Neurochemical and neuropharmacological investigations into the mechanisms of action of bupropion . HCl--a new atypical antidepressant agent.

In the present study, bupropion has been shown to be effective in several behavioral models predictive of antidepressant activity suggesting that it should be an effective antidepressant in man. Furthermore, the data also show that the antidepressant activity of the drug cannot be due to its ability to inhibit MAO present in brain or to increase the release of biogenic amines from nerve endings. It also appears unlikely that the weak properties of the drug as an inhibitor of catecholaminergic pumps in brain csn explain its antidepressant activity. However, the weak but selective block of dopaminergic pumps observed in vivo can be correlated with the mild CNS stimulant properties observed in rodents. Bupropion, failed to desensitize beta-adrenergic receptors in rat cerebral cortex in chronic studies and exhibited equivocal results in acute studies. These neurochemical properties of bupropion serve to distinguish it from typical antidepressants of the MAOI and tricyclic classes and suggest that it should be classified as an atypical antidepressant, whose mechanism of action must still be elucidated.