Differing acute interactions of ethanol with two structurally related dihydropyridines, nitrendipine and felodipine.
Previous work showed that while several dihydropyridine calcium channel antagonists have protective effects against the ethanol withdrawal syndrome, felodipine 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 acute effects of ethanol, with those of nitrendipine, a dihydropyridine previously shown to be effective against the ethanol withdrawal syndrome. Comparison 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 general anesthetic effects of ethanol, but was considerably less effective in this respect than nitrendipine. Some potentiation of the ataxic effect of ethanol was seen after concurrent administration of felodipine, but this was less than that seen after nitrendipine. In the locomotor studies, both felodipine and nitrendipine significantly decreased the locomotor stimulation produced by ethanol; the effects of the two compounds were similar, but dose-dependency was not seen at the doses tested. Chronic administration of felodipine for 2 weeks did not produce tolerance to the sedative effect of felodipine 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 administration of nitrendipine or vehicle. The results, therefore, suggest that felodipine was considerably less effective in potentiating the acute effects of ethanol than nitrendipine at doses that were equi-effective in displacing central dihydropyridine binding. The interactions of these two calcium channel antagonists with ethanol, therefore, did not parallel their effects on central dihydropyridine binding.
Watson
W P
WP
ReNeuron Ltd., Institute of Psychiatry, London, United Kingdom.
Homewood
N
N
Little
H J
HJ
D000768:Anesthesia, General; D000818:Animals; D001259:Ataxia / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D015736:Felodipine / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009568:Nitrendipine / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D002121:Calcium Channel Blockers; D000431:Ethanol; D009568:Nitrendipine; D015736:Felodipine