Drug interactions between imipramine and benzodiazepines in rats

The concomitant administration of diazepam and imipramine hydrochloride increased desipramine concentration in rat plasma, but decreased 2-hydroxyimipramine and 2-hydroxydesipramine concentrations; the concomitant administration of oxazepam and imipramine hydrochloride decreased imipramine, 2-hydroxyimipramine, and 2-hydroxydesipramine concentrations. Imipramine plasma protein binding was unaltered in all cases. Liver concentrations of imipramine and 2-hydroxydesipramine were increased by concomitant administration of oxazepam and imipramine hydrochloride. Concomitant administration of benzodiazepines and imipramine hydrochloride increased imipramine concentration in the brain. The effects of imipramine hydrochloride on hypothermia induced by reserpine, and on behavioral despair in rats was also studied. The concomitant administration of diazepam and imipramine hydrochloride led to a decrease in the anti-reserpine effect of imipramine hydrochloride and in the imipramine hydrochloride-induced recovery from immobility in the forced swimming test. These results are in accord with the findings on brain concentrations of imipramine and its metabolites.