AF-353 is a novel, potent and orally bioavailable P2X3/P2X2/3 receptor antagonist, inhibits human and rat P2X3 (pIC50= 8.0). IC50 value: pIC50 = 8.0 (pIC50, for P2X3) Target: P2X3/P2X2/3 receptor in vitro: AF-353 is a highly potent inhibitor of ,-meATP-evoked intracellular calcium flux in cell lines expressing recombinant rat and human P2X3 and human P2X2/3 channels. AF-353 also blocks human P2X2/3 channel function with marginally reduced potency (pIC50 = 7.3).  in vivo: SCI rats has significantly higher frequencies for field potentials and NVC than NL rats. Intravesical ATP increases field potential frequency in control but not SCI rats, while systemic AF-353 significantly reduces this parameter in both groups. AF-353 also reduces the inter-contractile interval in control but not in SCI rats; however, the frequency of NVC in SCI rats was significantly reduced
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