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A 317491 sodium salt
Selective, high affinity non-nucleotide P2X3 and P2X2/3 receptor antagonist (Ki values are 9, 22, 22 and 92 nM at human P2X2/3, rat P2X3, human P2X3 and rat P2X2/3, respectively); blocks recombinant human and rat P2X3 and P2X2/3 receptor-mediated calcium flux (Ki = 22 - 92 nM). Exhibits selectivity over other P2 receptors and other neurotransmitter receptors, ion channels, and enzymes (IC50 > 5 μM). Reduces mechanical allodynia and thermal hyperalgesia in the CCI in vivo models. Antinociceptive.
|Storage||Store at -20°C|
The technical data provided above is for guidance only. For batch specific data refer to the Certificate of Analysis.
Tocris products are intended for laboratory research use only, unless stated otherwise.
|Solvent||Max Conc. mg/mL||Max Conc. mM|
Preparing Stock Solutions
The following data is based on the product molecular weight 609.54. Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
|Concentration / Solvent Volume / Mass||1 mg||5 mg||10 mg|
|1 mM||1.64 mL||8.2 mL||16.41 mL|
|5 mM||0.33 mL||1.64 mL||3.28 mL|
|10 mM||0.16 mL||0.82 mL||1.64 mL|
|50 mM||0.03 mL||0.16 mL||0.33 mL|
References are publications that support the biological activity of the product.
Jarvis et al (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc.Nat.Acad.Sci.USA 99 17179 PMID: 12482951
McGaraughty et al (2003) Effects of A-317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration. Br.J.Pharmacol. 140 1381 PMID: 14623769
McGaraughty et al (2005) Endogenous opioid mechanisms partially mediate P2X3/P2X2/3-related antinociception in rat models of inflammatory and chemogenic pain but not neuropathic pain. Br.J.Pharmacol. 146 180 PMID: 16041397
Mansoor et al (2016) X-ray structures define human P2X3 receptor gating cycle and antagonist action. Nature 538 66 PMID: 27626375
Neelands et al (2003) 2', 3'-O-(2,4,6,trinitrophenyl)-ATP and A-317491 are competitive antagonists at a slowly desensitizing chimeric human P2X3 receptor. Br.J.Pharmacol. 140 202 PMID: 12967950
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Literature in this Area
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Peripheral sensitization is the reduction in the threshold of excitability of sensory neurons that results in an augmented response to a given external stimulus. This poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described.