A-425619

A-425619 is an orally active and selective transient receptor potential type V1 (TRPV1) antagonist. A-425619 blocks Capsaicin (HY-10448)- and N-arachidonoyl-dopamine (NADA)-induced Ca²⁺ influx in dorsal root ganglia and trigeminal ganglia. A-425619 relieves pathophysiological pain associated with inflammation and tissue injury in rats. A-425619 can be used for the study of pain related to inflammation and tissue injury^[1][2][3]. In Vitro:A-425619 (10 μM) blocks 500 nM Capsaicin (HY-10448)-induced Ca²⁺ influx in dorsal root ganglia (IC₅₀ = 78 nM) and trigeminal ganglia (IC₅₀ = 115 nM), and inhibits 3 μM N-arachidonoyl-dopamine (NADA)-induced Ca²⁺ influx in dorsal root ganglia (IC₅₀ = 36 nM) and trigeminal ganglia (IC₅₀ = 37 nM)^[1].
A-425619 (100 nM) can completely inhibit TRPV1-mediated acid-activated currents in dorsal root ganglia and trigeminal ganglion neurons^[1].
A-425619 (0.01-1 μM) can significantly block 300 nM Capsaicin- and 3 μM NADA-evoked calcitonin gene-related peptide (CGRP) release in dorsal root ganglia^[1].
A-425619 (3-100 nM) potently blocks the activation of native TRPV1 channels in rat dorsal root ganglion neurons(IC₅₀ = 9 nM)^[2].
In Vivo:A-425619 (10.3-103 μg/rats (30-300 nmol/rats), intraplantar, 15 min before Capsaicin, single dose or 10.3-35 mg/kg (30-100 μmol/kg), p.o., 60 min before Capsaicin, single dose) dose-dependently blocks Capsaicin-induced mechanical hyperalgesia in rats^[3].
A-425619 (3.5-35 mg/kg (10-100 μmol/kg), i.p., 30 min before testing, single dose or 3.5-103 mg/kg (10-300 μmol/kg), p.o., 60 min before testing, single dose) dose-dependently relieves CFA-induced chronic inflammatory thermal hyperalgesia in rats^[3].
A-425619 (103 μg/rats (300 nmol/rats), intraplantar into inflamed paw, 30 min before testing, single dose) reduces CFA-induced thermal hyperalgesia in rats^[3].
A-425619 (3.5-35 mg/kg (10-100 μmol/kg), i.p., 90 min after Carrageenan (HY-125474), single dose) dose-dependently relieves Carrageenan-induced acute inflammatory thermal hyperalgesia in rats^[3].
A-425619 (35 mg/kg (100 μmol/kg), p.o., twice daily for 5 days) maintains efficacy in relieving skin incision-induced mechanical allodynia in rats^[3].
A-425619 (35-103 mg/kg (100-300 μmol/kg), i.p., 30 min before testing, single dose) reduces MIA-induced osteoarthritic pain in rats^[3].
A-425619 (35 mg/kg (100 μmol/kg), i.p., 30 min before testing, single dose) reduces mechanical allodynia in L5/L6 spinal nerve ligation model and in sciatic nerve ligation model of neuropathic pain in rats^[3].