Differing acute interactions of ethanol with two structurally related dihydropyridines, nitrendipine and felodipine

Previous work showed that while several dihydropyridine calcium channel ant agonists have protective effects against the ethanol withdrawal syndrome, f elodipine differed in lacking this action. Dihydropyridine calcium channel antagonists have also been shown to potentiate the acute behavioral actions of ethanol. The present study compares the effects of felodipine on the ac ute effects of ethanol, with those of nitrendipine, a dihydropyridine previ ously shown to be effective against the ethanol withdrawal syndrome; Compar ison was made at doses of the compounds that have previously been shown to produce similar displacement of dihydropyridine binding in central nervous system (CNS) tissue. Felodipine had a small potentiating effect on the gene ral anesthetic effects of ethanol, but was considerably less effective in t his respect than nitrendipine. Some potentiation of the ataxic effect of et hanol was seen after concurrent administration of felodipine, but this was less than that seen after nitrendipine. In the locomotor studies, both felo dipine and nitrendipine significantly decreased the locomotor stimulation p roduced by ethanol; the effects of the two compounds were similar, but dose -dependency was not seen at the doses tested. Chronic administration of fel odipine for 2 weeks did not produce tolerance to the sedative effect of fel odipine or cross-tolerance to nitrendipine. After chronic administration of the felodipine, administration of an acute dose of ethanol resulted in an increase in locomotor activity, but this was not seen after chronic adminis tration of nitrendipine or vehicle. The results, therefore, suggest that fe lodipine was considerably less effective in potentiating the acute effects of ethanol than nitrendipine at doses that were equieffective in displacing central dihydropyridine binding. The interactions of these two calcium cha nnel antagonists with ethanol, therefore, did not parallel their effects on central dihydropyridine binding. (C) 1998 Elsevier Science Inc.