| Identification | Back Directory | [Name]
2H-1,4-Benzoxazine-8-carboxamide, 3,4-dihydro-3-(hydroxymethyl)-4-(5-methyl-2-pyridinyl)-N-[6-(2,2,2-trifluoroethoxy)-3-pyridinyl]-, (3S)- | [CAS]
942614-99-5 | [Synonyms]
JTS-653
2H-1,4-Benzoxazine-8-carboxamide, 3,4-dihydro-3-(hydroxymethyl)-4-(5-methyl-2-pyridinyl)-N-[6-(2,2,2-trifluoroethoxy)-3-pyridinyl]-, (3S)- | [Molecular Formula]
C23H21F3N4O4 | [MOL File]
942614-99-5.mol | [Molecular Weight]
474.43 |
| Hazard Information | Back Directory | [Uses]
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 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]. | 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.
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TRPV1 | [References]
[1] Yoshihiro Kitagawa, et al. Pharmacological characterization of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel transient receptor potential vanilloid 1 antagonist. J Pharmacol Exp Ther. 2012 Aug;342(2):520-8. DOI:10.1124/jpet.112.194027
[2] Yoshihiro Kitagawa, et al. Orally administered selective TRPV1 antagonist, JTS-653, attenuates chronic pain refractory to non-steroidal anti-inflammatory drugs in rats and mice including post-herpetic pain. J Pharmacol Sci. 2013;122(2):128-37. DOI:10.1254/jphs.12276fp |
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