Induction of hypersensitivity of brain by hydralazine treatment in rats.

Pretreatment with hydralazine caused prolongation of hypnosis induced by hexobarbital (80 mg/kg, i.p.) or intracerebroventricular injection of phenobarbital (1 mg/rat). Under the same condition, brain concentration of hexobarbital was lower than that of no hydralazine treatment. In addition, no appreciable change in liver microsomal drug metabolizing enzyme activities of rats after hydralazine treatment was observed. These findings strongly suggested that hydralazine increases the sensitivity of brain to barbiturates, which leads to prolongation of sleeping time without inhibition of drug metabolizing enzymes.