Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-4255, USA.
Curr Top Med Chem. 2011;11(17):2151-8. doi: 10.2174/156802611796904825.
TRPV1 has emerged as a promising therapeutic target for pain as well as a broad range of other conditions such as asthma or urge incontinence. The identification of resiniferatoxin as an ultrapotent ligand partially able to dissect the acute activation of TRPV1 from subsequent desensitization and the subsequent intense efforts in medicinal chemistry have revealed that TRPV1 affords a dramatic landscape of opportunities for pharmacological manipulation. While agonism and antagonism have represented the primary directions for drug development, the pharmacological complexity of TRPV1 affords additional opportunities. Partial agonism/partial antagonism, its modulation by signaling pathways, variable desensitization, and slow kinetics of action can all be exploited through drug design.
TRPV1 已成为疼痛以及哮喘或急迫性尿失禁等多种疾病的有前途的治疗靶点。作为一种超高效配体，树脂毒素的发现部分能够将 TRPV1 的急性激活与随后的脱敏区分开来，随后在药物化学方面的大量努力揭示了 TRPV1 为药理学操作提供了广阔的机会。虽然激动剂和拮抗剂一直是药物开发的主要方向，但 TRPV1 的药理学复杂性提供了更多的机会。部分激动/部分拮抗、信号通路的调节、可变脱敏和缓慢的作用动力学都可以通过药物设计来利用。
