Interactions between diltiazem and ethanol: differences from those seen with dihydropyridine calcium channel antagonists

It has previously been shown that dihydropyridine calcium channel antagonists prevent the ethanol withdrawal syndrome and potentiate the acute effects of ethanol and other central depressant drugs. We now report that, in contrast, the benzothiazepine calcium channel antagonist, diltiazem, gave no protection against the behavioural hyperexcitability seen during ethanol withdrawal, when given either acutely, on withdrawal, or chronically, during the ethanol treatment. A significant increase in convulsive behaviour on handling was seen during the withdrawal period when diltiazem was given on cessation of a mild chronic ethanol treatment schedule. Diltiazem decreased the acute general anaesthetic effects of ethanol, and did not appear to potentiate the ataxic action of ethanol. Centrally administered diltiazem did not enhance the hypothermic action of ethanol, but this effect was significantly increased by diltiazem when the calcium channel antagonist was given peripherally. When given alone by the intraperitoneal route, diltiazem decreased spontaneous locomotor activity and lowered body temperature. When the intracerebral route was used for administration of diltiazem, a significantly decrease in body temperature was seen when this compound was given alone, accompanied by a brief hyperexcitability. The interactions between ethanol and diltiazem therefore appear to differ from those seen with other calcium channel antagonists.