Differential binding of antidepressants to noradrenaline and serotonin transport sites in central nerve endings.

Imipramine and mianserin are equipotent inhibitors of noradrenaline (NA) uptake in synaptosomes. However, after in vivo administration, NA uptake was inhibited only in synaptosomes from imipramine-treated rats, suggesting that imipramine, or its metabolite desipramine, binds to the NA carrier in a manner outlasting the preparation of synaptosomes, whereas mianserin is washed away. To evaluate binding to the NA carrier, synaptosomes prelabeled with 3H-NA were pretreated with an antidepressant and the release of 3H-NA was then stimulated with unlabeled NA. Any reduction of release was taken as an indication of binding. Pretreatment with desipramine, but not with imipramine or mianserin, reduced 3H-NA release suggesting that desipramine is responsible for NA uptake inhibition in synaptosomes from imipramine-treated rats. Transformation of tertiary into secondary amines seems to be crucial for binding to the NA carrier, as confirmed by the stronger binding of nortriptyline and chlordesipramine compared to amitryptiline and chlorimipramine, respectively. In contrast, tertiary amines bound more strongly than secondary amines to the serotonin carrier. Adult and 8-day old synaptosomes showed similar binding properties towards imipramine and desipraine.