Ononetin

Ononetin, a natural deoxybenzoin, is a potent and selective TRPM3 channel blocker with an IC₅₀ of 0.3 μM^[1]. In Vitro: Ononetin (1-10 μM) completely and reversibly abrogates Ca²⁺ entry and ionic currents through recombinantly expressed TRPM3α2 and block the pregnenolone sulphate-inducible Ca²⁺ entry in primary cultures of mouse or rat dorsal root ganglia (DRG) neurones, indicating biological activity towards endogenously expressed TRPM3^[1].
Oxidative intermediates of Ononetin may be involved in activating TRPA1, but not in the block of TRPM3 by Ononetin^[1]. In Vivo: Ononetin (10 mg/kg, i.p.) treatment completely reverses established Freund's Complete Adjuvant (FCA)-induced heat hypersensitivity, demonstrating that the loss of hypersensitivity in Trpm3^-/- mice is unlikely to be caused by developmental or compensatory mechanisms and suggests that TRPM3 may be a tractable target for inflammatory pain^[2].