Inhibition of NaV1.7: the possibility of ideal analgesics

. 2022 Aug 1;13(8):895–920. doi: 10.1039/d2md00081d


	9: Merck⁶¹	10: AbbVie⁶³	11: Amgen⁶⁴	12: Amgen⁶⁵
hNa_V1.1 IC₅₀	—	—	—	—
hNa_V1.5 IC₅₀	17.9 μM^e^,^j	>33 μM^b^,^c	3.9 μM^b^,^c	0.95 μM^b^,^c
hNa_V1.7 IC₅₀	0.69 μM^e^,^j	0.34 μM^c^,^e	0.15 μM^b^,^k	0.37 μM^b^,^k
Rodent Na_V1.7 IC₅₀	—	—	0.049 μM (rat)^b^,^k	0.46 μM (mouse)^b^,^k
Rodent PPB^f	99% (rat)	—	82.2% (rat)	96.3% (mouse)
Free plasma concentration	0.72 μM@in vivo EC₅₀ (rat SNL)	5.7 μM@in vivo EC₅₀ (acute, rat MIA)^h	61, 280 nM@30, 100 mg kg⁻¹ (rat formalin)	0.82 μM@300 mg kg⁻¹ (mouse histamine)
Free plasma concentration	0.72 μM@in vivo EC₅₀ (rat SNL)	1.8 μM@in vivo EC₅₀ (subchronic, rat MIA)^h	61, 280 nM@30, 100 mg kg⁻¹ (rat formalin)	0.82 μM@300 mg kg⁻¹ (mouse histamine)
Na_V1.7 coverage in plasma@efficacious dosage^a	—	—	>5.7-Fold@100 mg kg⁻¹ (rat formalin)	1.8-Fold@300 mg kg⁻¹ (mouse histamine)