title: Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in the rat.
abstract: The TRPV1 capsaicin receptor is a non-selective cation channel localized in the cell membrane of a subset of primary sensory neurons and functions as an integrator molecule in nociceptive/inflammatory processes. The present paper characterizes the effects of SB366791, a novel TRPV1 antagonist, on capsaicin-evoked responses both in vitro and in vivo using rat models. SB366791 (100 and 500 nM) significantly inhibited capsaicin-evoked release of the pro-inflammatory sensory neuropeptide substance P from isolated tracheae, while it did not influence electrically induced neuropeptide release. It also decreased capsaicin-induced Ca2+ influx in cultured trigeminal ganglion cells in a concentration-dependent manner (0.5-10 microM) with an IC50 of 651.9 nM. In vivo 500 microg/kg i.p. dose of SB366791 significantly inhibited capsaicin-induced hypothermia, wiping movements and vasodilatation in the knee joint, while 2 mg/kg capsazepine was ineffective, its effect lasted for 1h. However, neither antagonist was able to inhibit capsaicin-evoked hypothermia in Balb/c mice. Based on these data SB366791 is a more selective and in vivo also a more potent TRPV1 receptor antagonist than capsazepine in the rat therefore, it may promote the assessment of the therapeutic utility of TRPV1 channel blockers.
authors.affiliation: Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Pécs, H-7643 Pécs, Szigeti u. 12, Hungary.
authors.forename: Angelika
authors.initials: A
authors.lastname: Varga
authors.forename: József
authors.initials: J
authors.lastname: Németh
authors.forename: Arpád
authors.initials: A
authors.lastname: Szabó
authors.forename: Jason J
authors.initials: JJ
authors.lastname: McDougall
authors.forename: Chunfen
authors.initials: C
authors.lastname: Zhang
authors.forename: Krisztián
authors.initials: K
authors.lastname: Elekes
authors.forename: Erika
authors.initials: E
authors.lastname: Pintér
authors.forename: János
authors.initials: J
authors.lastname: Szolcsányi
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Helyes
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007035:Hypothermia / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism; D010146:Pain / Q000378:metabolism* / Q000503:physiopathology; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D050916:TRPV Cation Channels; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism
chemical_list: D000700:Analgesics; D000813:Anilides; D002934:Cinnamates; D007473:Ion Channels; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D013373:Substance P; C071423:capsazepine; D002211:Capsaicin