J Pharmacol Exp Ther 2020 05 26;373(2):239-247. Epub 2020 Feb 26.
Discovery Research R&D, Kissei Pharmaceutical Co., Ltd., Azumino, Japan (O.N., Y.F., T.H., A.M., JI.K., H.H., Y.M., F.T.) and Department of Continence Medicine, the University of Tokyo Graduate School of Medicine, Tokyo, Japan (N.A., Y.I.).
Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (A-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized KPR-5714 (-[()-3,3-difluoro-4-hydroxy-1-(2-1,2,3-triazol-2-yl)butan-2-yl]-3-fluoro-2-[5-(4-fluorophenyl)-1-pyrazol-3-yl]benzamide), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels. Read More