has been decreasing as the pharmaceutical company investment in research and development is increasing. As we face this painful crisis, called an innovation gap, there is increasing awareness that development of new uses of existing drugs may be a powerful tool to help overcome this obstacle because it takes too long, costs too much and can be risky to release drugs developed de novo. Consequently, drug repositioning is emerging in different therapeutic areas, including the pain research area. Worldwide, pain is the main reason for seeking healthcare, and pain relief represents an unmet global clinical need. Therefore, development of analgesics with better efficacy, safety and cost effectiveness is of paramount importance. Despite the remarkable advancement in research on cellular and molecular mechanisms underlying pain pathophysiology over the past three decades, target-based therapeutic opportunities have not been pursued to the same extent. Phenotypic screening remains a more powerful tool for drug development than target-based screening so far. It sounds somewhat heretical, but some multi-action drugs, rather than very selective ones, have been developed intentionally. In the present review, we first critically discuss the utility of drug repositioning for analgesic drug development and then show examples of 'old' drugs that have been successfully repositioned or that are under investigation for their analgesic actions. We conclude that drug repositioning should be more strongly encouraged to help build a bridge between basic research and pain relief worldwide.
随着制药公司在研发方面的投入不断增加，获得批准的新分子实体药物数量却在减少。当我们面临这种被称为创新差距的痛苦危机时，人们越来越意识到，开发现有药物的新用途可能是克服这一障碍的有力工具，因为从头开发新药既耗时又昂贵，而且风险很大。因此，药物重定位在不同的治疗领域都有出现，包括疼痛研究领域。在全球范围内，疼痛是寻求医疗保健的主要原因，而缓解疼痛则代表着未满足的全球临床需求。因此，开发具有更好疗效、安全性和成本效益的镇痛药至关重要。尽管在过去三十年中，细胞和分子机制在疼痛病理生理学方面的研究取得了显著进展，但基于靶点的治疗机会并没有得到同样程度的探索。表型筛选仍然是一种比基于靶点筛选更强大的药物开发工具。这听起来有些异端邪说，但一些多作用药物，而不是非常选择性的药物，已经被有意开发。在本综述中，我们首先批判性地讨论了药物重定位在镇痛药物开发中的应用，然后展示了一些“旧”药物成功重定位或正在研究其镇痛作用的例子。我们得出结论，应该更大力鼓励药物重定位，以帮助在基础研究和全球缓解疼痛之间架起桥梁。
