Norepinephrine turnover and metabolism in rat brain after long-term administration of imipramine.

The rate of disappearance of intracisternally administered tritiated norepinephrine from rat brain is decreased after a single dose of the tricyclic antidepressant imipramine. During long-term administration of imipramine, however, the rate of disappearance of tritiated norepinephrine from brain gradually increases, and there is a concurrent decrease in the content of endogenous norepinephrine in brain. These findings may help to explain why antidepressant effects are observed clinically only after long-termn treatment with imipramine.