A-317491 (ABT-202) is a non-nucleotide antagonist of P2X3 and P2X2/3 receptor activation. A-317491 potently blocked recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and was highly selective (IC50 >10 uM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 also blocked native P2X3 and P2X2/3 receptors in rat dorsal root ganglion neurons. Blockade of P2X3 containing channels was stereospecific because the R-enantiomer (A-317344) of A-317491 was significantly less active at P2X3 and P2X2/3 receptors. A-317491 dose-dependently (ED50 = 30 umolkg s.c.) reduced complete Freund's adjuvant-induced thermal hyperalgesia in the rat. Studies indicate that the P2X3 receptor is implicated in both neuropathic and inflammatory pain. P2X3 receptor is a promising target for therapeutic intervention in cancer patients for pain management. ABT-202 had been in phase I clinical trials by Abbott and NeuroSearch for the treatment of pain. However, this research has been discontinued.