Effects of quinupramine on the central monoamine uptake systems and involvement of pharmacokinetics in its pharmacological activities.

The effects of a new tricyclic antidepressant drug, quinupramine, on the monoamine uptake of rat brain homogenate preparations were studied in comparison with imipramine. Pharmacokinetic studies on quinupramine and imipramine in plasma and brain were also performed in rats after a single oral administration. Quinupramine had few effects on the noradrenaline and serotonin uptake both in in vitro and ex vivo models. After the administration of [3H]quinupramine, the unchanged drug was estimated as 60-75% of the total radioactivity in the cerebral cortex. Imipramine and desipramine preferentially inhibited the uptake of serotonin and noradrenaline, respectively, in vitro. After the administration, imipramine showed a marked inhibitory effect on noradrenaline uptake. A considerable amount of desipramine but not imipramine could be detected in the brain and plasma after the administration of [3H]imipramine. These results demonstrate that 1) the antidepressant activity of quinupramine cannot be attributed to inhibition of monoamine uptake, 2) unchanged quinupramine penetrates into the CNS and affects some of the processes of neurotransmission and 3) the pharmacological activities of imipramine, when administered orally, may be attributed to desipramine, the metabolite formed.