Essential difference between the pharmacological spectrum of (-)-deprenyl and rasagiline

Background: (-)-Deprenyl and rasagiline are classified as selective inhibitors of B-type MAO. The DATATOP study revealed that the administration of (-)-deprenyl to untreated patients with Parkinson's disease (PD) significantly delays the need for levodopa therapy (Parkinson Study Group, 1989). Rasagiline was ineffective in this respect (Parkinson Study Group, 2002). The aim of this paper is to explain the reasoning behind the differentiation between (-)-deprenyl and rasagiline. Methods: In the shuttle box the acquisition of a two way conditioned avoidance response (CAR) was analyzed on male Wistar rats during 5 consecutive days. Tetrabenazine-treatment (1 mg/kg Sc) depletes the transmitters from their stores in the nerve terminals of the catecholaminergic neurons and blocks the acquisition of a CAR. Catecholaminergic activity enhancer (CAE) substances [(-)-deprenyl, (-)-BPAP] fully antagonize the tetrabenazine-induced learning deficit. Using (-)-deprenyl and (-)-BPAP as reference substances, we measured the effect of rasagiline and J-508 in this test. Rasagiline is the desmethyl-analog of J-508, described by Knoll in 1978. Results: In contrast to (-)-deprenyl and (-)-BPAP, J-508 and rasagiline were found in the shuttle box test to be devoid of the CAE effect. Conclusions: Since convincing experimental and clinical evidence speaks in favor for the conclusion that the catecholaminergic activity enhancer (CAE) effect of (-)-deprenyl is responsible for the significantly delayed need for levodopa therapy in untreated patients with PD (Knoll, 2012) and rasagiline is devoid of the CAE effect, this might explain why ...based on current evidence, rasagiline cannot be said to definitely have a disease-modifying effect [Robottom, 2011]. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban &Partner Sp. z o.o. All rights reserved.