A-317491 is a potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors with Ki values of 22 nM and 9 nM for human P2X3 and P2X2/3 receptors.
A-317491 exhibits high efficacy and selectivity as a non-nucleotide P2X3 and P2X2/3 receptor blocker, presenting Kis of 22, 22, 9, and 92 nM against hP2X3, rP2X3, hP2X2/3, and rP2X2/3, respectively. Its selective action (IC50>10 μM) spans beyond other P2 receptors and a range of neurotransmitter receptors, ion channels, and enzymes, mitigating inflammatory and neuropathic pain by obstructing P2X3 and P2X2/3 receptor-mediated calcium movement .
体内研究
Given as a single subcutaneous injection ranging from 0.1 to 30 mg/kg, it systematically alleviates inflammatory mechanical sensitivity in rats .
Administered intravenously at doses between 3 and 30 mg/kg, A-317491 displays a half-life of 7.38 hours, a clearance rate of 1.83 L/h/kg, and a distribution volume of 0.17 L/kg .
体外研究
A-317491 effectively inhibits calcium movement through recombinant human and rat P2X3 and P2X2/3 receptors with a Ki range of 22-92 nM .
Administered at concentrations between 1 nM and 10 μM, it progressively obstructs DRG currents, evidenced by an IC50 of 15 nM .
作用机制
A-317491 is a competitive antagonist which can stabilize the apo/resting state of P2X3.[2][3]
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