Icilin is a synthetic cooling substance that acts as a potent TRPM8 channel activator with an EC₅₀ value of 0.2 ± 0.1μM¹. This compound also shown to activate TRPA1 ion channel but at higher concentrations. Activation of TRPM8 channel by icilin produces Na⁺ and Ca²⁺ ion influx that results in cellular depolarization and the feeling of cold. Icilin has the ability to produce behavioral activation in rats and mice^1-3.

TRPM8 is a Ca²⁺-permeable channel, a member of the ‘long' or melastatin (M) group of TRP channels and is activated by temperatures in the range of 8-28°C or by cooling compounds such as icilin. The TRPM8 gene is expressed and up-regulated in prostate cancer and other malignancies. TRPM8 channel is specifically expressed in temperature-sensing trigeminal and dorsal root ganglion neurons^1,4.