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.
Yasar
S
S
Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Medical School, Baltimore, MD, USA.
Goldberg
J P
JP
Goldberg
S R
SR
D000661:Amphetamine / Q000009:adverse effects* / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D003042:Cocaine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects; D003216:Conditioning, Operant; D004353:Drug Evaluation, Preclinical; D004569:Electroencephalography; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects* / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D018696:Neuroprotective Agents / Q000009:adverse effects / Q000493:pharmacokinetics*; D018697:Nootropic Agents / Q000009:adverse effects / Q000493:pharmacokinetics; D010627:Phenethylamines / Q000008:administration & dosage; D051381:Rats; D011916:Rats, Inbred F344; D012054:Reinforcement, Psychology; D012453:Saimiri; D012642:Selegiline / Q000009:adverse effects / Q000493:pharmacokinetics*; D012646:Self Administration
D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010627:Phenethylamines; D012642:Selegiline; C029261:phenethylamine; D008694:Methamphetamine; D000661:Amphetamine; D003042:Cocaine