Evidence for a common site of action of lidocaine and carbamazepine in voltage-dependent sodium channels.
The finding that the development of lidocaine-kindled seizures is blocked by carbamazepine suggests an interaction of carbamazepine with local anesthetic mechanisms. To study the site of interaction, the effects of lidocaine, carbamazepine and another anticonvulsant drug, phenytoin on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate to the sodium channel gating complex were examined in vitro in a rat brain hippocampus preparation. Lidocaine shifted the concentration inhibition curve of carbamazepine to the right and vice versa. Carbamazepine shifted the concentration inhibition curve of phenytoin to the right and vice versa. The experimentally determined apparent dissociation constants were in a good agreement with the dissociation constants calculated for a one-site model, suggesting that the interaction occurs because lidocaine shares a common binding site with carbamazepine and phenytoin in the voltage-dependent sodium channels.
Zimányi
I
I
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, New York, NY 10035.
Weiss
S R
SR
Lajtha
A
A
Post
R M
RM
Reith
M E
ME
D000818:Animals; D001496:Batrachotoxins / Q000378:metabolism; D002220:Carbamazepine / Q000494:pharmacology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D015222:Sodium Channels / Q000187:drug effects*
D001496:Batrachotoxins; D015222:Sodium Channels; D002220:Carbamazepine; D010672:Phenytoin; D008012:Lidocaine