V116517

V116517 is a potent, orally active transient receptor potential vanilloid (TRPV1) antagonist. V116517 shows potent activity in inhibiting both capsaicin (CAP)- and acid (pH 5)-induced currents in rat DRG neurons expressing native TRPV (IC₅₀=423.2 nM for CAP; IC₅₀=180.3 nM for acid). V116517 can be used for the research of pain^[1]. IC50 & Target: TRPV1^[1] In Vitro: V116517?is highly selective for TRPV1 and did not show potency up to 10 μM in both TRPV3 and TRPV4 assays^[1].
V116517?has fast-off kinetics for antagonism of both mode activations of TRPV1^[1]. In Vivo: V116517?shows dose-dependent reversal of thermal hyperalgesia with an ED₅₀?of 2 mg/kg (PO) in complete Freund’s adjuvant (CFA) inflammatory pain model^[1].?
V116517 exhibits high oral bioavailability (rat 74%, dog 100%, monkey 107%) and Cmax?(rat 1380, dog 1120, monkey 459 ng/mL) following oral administration (rat 3, dog 3, monkey 3 mg/kg)^[1].
V116517 exhibits terminal elimination half-lives (rat 3.3, dog 3.6 and, monkey 18 h) due to high plasma clearance (0.24, 0.28, and 0.36 L/h/kg respectively) combined with large volumes of distribution (0.68, 1.2, and 6.0 L/kg respectively) following intravenous administration (rat 1, dog 1 and, monkey 1 mg/kg)^[1].
V116517 (rat 3 mg/kg; oral administration)?is primarily restricted in periphery.The ratio of brain-to-plasma concentration is 0.09 at 3 h^[1].