INHIBITION OF BIOGENIC-AMINES UPTAKE BY IMIPRAMINE, DESIPRAMINE, 2-OH-IMIPRAMINE AND 2-OH-DESIPRAMINE IN RAT-BRAIN

The tricyclic antidepressant imipramine and its metabolites desipramine, 2-hydroxyimipramine and 2-hydroxydesipramine are all pharmacologically active in the central nervous system as determined by in vitro inhibition of biogenic amine uptake by rat brain synaptosomes and their in vivo effect on spontaneous and forced motor activity. Since in vivo hydroxylation of both imipramine and desipramine produced compounds of similar pharmacological activity as the parent compounds, these results suggest that clinical studies relating plasma levels of tricyclic antidepressants to efficacy should also take into consideration the levels of hydroxylated metabolites. © 1979.