RGM8-51 is a β-lactam derivative, potent, selective TRPM8 antagonist with IC50 of 1.06 and 1.74 uM for rat and human TRPM8, respectively.
RGM8-51 does not have any ability to activate TRPM8 channels, but produces a concentration-dependent inhibition of menthol activation.
RGM8-51 is selective for cold-activated TRPM8 channels, displays no agonist or antagonist profile in cool-activated TRPA1 channels and has negligible activity as TRPV3 and ASIC3 channel antagonists.
RGM8-51 (1 µM) inhibited menthol-activated currents in rTRPM8-expressing HEK293 cells.
RGM8-51 exhibits in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy.
RGM8-51 reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve.
RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia.