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.