BIOCHEMICAL CHARACTERISTICS OF A POTENTIAL ANTI-DEPRESSANT, 2-(7-INDENYLOXYMETHYL)MORPHOLINE HYDROCHLORIDE (YM-08054-1)

The effects of potential antidepressant, 2-(7-indenyloxymethyl)morpholine hydrochloride (YM-08054-1), on uptake, release and oxidative deamination of catecholamines and serotonin [5-hydroxytryptamine(5-HT)] were studied in vitro with rat brain, and compared with the effects of several tricyclic antidepressants and viloxazine a structural analogue of YM-08054-1. YM-08054-1 at concentrations of less than 1 μM. considerably inhibited 5-HT uptake by synaptosomes from rat whole brain as well as noradrenaline (NA) uptake by synaptosomes from rat hippocampus, similar to amitriptyline. Viloxazine and iprindole were weak inhibitors in both uptake reactions. In the release of either [14C] -5-HT from [14C]-5-HT-prelabeled hypothalamic slices or [14C]NA from [14C] NA-prelabeled hippocampal slices, YM-08054-1 and amitriptyline were much less potent than such typical potent releasers as methamphetamine and tyramine. YM-08054-1 was also found to be a weak inhibitor of both type A and type B monoamine oxidases, whereas the tricyclic antidepressants preferentially inhibited the type B enzyme. These biochemical results indicate that YM-08054-1 may be an amitriptyline-like antidepressant, but distinct from viloxazine. © 1979.