TRPV1 is a non-selective cation channel, predominantly expressed by peripheral sensory neurons. It plays a key role in the detection of noxious painful stimuli, such as capsaicin, acid and heat. SB-705498 is a potent TRPV1 antagonist with pKb value of 7.5 in FLIPR-Ca2+-based assays versus capsaicin at TRPV1. Co-application of 1μM SB-705498 completely and reversibly inhibited capsaicin-mediated activation of human TRPV1 by measure of whole cell currents by patch clamp. Pre-treatment with SB-705498 at doses of 3mg/kg and 10mg/kg, p.o., for 2h, dose-dependently antagonized capsaicin induced secondary hyperalgesia in rat. SB-705498 can potently inhibit the multiple modes of TRPV1 activation, including capsaicin-, acid- and heat-mediated activation of human TRPV1.
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