Influence of proadifen, an inhibitor of the metabolism of drugs, on the action of imipramine and desipramine in rats.

The influence of proadifen (SKF-525-A), an agent inhibiting the metabolism of drugs, on the antidepressant action of imipramine (IMI) and desipramine (DMI) in rats was investigated. Proadifen antagonized the action of IMI when investigated in reserpine hypothermia and ptosis and in the behavioral despair test. The action of DMI in the same tests was not changed by proadifen. Proadifen lowered the level of DMI and increased the level of IMI in rat brains. The results permit to draw the conclusion that DMI plays an essential role in the action arising from IMI administration, that is, the noradrenergic--and not the serotonergic--mechanism is of essential importance.