Effects of ifenprodil on voltage-gated tetrodotoxin-resistant Na+ channels in rat sensory neurons.
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.
Tanahashi
S
S
Gifu University Graduate School of Medicine, Department of Anesthesiology and Pain Medicine, Gifu City, Gifu, Japan.
Iida
H
H
Oda
A
A
Osawa
Y
Y
Uchida
M
M
Dohi
S
S
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D015640:Ion Channel Gating; D007649:Ketamine / Q000494:pharmacology; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D000779:Anesthetics, Local; D010880:Piperidines; D015222:Sodium Channels; D013779:Tetrodotoxin; D007649:Ketamine; D008012:Lidocaine; C010739:ifenprodil