A-887826 is a selective, orally bioavailable, and voltage-dependent Na(v1.8) channel blocker (IC50: 11 nM). It attenuates neuropathic tactile allodynia in vivo.

Nav1.8:11 nM

A-887826 exhibits variable potency in blocking sodium channels, being approximately three times less effective against Na(v)1.2 channels, about ten times less effective in blocking tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents, and over thirty times less effective against Na(v)1.5 channels. However, it demonstrates significant efficacy in blocking tetrodotoxin-resistant sodium (TTX-R Na(+)) currents with an IC50 of 8 nM in small diameter rat dorsal root ganglion (DRG) neurons, acting in a voltage-dependent manner. It potently reduces both evoked and spontaneous action potential firing in DRG neurons at depolarized potentials and in neurons from rats with inflammation due to complete Freund's adjuvant. A-887826, at a concentration of 100 nM, specifically alters the voltage-dependent inactivation of TTX-R currents by about 4mV, without impacting voltage-dependent activation, and does not show frequency-dependent inhibition.

A-887826 (3-30 mg/kg; p.o.; 1-hour pre-treatment) significantly reduces tactile allodynia in a rat neuropathic pain model.

Animal Model: Male Spraguee Dawley rats (200-300 g). Dosage: 3 mg/kg, 10 mg/kg, 30 mg/kg. Administration: p.o.; 1 hour before testing; fourteen days after L5-L6 spinal nerve ligation