Biological Activity
AMG517 is an orally active, highly potent and selective vanilloid receptor-1 (TRPV1; VR1; capsaicin receptor) antagonist th at blocks TRPV1-mediated cellular Ca2+ influx (h/r/m IC50/stimulant = 0.76 nM/1.01 nM/1.9 nM/500 nM capsaicin; 0.62 nM/0.5 nM/0.63 nM/acid (pH 5) using respective CHO transfectants; IC50 >20 μM against TRPV2/3/4, TRPA1, and TRPM8-mediated responses; <45% binding at 10 μM to 87 receptors, enzymes, and ion channels) and exhibits antihyperalgesic efficacy in vivo (capsaicin-induced flinch = ED50 = 0.33 mg/kg rats, p.o.; CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg rats, p.o.).
