Benzodiazepines as Potent and Selective Bradykinin B1 Antagonists

Antagonism of the bradykinin B1 receptor was
demonstrated to be a potential treatment for chronic pain and
inflammation. Novel benzodiazepines were designed that
display subnanomolar affinity for the bradykinin B1 receptor
(Ki = 0.59 nM) and high selectivity against the bradykinin B2
receptor (Ki > 10 μM). In vivo efficacy, comparable to morphine, was demonstrated for lead compounds in a rodent
hyperalgesia model.

本研究揭示了阻断缓激肽B1受体可能成为治疗慢性疼痛和炎症的有效方法。研究人员设计了一系列新型苯二氮卓类药物，这些药物对缓激肽B1受体展现出亚纳摩尔亲和力（Ki = 0.59 nM），同时对缓激肽B2受体具有高度选择性（Ki > 10 μM）。在啮齿动物的超敏疼痛模型中，主要化合物的体内疗效与吗啡相当。