TRPM8 antagonist 14 is a tryptophan-derived selective TRPM8 antagonist with IC50 value of 0.2nM. It showed significant target coverage in both an icilin-induced WDS (at 1-30 mg/kg s.c.) and oxaliplatin-induced cold allodynia (at 0.1-1 μg s.c.) mice models.
TRPM8 antagonist 14 is an effective selective TRPM8 antagonist with IC50 of 0.2 nm, which is used in the study of neuropathic pain syndrome. TRPM8 antagonist can effectively inhibit the increase of intracellular Ca2 + level induced by menthol in HEK293 cells stably expressing TRPM8 channel rat isoforms (ic50,40nm). RPM8 antagonist (1,10 and 30 mg / kg, s.c.) showed significant antinociceptive activity in a dose-dependent manner and inhibited wet dog milkshake (WDS) - like cold hypersensitivity in mice by 63% at 30 mg / kg. In addition, TRPM8 antagonist (0.1 and 1 μ g, s.c.) objective to alleviate the cold pain induced by oxaliplatin (oxp) in mice[2]. In the wet dog shakes (WDS) assay, compound 14 (TRPM8 antagonist 14) dose-dependently blocks icilin-triggered shaking behaviors in mice. Upon local administration, compound 14 dose dependently inhibits cold allodynia evoked by the chemotherapy oxaliplatin in a murine model of peripheral neuropathy at microgram doses[3].
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