POTENTIAL ANTIDEPRESSIVE PROPERTIES OF AMANTADINE, MEMANTINE AND BIFEMELANE

The effects of amantadine, its dimethyl derivative, memantine and the chemically unrelated compound bifemelane were tested for antidepressan t activity. Reserpine-induced hypothermia and the forced swim test (Po rsolt test) were selected for this purpose. In the former test amantad ine and bifemelane but not memantine were effective. In the forced swi m test all three agents produced antidepressive-like activity (decreas ed immobility time), but in case of bifemelane it was less pronounced. The effect in the forced swim test was specific i.e. it was apparentl y not the result of an increase in general activity as evidenced by co ntrol experiments in the open field. The mechanism of amantadine and m emantine action may involve indirect dopaminomimetic activity resultin g from the blockade of NMDA receptors. However in reserpine-induced hy pothermia this explanation is not valid considering the lack of effect of memantine and positive action of amantadine. Hence, amantadine may have an additional central sympathomimetic action that memantine is l acking. Bifemelane antidepressant-like activity might be attributed to an enhancement of noradrenergic transmission. We suggested that amant adine and bifemelane could be particularly useful therapeutically when depressive symptoms are present in patients suffering from Parkinson' s disease and dementia.