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 is approximately 3 fold less potent to block Na(v)1.2, approximately 10 fold less potent to block tetrodotoxin-sensitive sodium (TTX-S Na(+)) currents and is >30 fold less potent to block Na(v)1.5 channels. A-887826 potently blocks tetrodotoxin-resistant sodium (TTX-R Na(+)) currents (IC50: 8 nM) from small diameter rat dorsal root ganglion (DRG) neurons in a voltage-dependent fashion. A-887826 effectively suppresses evoked action potential firing when DRG neurons are held at depolarized potentials and reversibly suppresses spontaneous firing in small-diameter DRG neurons from complete Freund's adjuvant inflamed rats. A-887826 (100 nM) shifts the mid-point of voltage-dependent inactivation of TTX-R currents by approximately 4mV without affecting voltage-dependent activation and does not exhibit frequency-dependent inhibition.

A-887826 (3-30 mg/kg; p.o.; 1-hour pre-treatment) significantly attenuates 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