Effects of the novel TRPV1 receptor antagonist SB366791 in vitro and in vivo in the rat

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 500nM) 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 mu M) with an IC50 of 651.9 nM. In vivo 500 mu g/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 I It. 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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.