SB705498 is a TRPV1 antagonist for hTRPV1. SB-705498 has been investigated for the treatment of Rhinitis, Chronic Cough, and Non-allergic Rhinitis.

SB705498 (0.3 nM-1 μM) effectively blocks capsaicin-induced activation of human TRPV1 channels in 1321N1 and HEK293 cells, showing substantial inhibition potency with apparent pKi values of 7.5 and 7.6, respectively. A coapplication of 100 nM SB705498 achieves rapid, complete, and reversible suppression of hTRPV1 in HEK293 cells. This compound does not significantly impact the [Ca2+] responses in HEK293 cells induced by carbachol activation of muscarinic acetylcholine receptors or Ca2+ entry through store-operated channels following thapsigargin-mediated intracellular Ca2+ store depletion. Furthermore, SB705498 demonstrates negligible antagonistic effects on TRPV4 activation in HEK293 cells, even at concentrations ranging from 10 pM to 1 μM. Its antagonist activity remains selective for TRPV1, with notable potency against both rat and guinea pig variants, supported by pKi values of 7.5 and 7.3, respectively. Application of SB705498 at concentrations between 100 nM and 10 μM to sustained capsaicin responses enables quick and complete inhibition of hTRPV1 at -70 mV. It inhibits capsaicin-activated hTRPV1 with IC50 values of 3 nM and 17 nM at -70 mV and +70 mV, respectively. Additionally, 1 μM SB705498 can fully and reversibly inhibit TRPV1-mediated conductance when applied during the response plateau. SB705498 uniformly blocks both chemical and physical modes of TRPV1 activation and displays minimal to no activity against a broad spectrum of other ion channels, receptors, and enzymes, effectively blocking TRPV1 activation by heat and altered pH levels.

SB705498 demonstrates potent and reversible inhibition of TRPV1 receptor activation through various modes, including vanilloid (capsaicin), heat, and acid mediation. It shows remarkable efficacy at 10 and 30 mg/kg orally, effectively reversing allodynia. Additionally, SB705498 achieves an 80% reduction in allodynia within the guinea pig FCA model at a dosage of 10 mg/kg orally [2].