A-803467

Biological Activity

A-803467 is a potent and selective Nav1.8 sodium channel blocker. A-803467 blocks Nav1.8 in both half-maximal inactive and resting states with an IC50 of 8 nM and IC50 of 79 nM, respectively. A-803467 is >100-fold selective vs. human Na(v)1.2, Na(v)1.3, Na(v)1.5, and Na(v)1.7 (IC50 values >or=1 microM). Administration of A-803467 (10-30 mg/kg i.v.) reduced mechanically evoked (10-g von Frey hair) and spontaneous WDR neuronal activity in SNL rats. A-803467 also dose-dependently reduced mechanical allodynia in a variety of rat pain models. A-803467 is the first small-molecule blocker of sodium channels which showing both high potency and significant subtype-selectivity among the sodium channel family.

Customer Product Validations & Biological Datas

	Source	Sci Rep (2017). Figure 6. A-803467
	Method	Measurement of LSG function
	Cell Lines	Left stellate ganglion
	Concentrations	20 mM
	Incubation Time	-
	Results	As shown in Fig. 6A, the ganglion neurons in the DMSO group were mostly stained positive for TH (red) and negative for TUNEL (green). However, in the high-concentration A-803467 treatment group, most ganglion neurons stained positive for both TH and TUNEL.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information

References

A selective Nav1.8 sodium channel blocker, A-803467 [5-(4-chlorophenyl-N-(3,5-dimethoxyphenyl)furan-2-carboxamide], attenuates spinal neuronal activity in neuropathic rats.
McGaraughty S, et al. J Pharmacol Exp Ther. 2008 Mar;324(3):1204-11. PMID: 18089840.

A-803467, a potent and selective Nav1.8 sodium channel blocker, attenuates neuropathic and inflammatory pain in the rat.
Jarvis MF, et al. Proc Natl Acad Sci U S A. 2007 May 15;104(20):8520-5. PMID: 17483457.