Calcium channel antagonists prevent adaptive responses to ethanol.

Prolonged ethanol administration causes upregulation of dihydropyridine-sensitive binding sites, thought to represent neuronal calcium channels, and these channels appear to play an important role in ethanol physical dependence. Dihydropyridine calcium channel antagonists, when given chronically with ethanol, prevent the development of tolerance to ethanol and the ethanol withdrawal syndrome. The upregulation of binding sites for these compounds was also prevented. Epileptiform activity has been described in isolated hippocampal slices after chronic ethanol treatment in vivo. This was prevented, stereoselectively, by the dihydropyridine calcium channel antagonist, isradipine, that did not affect the hyperexcitability produced in control slices by the GABAA antagonist, bicuculline.