A-317491|cas 475205-49-3

A-317491|cas 475205-49-3

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Product Name: A-317491|CAS: 475205-49-3|Cat No: DC10643|Other Names:

A-317491 is a novel 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.

In vitro:
A-317491 potently blocks recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22-92 nM) and is highly selective (IC50 >10 μM) over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes. A-317491 does not undergo any detectable metabolism (oxidation or glucuronidation) in in vitro assays using human and rat liver microsomes.
In vivo: A-317491 dose-dependently (ED50 = 30 μmol/kg s.c.) reduces complete Freund's adjuvant-induced thermal hyperalgesia in the rat. A-317491 is most potent (ED50 = 10-15 μmol/kg s.c.) in attenuating both thermal hyperalgesia and mechanical allodynia after chronic nerve constriction injury. Although active in chronic pain models, A-317491 is ineffective (ED50 >100 μmol/kg s.c.) in reducing nociception in animal models of acute pain, postoperative pain, and visceral pain. Preliminary pharmacokinetic studies in rats indicate that 10 μmol/kg A-317491 had high (≈80%) systemic bioavailability after s.c. dosing (estimated plasma concentration = 15 μg/ml, >99% protein bound) and a half-life in plasma of 11 h. A-317491 is effective in reducing pain associated behavior in several animal models of inflammatory and neuropathic pain when administered systemically. A-317491 does not significantly penetrate into the CNS.