JTS-653 is a potent and selective in vitro and in vivo antagonist of transient receptor potential vanilloid 1 (TRPV1). It effectively attenuates chronic pain resistant to non-steroidal anti-inflammatory drugs.

JTS-653 inhibits proton-induced activation of human and rat TRPV1 with IC 50 s of 0.320 and 0.347 nM, respectively[1].

JTS-653 blocks heat-induced inward currents in rat TRPV1 with an IC 50 of 1.4 nM[1]. In the competition experiments, JTS-653 displaces [ 3 H]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 IC 50 s of 0.236 and 0.247 nM, respectively[1].

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]. Animal Model: Male Sprague-Dawley rats aged 5 to 6 weeks[2]Dosage: 0.3, 1, 3 mg/kg Administration: 0.5 h, 2 h, 8 h, 25 h Result: Partially attenuated mechanical hyperalgesia in the L5 spinal nerve ligation model in rats at 0.3 mg/kg. Increased the paw withdrawal threshold (PWT) of the ipsilateral paw at 0.5, 2, and 8 h after the administration and its effect disappeared by 25 h after administration. Showed its maximum effect with 1 mg/kg at 2 h after administration.