A-317491

A-317491 is a potent, selective and non-nucleotide antagonist of P2X₃ and P2X_2/3 receptors, with K_is of 22, 22, 9, and 92 nM for hP2X₃, rP2X₃, hP2X_2/3, and rP2X_2/3, respectively. A-317491 is highly selective (IC50>10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 reduces inflammatory and neuropathic pain by blocking P2X₃ and P2X_2/3 receptor-mediated calcium flux^[1][2]. IC50 & Target: Ki: 22 nM (hP2X3), 22 nM (rP2X3), 9 nM (hP2X2/3), 92 nM (rP2X2/3)^[1] In Vitro: A-317491 potently blocks recombinant human and rat P2X₃ and P2X_2/3 receptor-mediated calcium flux (K_i=22-92 nM) ^[1].
A-317491 (1 nM-10 μM) produces a concentration-dependent block of dorsal root ganglion (DRG) currents with an IC₅₀ of 15 nM^[1]. In Vivo: A-317491 (0.1-30 mg/kg; a single s.c.) dose-dependently reverses inflammatory mechanical hyperalgesia in rats^[2].
A-317491 (3-30 mg/kg; a single .v.) exhibits the plasma half-life (7.38 h), clearance rate (1.83 L/h/kg), and volume of distribution (0.17 L/kg)^[2].