TRPA1 agonist-3

TRPA1 agonist-3 is a selective and orally active TRPA1 agonist, with EC 50 values of 50.05 μM and 314.04 μM for human and mouse TRPA1, respectively. TRPA1 agonist-3 does not activate hTRPV1, mTRPV2, hTRPV3, hTRPV4, hTRPC6, or hTRPM8 channels. TRPA1 agonist-3 alleviates inflammatory pain in mice through a channel desensitization mechanism ^[1].

In Vivo, TRPA1 agonist-3 (compound NMTA) (10-40 mg/kg, p.o., once) alleviates CFA (Complete Freund’s Adjuvant) (plantar injection p.i., 20 μL)-induced inflammatory pain in male C57BL/6J mice^[1]. TRPA1 agonist-3 (10-40 mg/kg, p.o. once) has selective desensitization of TRPA1 rather than direct inhibition of heat-sensitive channels in male C57BL/6J mice^[1]. TRPA1 (10-40 mg/kg, p.o., once) agonist-3 has antinociceptive effect on cold-induced pain in male C57BL/6J mice^[1].

In Vitro, TRPA1 agonist-3 (compound NMTA) (50 μM, 24 h) activates hTRPA1 channels in a concentration dependent manner, leading to Ca2+ inffux in HEK-293T cells^[1]. TRPA1 agonist-3 exerts analgesic effects mediated through TRPA1 desensitization^[1].

References:
[1]. Sun C, et al. Identification of a Nonelectrophilic and Selective TRPA1 Agonist for Alleviation of Inflammatory Pain through Channel Desensitization. ACS Chem Neurosci. 2025 Sep 3;16(17):3257-3266.