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

The Journal of Pharmacology and Experimental Therapeutics
Yoshihiro KitagawaMutsuyoshi Matsushita

Abstract

Transient receptor potential vanilloid 1 (TRPV1) activation in peripheral sensory nerve is known to be associated with various pain-related diseases, thus TRPV1 has been the focus as a target for drug discovery. In this study, we characterized the pharmacological profiles 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 TRPV1 antagonist. JTS-653 displaced [(3)H]resiniferatoxin binding to human and rat TRPV1. JTS-653 competitively antagonized the capsaicin-induced activation of human TRPV1 with pA(2) values of 10.1. JTS-653 also inhibited proton-induced activation of human and rat TRPV1 with IC(50) values of 0.320 and 0.347 nM, respectively. Electrophysiological studies indicated that JTS-653 blocked heat-induced inward currents in rat TRPV1 with IC(50) values of 1.4 nM. JTS-653 showed weak or no inhibitory effects on other TRP channels, receptors, and enzymes. JTS-653 significantly prevented capsaicin-induced mechanical hyperalgesia at 1 mg/kg p.o. and attenuated carrageenan-induced mechanical hyperalgesia at 0.3 mg/kg p.o. JTS-653 significantly attenuated carrageenan-induced thermal hyperalgesia at 0.1 mg/kg p.o. an...Continue Reading

References

Feb 29, 2000·British Journal of Pharmacology·D SmartJ B Davis
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·S W HwangU Oh
May 24, 2001·Proceedings of the National Academy of Sciences of the United States of America·M TominagaM Masu
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·Susan M HuangVincenzo Di Marzo
Feb 6, 2003·The Journal of Biological Chemistry·Constance J ChuJ Michael Walker
Sep 13, 2003·British Journal of Pharmacology·Feng XuToshihiko Iijima
Sep 28, 2004·American Journal of Respiratory and Critical Care Medicine·David A GronebergK Fan Chung
Mar 30, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Narender R GavvaJean-Claude Louis
Jul 27, 2007·The Journal of Pharmacology and Experimental Therapeutics·Narender R GavvaJames J S Treanor
Jan 1, 2009·Nature Reviews. Drug Discovery·Ardem PatapoutianClifford J Woolf
Jan 29, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andras GaramiAndrej A Romanovsky
Nov 26, 2010·The Journal of Pharmacology and Experimental Therapeutics·Tomonari WatabikiNobuya Matsuoka
Feb 3, 2011·The EMBO Journal·Eduardo AneirosChristian Grimm
Jun 22, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jing YaoFeng Qin
Aug 2, 2011·Nature Reviews. Drug Discovery·Magdalene M MoranArpad Szallasi

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Citations

Jun 8, 2013·Journal of Natural Products·Sergio M BorghiWaldiceu A Verri
Sep 25, 2012·The Journal of Urology·Yoshihiro KitagawaMutsuyoshi Matsushita
Dec 16, 2016·Medicinal Research Reviews·Mojgan Aghazadeh TabriziPier Andrea Borea
Dec 7, 2013·British Journal of Pharmacology·Shijin YinHongzhen Hu
Sep 7, 2020·Annals of the New York Academy of Sciences·Satyanarayana Achanta, Sven-Eric Jordt
Sep 26, 2020·Annual Review of Pharmacology and Toxicology·Dorien BampsThomas Voets

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