INTERACTIONS BETWEEN DILTIAZEM AND ETHANOL - DIFFERENCES FROM THOSE SEEN WITH DIHYDROPYRIDINE CALCIUM-CHANNEL ANTAGONISTS

It has previously been shown that dihydropyridine calcium channel anta gonists prevent the ethanol withdrawal syndrome and potentiate the acu te effects of ethanol and other central depressant drugs. We now repor t that, in contrast, the benzothiazepine calcium channel antagonist, d iltiazem, gave no protection against the behavioural hyperexcitability seen during ethanol withdrawal, when given either acutely, on withdra wal, or chronically, during the ethanol treatment. A significant incre ase in convulsive behaviour on handling was seen during the withdrawal period when diltiazem was given on cessation of a mild chronic ethano l treatment schedule. Diltiazem decreased the acute general anaestheti c effects of ethanol, and did not appear to potentiate the ataxic acti on of ethanol. Centrally administered diltiazem did not enhance the hy pothermic action of ethanol, but this effect was significantly increas ed by diltiazem when the calcium channel antagonist was given peripher ally. When given alone by the intraperitoneal route, diltiazem decreas ed spontaneous locomotor activity and lowered body temperature. When t he intracerebral route was used for adminstration of diltiazem, a sign ificantly decrease in body temperature was seen when this compound was given alone, accompanied by a brief hyperexcitability. The interactio ns between ethanol and diltiazem therefore appear to differ from those seen with other calcium channel antagonists.