Icilin is an agonist of nonselective cation channel TRPM8, with antiproliferative activity. TRPM8 is a cation channel activated by cold temperatures and the chemical stimuli menthol and icilin[3]. The synthetic supercooling drug, icilin, and its primary receptor target, the cation channel transient receptor potential (TRP) melastatin-8 (TRPM8), have been described as potent negative regulators of inflammation in the colon. In vitro, icilin potently inhibited the proliferation of murine and human CD4+ T cells, with the peripheral expansion of autoantigen-restricted T cells similarly diminished by the administration of icilin in mice[4]. Rats injected with icilin (0.5, 1, 2.5, 5mg/kg, i.p.) displayed dose-related WDS (wet-dog shakes) that were inhibited by pretreatment with a fixed dose of clonidine (0.15 mg/kg, s.c.). alpha(2)-adrenoceptor activation inhibits shaking induced by icilin and that increases in peripheral, as well as central, alpha(2)-adrenoceptor signaling oppose the behavioral stimulant effect of icilin[5].
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