Potentiation of ethanol via interference with calcium channels.
The relevance of ethanol's ability to inhibit voltage-gated and receptor-gated calcium ion conductance in vitro to its acute effects in intact animals was examined. Specifically, nimodipine (a voltage-sensitive calcium antagonist of the dihydropyridine class), indole-2-carboxylic acid (a competitive antagonist of the strychnine-insensitive glycine binding site), MK-801 (a noncompetitive allosteric antagonist of the NMDA receptor complex), and d-cycloserine (a partial agonist of the strychnine-insensitive glycine binding site) were examined for their ability to alter ethanol's antiseizure efficacy in an incremental electroconvulsive shock paradigm. The results showed that drugs known to interfere with voltage-gated and receptor-gated calcium ion conductance potentiated ethanol's antiseizure efficacy. These results implicate voltage-gated and receptor-gated calcium ion conductance in ethanol's acute pharmacologic effects in intact animals.
Deutsch
S I
SI
Psychiatry Service, Department of Veterans Affairs Medical Center, Washington, DC 20422.
Kaushik
M
M
Huntzinger
J A
JA
Novitzki
M R
MR
Mastropaolo
J
J
D000818:Animals; D000927:Anticonvulsants; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002264:Carboxylic Acids; D003524:Cyclosporins / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D004597:Electroshock; D000431:Ethanol / Q000494:pharmacology*; D005998:Glycine / Q000037:antagonists & inhibitors; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D009553:Nimodipine / Q000494:pharmacology
D000927:Anticonvulsants; D002121:Calcium Channel Blockers; D002264:Carboxylic Acids; D003524:Cyclosporins; D007211:Indoles; C058980:indole-2-carboxylic acid; D000431:Ethanol; D009553:Nimodipine; D016291:Dizocilpine Maleate; D005998:Glycine