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-amphctamine 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 disomer counterparts on EEG and cognitive functioning which might result in beneficial clinical effects and complement beneficial clinical actions of l-deprenyl itself.
KeywordsDiscriminative Stimulus Theta Rhythm Discriminative Stimulus Effect Abuse Liability Psychomotor Stimulant
Unable to display preview. Download preview PDF.
- Bartus RT (1990) Drugs to treat age-related neurodegenerative problems. J Aging Geriatr Sci 38: 680–695Google Scholar
- Goldberg SR, Stolerman IP (eds) (1986) Behavioral analysis of drug dependence. Academic Press, LondonGoogle Scholar
- Lynch G, Kessler M, Arai A, Larson J (1990) The nature and causes of hippocampal long-term potentiation. In: Storm-Mathisen J, Zimmer J, Ottersen OP (eds) Progress in brain research, vol 83. Elsevier Science, New York, pp 233–248Google Scholar
- Masand P, Murray GB, Pickett P (1991) Psychostimulants in post-stroke depression. J Neuropsychiatr Clin Neurosci 3: 23–27Google Scholar
- Miller R (1991) Cortico-hippocampal interplay and the representation of contexts in the brain. Springer, Berlin Heidelberg New York Tokyo (Studies of Brain Function, vol 7)Google Scholar
- Moser PC (1990) Generalization of L-deprenyl, but not MDL-72974, to the D-amphetamine stimulus in rats. Psychopharmacology 101: S40Google Scholar
- Philips SR (1981) Amphetamine, p-hydroxyamphetamine and β-phenylethylamine in mouse brain and urine after (−)-and (+)-deprenyl administration. Pharm Pharmacol 33: 739–741Google Scholar
- Tatton WG (1993) “Trophic-like” reduction of nerve cell death by deprenyl without monoamine oxidase inhibition. Neurology Forum 4: 3–10Google Scholar
- Terrace HS (1966) Stimulus control. In: Honig WK (ed) Operant behavior: areas of research and application. Prentice-Hall, Englewoods Cliffs NJ, pp 271–344Google Scholar
- Yasar S, Winger G, Nickel B, Schulze G, Goldberg SR (1993b) Preclinical evalation of l-deprenyl: lack of amphetamine-like abuse potential. In: Szelenyi I (ed) Inhibitors of monoamine oxidase B. Birkhäuser, Basel, pp 215–233Google Scholar