TRPM8 antagonist 14

TRPM8 Antagonist is a potent and selective TRPM8 antagonist, with an IC50 of 0.2 nM, used in the research of neuropathic pain syndromes.

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

Research Areas >> Neurological Disease

IC50: 0.2 nM (TRPM8)[1]

TRPM8 Antagonist (Compound 14) is a potent and selective TRPM8 antagonist, with an IC50 of 0.2 nM, used in the research of neuropathic pain syndromes. TRPM8 Antagonist potently inhibits menthol-induced increase in intracellular Ca2+ levels in Ca2+ fluorimetric assays in HEK293 cells stably expressing the rat isoform of TRPM8 channels (IC50, 40 nM)[1].

TRPM8 Antagonist (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 (0.1 and 1 μg, s.c.) attenuates Oxaliplatin (OXP)-induced cold allodynia in mice[1].

Mice[1] Icilin, a TRPM8 agonist, is dissolved in 20% DMSO and 1% Tween 80 in distilled water and injected intraperitoneally (i.p.) in a volume of 10 mL/kg. Each animal is acclimatized for 30 min for two consecutive days before icilin administration. TRPM8 Antagonist (compound 14) stock is prepared in DMSO and diluted in saline for injections. Gabapentin is dissolved in saline and administered s.c. at the dose of 25 mg/kg 60 min prior to icillin injection. Control animals receive the vehicle injection[1].

[1]. Bertamino A, et al. Identification of a Potent Tryptophan-Based TRPM8 Antagonist With in Vivo Analgesic Activity. J Med Chem. 2018 Jul 10. doi: 10.1021/acs.jmedchem.8b00545.

capsaicin | Capsazepine | EIPA | Diphenyleneiodonium chloride | HC-030031 | SKF-96365 | HC 067047 | AMG 9810 | GSK-1016790A | SAR7334 | PF-4840154 | RN-1734 | AMG-517 | SB-366791 | IcilinAG-3-5