Biological Activity
KPR-2579 does not distress temperature of the body at any given dose. It helps to block the activation of C-fiber single-unit afferent activities (SAAs)stimulated by acetic acid (AA).''KPR-2579 is a potent and selective transient receptor potential melastatin 8 (TRPM8; CRM1) antagonist (IC50 = 80/89 nM against EC80 MeOH-induced Ca2+ response in human/r at CRM1 HEK293T transfectants) with good selectivity (IC50 >30 μM against ligand-induced Ca2+ influx using hTRPA1hTRPV1or hTRPV4 transfectants) and oral availability (59% post 10 mg/kg p.o.; rats). KPR-2579 exhibits in vivo efficacy against icilin-induced wet-dog shakes (WDS; by 31/73/100% with 1/3/10 mg/kg p.o. 1h prior to icilin i.p.; female rats) and distension-induced rhythmic bladder contraction (by 70/89% with 0.1/0.3 mg/kg i.v.; male rats) without negative cardiovascular effects.
