Cell lines

Rat dorsal root ganglion (DRG) neurons and HEK-293 cells expressing human Nav1.8 sodium channels

Preparation method

The solubility of this compound in DMSO is >13.95 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20 ℃ for several months.

Reacting condition

0 ~ 100 μM

Applications

A-803467 at the dose of 100 nM significantly blocks recombinant human and native rat Nav1.8 currents. In rat DRG neurons, A-803467 concentration-dependently blocked tetrodotoxin-resistant (TTX-R) current at the potential of -40 mV, with the IC50 value of 140 nM.

Animal models

Spinal nerve ligated rats

Dosage form

20 mg/kg; i.v.

Applications

In spinal nerve ligated rats, A-803467 markedly reduced spontaneous and von Frey hair evoked firing of spinal dorsal horn wide dynamic range neurons by 66% and 53%, respectively, which implied that systemic administration of A-803467 altered the activity of spinal sensory neurons. In addition, these effects of A-803467 were dose-dependent.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

A-803467 is a potent and selective blocker of Nav1.8 sodium channel with IC50 value of 8nM [1].

A-803467 is a sodium channel blocker with high affinity and selectivity. It blocks the human Nav1.8 channels with IC50 value of 79nM. It also blocks the recombinant rat Nav1.8 channels with IC50 value of 45nM when the holding potential is -40mV. A-803467 is highly selective against Nav1.8 since the inhibition of Nav1.8 is 300- to 1000-fold more potent than of NaV1.2, NaV1.3, NaV1.5, and NaV1.7. It is found that A-803467 effectively suppresses the evoked and spontaneous action potential firing in DRG neurons in which TTX-R currents play a remarkable role. Furthermore, the selective blockade of Nav1.8 channels results in a significant reduction in nociceptive sensitivity. A-803467 potently attenuates mechanical allodynia in models of neuropathic pain. It also potently reduces thermal hyperalgesia in the CFA model of inflammatory pain [1].

References:
[1] Jarvis M F, Honore P, Shieh C C, et al. A-803467, a potent and selective Nav1. 8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat. Proceedings of the National Academy of Sciences, 2007, 104(20): 8520-8525.