product name A-803467
Description: A-803467 is a selective NaV1.8 channel blocker with IC50 of 8 nM. 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.
357.79
Formula
C19H16ClNO4
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
Synonyms
other peoduct :
| 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. Kinase Assay: Cell Assay: |
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| In Vivo | Consistent 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 Freunds 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 model | Male Sprague–Dawley rats subjected to spinal nerve ligation, sciatic nerve injury, capsaicin-induced secondary mechanical allodynia, or thermal hyperalgesia after intraplantar complete Freunds adjuvant injection, and male CD1 mice subjected to the abdominal |
| Formulation & Dosage | Dissolved in 5% DMSO/95% polyethylene glycol (PEG 400); 100 mg/kg; i.p. injection |
| References | Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5: J Pain. 2009 Mar;10(3):306-15. |
