A-317491 is a non-nucleotide antagonist of the purinergic receptors P2X3 and P2X2/3 (Kis = 22-92 nM in a calcium influx assay) that is selective over other purinergic and neurotransmitter receptors, ion channels, and enzymes (IC50s = >10 ?M).1 It reduces thermal hyperalgesia induced by complete Freund’s adjuvant in rats (ED50 = 30 ?mol/kg, s.c.) and nociceptive responses to chemically-induced pain. Chronic administration of A-317491 (30 ?mol/kg, twice daily) reduces early, but not late, phase pain in a mouse model of bone cancer.2 A-317491 does not readily cross the blood-brain barrier and reduces pain responses when applied topically in a rat model of inflammatory pain, indicating that it acts primarily at peripheral purinergic receptors.3
1.Jarvis, M.F., Burgard, E.C., McGaraughty, S., et al.A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the ratProc. Natl. Acad. Sci. USA99(26)17179-17184(2002) 2.Hansen, R.R., Nasser, A., Falk, S., et al.Chronic administration of the selective P2X3, P2X2/3 receptor antagonist, A-317491, transiently attenuates cancer-induced bone pain in miceEur. J. Pharmacol.688(1-3)27-34(2012) 3.Wu, G., Whiteside, G.T., Lee, G., et al.A-317491, a selective P2X3/P2X2/3 receptor antagonist, reverses inflammatory mechanical hyperalgesia through action at peripheral receptors in ratsEur. J. Pharmacol.504(1-2)45-53(2004)