TRPM8 Modulator

RN-1747 is a selective TRPV4 channel agonist, with EC₅₀ values of 0.77 μM, 4.0 μM and 4.1 μM for hTRPV4, mTRPV4 and rTRPV4, respectively. RN-1747 acts as an antagonist of TRPM8, with an IC₅₀ of 4 μM. Topical cutaneous administration of RN-1747 induces hypothermia, increases tail heat loss via cutaneous vasodilation, and promotes cold-seeking behavior in rats. Intracerebroventricular administration of RN-1747 does not induce hypothermia in rats.

Cannabitwinol is a selective thermosensitive TRP modulator and NF-κB inhibitor. Cannabitwinol inhibits TNFα-induced NF-κB-driven transcription and TNFα-induced IL-8 release, and exhibits anti-inflammatory and antioxidant activities. Cannabitwinol shows selectivity for cold-activated TRP channels, activating TRPA1 (EC₅₀ = 3.0 μM) and antagonizing TRPM8 (IC₅₀ = 3.9 μM), but has no significant affinity for heat-activated TRP channels such as TRPV1 and TRPV2. Cannabitwinol can be used in research related to inflammatory skin diseases, cold allodynia, and hyperalgesia.