Are metabolites of l-deprenyl (selegiline) useful or harmful? Indications from preclinical research.

A frequent topic of controversy has been whether metabolism of l-deprenyl (selegiline) to active metabolites is a detriment to clinical use. This paper reviews possible roles of the metabolites of l-deprenyl in producing unwanted adverse side effects or in augmenting or mediating its clinically useful actions. Levels of l-amphetamine and l-methamphetamine likely to be reached, even with excessive intake of l-deprenyl, would be unlikely to produce neurotoxicity and there is no preclinical or clinical evidence of abuse liability of l-deprenyl. In contrast, there is evidence that l-amphetamine and l-methamphetamine have some qualitatively different actions than their d-isomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.