AMG8379

AMG8379 is a potent, orally active and selective sulfonamide antagonist of the voltage-gated sodium channel NaV1.7, with IC₅₀s of 8.5 and 18.6 nM for hNaV1.7 and mNaV1.7, respectively. AMG8379 potently and reversibly blocks endogenous Tetrodotoxin (TTX)-sensitive sodium channels in dorsal root ganglia (DRG) neurons with an IC₅₀ of 3.1 nM^[1]. In Vitro: AMG8379 is 100 to 1000-fold selective over other NaV family members, including NaV1.4 expressed in muscle and NaV1.5 expressed in heart, as well as TTX-resistant NaV channels in DRG neurons^[1].
The IC₅₀ for AMG8379 inhibition of C-fiber spiking based on the level of firing in NaV1.7 KO mice representing complete pharmacological block of the NaV1.7-component of this assay is calculated. In this manner, the IC₅₀ for AMG8379 block is 47.0 ± 8.1 nM^[1]. In Vivo: AMG8379 (30-100 mg/kg; p.o.) inhibits Capsaicin-induced nociceptive behavior^[1].