JTS-653

JTS-653 is a highly potent and selective transient receptor potential vanilloid 1 (TRPV1) antagonist in vitro and in vivo. JTS-653 attenuates chronic pain refractory to non-steroidal anti-inflammatory agents^[1]. In Vitro: JTS-653 inhibits proton-induced activation of human and rat TRPV1 with IC₅₀s of 0.320 and 0.347 nM, respectively^[1]. JTS-653 blocks heat-induced inward currents in rat TRPV1 with an IC₅₀ of 1.4 nM^[1].
In the competition experiments, JTS-653 displaces [³H]RTX binding to human and rat TRPV1 in a concentration-related manner with K_i values of 11.44 and 4.40 nM, respectively^[1].
JTS653 inhibits the 30 nM Capsaicin-induced activation of human and rat TRPV1 with IC₅₀s of 0.236 and 0.247 nM, respectively^[1]. In Vivo: JTS-653 significantly prevents Capsaicin-induced mechanical hyperalgesia at 1 mg/kg p.o. and attenuates Carrageenan-induced mechanical hyperalgesia at 0.3 mg/kg p.o. JTS-653 significantly attenuates Carrageenan-induced thermal hyperalgesia at 0.1 mg/kg p.o. and fully reverses at 0.3 mg/kg p.o. without affecting the volume of the Carrageenan-treated paw. JTS-653 shows a transient increase of body temperature at 0.3 mg/kg p.o.^[1].
JTS-653 attenuates chronic pain refractory to non-steroidal anti-inflammatory agents in rats and mice including post-herpetic pain. JTS-653 (0.3, 1, 3 mg/kg) shows its effect in a dose-related manner, with statistical significance at 0.3 mg/kg or above^[2].