AMG9678

AMG9678 is a potent, selective, orally active antagonist of TRPM8 with an IC50 of 31.2 nM[1].

Signaling Pathways >> Membrane Transporter/Ion Channel >> TRP Channel

Research Areas >> Others

TRPM8:31.2 nM (IC50)

TRPA1:0.6 μM (IC50)

AMG9678 potently inhibits the menthol and cold-induced increase in intracellular calcium in cells expressing rat TRPM8, the plasma half-life (T1/2) in rats is 7.6 h[1].

AMG9678 (0-100 mg/kg; p.o.; once) produces a significant and somewhat dose-dependent decrease in body temperature (Tb) in rats[1]. AMG9678 (30 mg/kg; p.o.; once daily for 4 consecutive days) decreases reduced body temperature after repeated dosing in rats[1]. Animal Model: Male Sprague Dawley rats weighing 200–350 g (6–12 weeks of age) [1] Dosage: 10, 30 and 100 mg/kg Administration: Oral administration, once or once daily for 4 consecutive days Result: Produced a significant and somewhat dose-dependent decrease in Tb at 10, 30 and 100 mg/kg. The magnitude of TRPM8 blockade-induced decrease in body temperature is reduced after repeated dosing. Effect of AMG9678 on Tb in rats. P value is for comparing compound administered rat Tb with vehicle administered rat Tb. End of the study plasma concentration is reported in μM. Asterisk indicates one-way ANOVA followed by Dunnett's MCT Compound Dose mg/kg (route) Max Tb decrease (°C) P value * Time post dosing (min) Plasma concentration AMG9678 10 (p.o.) 0.72 p < 0.001 60 0.04 ± 0.006 AMG9678 30 (p.o.) 0.70 p < 0.01 60 0.34 ± 0.1 AMG9678 100 (p.o.) 0.83 p < 0.05 60 0.36 ± 0.12

[1]. Gavva NR, et al. Transient receptor potential melastatin 8 (TRPM8) channels are involved in body temperature regulation. Mol Pain. 2012 May 9;8:36.