865305-30-2

AF-353 is a noncompetitive dual antagonist of the purinoreceptors P2X₃ and P2X_2/3 (IC₅₀s = 10 and 79.4 nM, respectively). It is selective for P2X₃ and P2X_2/3 over P2X₁, P2X₂, P2X₄, P2X₅, and P2X₇ (IC₅₀ = >10 μM for all). It inhibits calcium flux in CHO-K1 cells expressing the rat P2X₃ receptor and in 1321N1 cells expressing the human P2X₃ and P2X_2/3 receptors (IC₅₀s = 8.91, 8.71, and 38.9 nM, respectively). AF-353 decreases the electrical signals in the detrusor, but not striated, muscle of the bladder in female rats.