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    InvivoChem Cat #: V1649
    CAS #: 944261-79-4Purity ≥98%

    Description: A-803467 is a novel, potent and selective NaV1.8 sodium channel blocker with IC50 of 8 nM, it is >100-fold more selective vs. human Nav1.2, 1.3, 1.5 and 1.7. with IC50 values of 8, 2450, 6740, 7340 and 7380 nM for hNaV1.8, hNaV1.3, hNaV1.7, hNaV1.5 and hNaV1.2 channels respectively. A-803467 affects multiple biophysical characteristics of the canonical cardiac Nav1.5 channel and our data can be used to study potential applications of A-803467 as an antiarrhythmic drug. A-803467 attenuates spinal neuronal activity in neuropathic rats. A-803467 also attenuates neuropathic and inflammatory pain in the rat. 

    References: Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5; J Pain. 2009 Mar;10(3):306-15. 

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    Molecular Weight (MW)357.79
    CAS No.944261-79-4
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 72 mg/mL (201.2 mM)
    Water:<1 mg/mL
    Ethanol: 11 mg/mL (30.7 mM)
    Solubility (In vivo)30% PEG400+0.5% Tween80+5% Propylene glycol: 30 mg/mL 
    SynonymsA-803467; A 803467; A803467

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    In Vitro

    In vitro activity: A-803467 potently blocks recombinant human or rat NaV1.8 channels with IC50 of 8 nM and 45 nM, respectively, at a holding potential of -40 mV. At a resting state, A-803467 also potently blocks human NaV1.8 channels with IC50 of 79 nM. A-803467 blocks tetrodotoxin-resistant (TTX-R) currents in rat dorsal root ganglion neurons in a concentration-dependent manner with IC50 of 140 nM, more potently compared with both mexiletine and lamotrigine with IC50 of >30 μM. A-803467 displays 300- to 1,000-fold higher selectivity for hNaV1.8 over hNaV1.2, hNaV1.3, hNaV1.5, and hNaV1.7 channels with IC50 of 7.38 μM, 2.45 μM, 7.34 μM, and 6.74 μM, respectively. A-803467 shows no significant activity against other channels and receptors expressed in peripheral sensory neurons including TRPV1, P2X2/3, CaV2.2 and KCNQ2/3 channels with IC50 >10 μM. A-803467 also shows no or weak activity against a broad screening panel of cell-surface receptors, ion channels, and enzymes with IC50 of >2 μM. A-803467 at 0.3 μM but not 0.1 μM significantly inhibits the generation of spontaneous and electrically evoked action potentials.

    In VivoConsistent with its effects on neuronal action potential electrogenesis in vitro, systemic administration of A-803467 (20 mg/kg, i.v.) to spinal nerve ligated rats, significantly reduces both spontaneous and von Frey hairevoked firing of spinal dorsal horn wide dynamic range neurons by 66% and 53%, respectively, compared with baseline levels. Administration of A-803467 also dose-dependently reduces mechanical allodynia in a variety of rat pain models including spinal nerve ligation (ED50 = 47 mg/kg, i.p.), sciatic nerve injury (ED50 = 85 mg/kg, i.p.), capsaicin-induced secondary mechanical allodynia (ED50 ≈ 100 mg/kg, i.p.), and thermal hyperalgesia after intraplantar complete Freund's adjuvant injection (ED50 = 41 mg/kg, i.p.). A-803467 is inactive against formalin-induced nociception and acute thermal and postoperative pain, as well as in a chemotherapy-induced pain model (vincristine).  
    Animal modelMale Sprague–Dawley rats subjected to spinal nerve ligation, sciatic nerve injury, capsaicin-induced secondary mechanical allodynia, or thermal hyperalgesia after intraplantar complete Freund's adjuvant injection, and male CD1 mice subjected to the abdominal 
    Formulation & DosageDissolved in 5% DMSO/95% polyethylene glycol (PEG 400); 100 mg/kg; i.p. injection
    ReferencesProc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5: J Pain. 2009 Mar;10(3):306-15.  

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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