EVALUATION OF PHYSICAL-DEPENDENCE LIABILITY OF L-DEPRENYL (SELEGILINE) IN ANIMALS

l-Deprenyl is a useful drug that has been successful in the clinical t reatment of parkinsonism. However, l-deprenyl is a phenylalkylamine de rivative that undergoes metabolic transformation to l-methamphetamine and l-amphetamine. Therefore, the question arises whether l-deprenyl p ossesses amphetamine-like abuse liability. This article reviews a seri es of different preclinical studies in rats that used experimental pro cedures to provide preclinical information predictive of human abuse l iability. In one series we investigated whether repeated administratio n of l-deprenyl to rats resulted in observable signs of physical depen dence. In a second series of studies, the effects of l-deprenyl on the cortical electrical activity of freely moving rats were investigated. Finally, the influence of l-deprenyl on behavior of the animals was s tudied. In all studies, different stereospecific configurations of amp hetamine and deprenyl were compared. During and after 6 weeks of oral administration of l-deprenyl, no signs of physical dependence were obs erved in rats after withdrawal of the drug. In contrast, with d-depren yl, d-amphetamine, and racemic d,l-amphetamine, signs indicative of ph ysical dependence were observed after withdrawal of the drug. For exam ple, the body weight of the rats was increased. In addition, changes i n electroencephalograms and behavior of rats induced by l-deprenyl and l-amphetamine were different from those produced by the d-enantiomers . Thus preclinical results confirm the clinical experience that therap eutically relevant doses of l-deprenyl are without physical dependence liability.