Background and objective: To examine a possible mechanism for the antinociceptive action of the N-methyl-D-aspartate receptor antagonist ifenprodil, we compared its effects with those of ketamine on tetrodotoxin-resistant Na+ channels in rat dorsal root ganglion neurons, which play an important role in the nociceptive pain pathway.
Methods: Experiments were performed on dorsal root ganglion neurons from Sprague-Dawley rats, recordings of whole-cell membrane currents being made using patch-clamp technique.
Results: Both drugs blocked tetrodotoxin-resistant Na+ currents dose dependently, their half-maximal inhibitory concentrations being 145+/-12.1 micromol (ketamine) and 2.6+/-0.95 micromol (ifenprodil). Ifenprodil shifted the inactivation curve for tetrodotoxin-resistant Na+ channels in the hyperpolarizing direction and shifted the activation curve in the depolarizing direction. Use-dependent blockade of tetrodotoxin-resistant Na+ channels was more marked with ifenprodil than with ketamine. When paired with lidocaine, these drugs produced similar additive inhibitions of tetrodotoxin-resistant Na+ channel activity.
Conclusions: The observed suppressive effects on tetrodotoxin-resistant Na+ channel activity may, at least in part, underlie the antinociceptive effects of these N-methyl-D-aspartate receptor antagonists.