The use of the synthetic enhancer substances (-)-deprenyl and (-)-BPAP in major depression.

There is still a great need for the development of antidepressants with a new pharmacological spectrum. The finding that phenylethylamine and tryptamine are endogenous enhancers of the impulse propagation mediated release of catecholamines and serotonin in the brain, and the development of synthetic mesencephalic enhancer substances opened the possibility to stimulate catecholaminergic and serotonergic neurons in the mesencephalon via a previously unknown mechanism. (-)-Deprenyl, a prototype of the phenylethylamine-derived synthetic enhancer substances, stimulates the catecholaminergic neurons in the brain but is almost ineffective on the serotonergic neurons. R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, (-)-BPAP, the recently developed tryptamine-derived selective synthetic mesencephalic enhancer substance, a hundred times more potent compound than (-)-deprenyl, acts also on the serotonergic neurons. The evaluation of the special pharmacological profile of the synthetic mesencephalic enhancer substance, especially the high potency and the unusual safety and tolerability of (-)-BPAP provide hope that this compound may in the future significantly improve the effectiveness of drug therapy in major depression and its combination with uptake inhibitors may substantially diminish the number of therapy resistant cases.