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N-methylpropargylamine-1-aminoindane (J-508), a strong releaser of catecholamines was described 30 years ago as a more potent selective inhibitor of MAO-B than (-)-deprenyl (Knoll 1978). In 2007 the desmethyl-analogue of J-508 (rasagiline) was registered as a new selective inhibitor of MAO-B and a possible substitute for (-)-deprenyl in therapy. The discovery of the enhancer regulation, the realization that catecholaminergic and serotonergic neurons in the brain stem are enhancer-sensitive neurons, phenylethylamine (PEA) and triptamine are endogenous enhancer substances, (-)-deprenyl is a PEA-derived synthetic enhancer substance, and finally the development of (-)-BPAP, a tryptamine-derived, 100 times more potent synthetic enhancer substance than (-)-deprenyl, made it clear that the enhancer effect of (-)-deprenyl is primarily responsible for the therapeutic benefits of this drug. To compare the pharmacological spectrum of (-)-deprenyl and rasagiline was the aim of this study. The ability of rats to acquire a two way conditioned avoidance response (CAR) in the shuttle box was analyzed during 5 consecutive days. Tetrabenazine treatment (1 mg/kg, s.c.) depletes from their stores the transmitters of the catecholaminergic neurons of the brain stem. Since the activation of the cortical neurons via the noradrenergic neurons in the brain stem is sine qua non for the acquisition for a CAR, rats treated with tetrabenazine are unable to learn in the shuttle box. To block the activity of MAO-A (clorgyline) or to treat rats with an enhancer substance [(-)-BPAP] are the two possibilities to antagonize the learning deficit caused by tetrabenazine. We compared in shuttle box experiments the effect of (-)-deprenyl, (-)-desmethyl-deprenyl, J-508 and desmethyl-J-508 (rasagiline) on the learning ability of rats pretreated with tetrabenazine. We used as a reference substance clorgyline to demonstrate the effect of a selective MAO-A inhibitor, and (-)-BPAP to demonstrate the effect of a selective enhancer substance. (-)-Deprenyl and (-)-desmethyl-deprenyl acted, like (-)-BPAP, in low doses as enhancer substances and in very high doses as MAO-A inhibitors. J-508 and rasagiline proved to be devoid of the enhancer property and in doses which are known to block MAO-A, they antagonized the effect of tetrabenazine, like clorgyline. Thus, rasagiline can not be a substitute for (-)-deprenyl in therapy.