Effects of calcium antagonists on central actions of ethanol: comparative studies with nifedipine, verapamil and cinnarizine.

The effects of nifedipine (17.5 and 50 mg/kg), verapamil (5 and 15 mg/kg) and cinnarizine (75 and 200 mg/kg) on acute toxicity and central actions of ethanol (i.e. ethanol-induced sleep and hypothermia, disturbances of rota-rod performance and spontaneous activity) were investigated in mice. Additionally, effects of these drugs on the development of tolerance to hypothermic and sleep-inducing action of ethanol were studied in rats. Calcium antagonists were given acutely 30 min before ethanol administration, or chronically once daily (lower dose) for 10 days, and on the 11th day the animals received an ethanol injection. Single doses of nifedipine increased the acute toxicity of ethanol and potentiated its central effects. After long-term administration of nifedipine no significant alterations in the central actions of ethanol were observed. Verapamil and cinnarizine antagonized the ethanol-induced sleep and impairment of locomotor activity. Nifedipine did not affect the development of tolerance to hypnotic and hypothermic action of ethanol. Verapamil prevents the development of tolerance to hypnotic action of ethanol, whereas cinnarizine prevents the development of tolerance to the hypnotic and hypothermic action of ethanol.