The effect of phenobarbital and carbamazepine on the ethanol withdrawal reaction in the rat.

The effects of phenobarbital (PB) and carbamazepine (CZ) on the ethanol withdrawal reaction in the rat were investigated in a blind study including an untreated control group. Physical ethanol dependence was established by intragastric intubation during a 4-day period. Both the degree of intoxication and the withdrawal reaction were assessed by standardised assessment instruments. Treatment with PB (40-60 mg/kg) and CZ (80-120 mg/kg) was initiated 10 h after the last ethanol dose and continued during the first 24 h of withdrawal. Serum concentrations of the drugs were measured. Both PB and CZ significantly reduced the ethanol withdrawal reaction compared to controls, and PB was significantly more effective than CZ. The degree of drug intoxication signs assessed by the same rating scale as the degree of ethanol intoxication indicated that maximum tolerable drug doses were used. PB probably exerts its treatment effect through the mechanism of cross dependence with ethanol, while CZ may exert a more specific effect on limbic structures responsible for central nervous system excitability.