Icilin is a synthetic super-agonist of the transient receptor potential M8 (TRPM8) ion channel. Although structurally not related with menthol it produces an extreme sensation of cold both in humans and animals. It is almost 200 times more potent than menthol and 2.5 times more efficacious. Despite their similar effects icilin activates the TRPM8 receptor in a different way. Icilin is effective in an experimental model of itch. It is now used as a research tool for the study of TRP channels. Menthol, icilin, and cold all evoked stimulus-dependent [Ca2+]i responses in standard physiological solutions of pH 7.3. Increasing the extracellular [H+] from pH 7.3 to approximately pH 6 abolished responses to icilin and cold stimulation but did not affect responses to menthol. Icilin concentration-response curves were significantly shifted to the right when pH was lowered from 7.3 to 6.9, whereas those with menthol were unaltered in solutions of pH 6.1.
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