TRPM8 拮抗剂

TRPM8 antagonist 2 (Compound 14) is a potent and selective TRPM8 antagonist, with an IC ₅₀ of 0.2 nM, used in the research of neuropathic pain syndromes. TRPM8 antagonist 2 potently inhibits menthol-induced increase in intracellular Ca ²⁺ levels in Ca ²⁺ fluorimetric assays in HEK293 cells stably expressing the rat isoform of TRPM8 channels (IC ₅₀ , 40 nM).

TRPM8 antagonist 2 (1, 10, and 30 mg/kg, s.c.) shows a marked, dose-dependent antinociceptive activity, and inhibits wet-dog shakes (WDS)-like cold hypersensitivity in mice by 63% at 30 mg/kg. In addition, TRPM8 antagonist 2 (0.1 and 1 μg, s.c.) attenuates Oxaliplatin (OXP)-induced cold allodynia in mice.