Deprenyl in the treatment of Parkinson's disease: clinical effects and speculations on mechanism of action.
Selegiline is a relatively selective inhibitor of monoamine oxidase type B that has been used in Parkinson's disease as an adjunct to levodopa and as putative neuroprotective therapy. Clinical trials demonstrate that selegiline slows the rate of disease progression and delays the appearance of disability necessitating levodopa. However, confounding symptomatic effects have made it difficult to ascertain the presence of any direct neuroprotective effect. Laboratory studies demonstrate that selegiline protects dopaminergic neurons through a mechanism that does not involve MAO-B inhibition. Recent studies suggest that neuroprotection in laboratory models may be related to the capacity of selegiline to up-regulate a series of anti-oxidant and anti-apoptotic molecules which promote cell survival. Further delineation of the precise mechanism whereby selegiline induces this effect may permit for the development of enhanced neuroprotective benefits in PD patients.
Olanow
C W
CW
Mount Sinai School of Medicine, New York, NY, USA.
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002986:Clinical Trials as Topic; D004298:Dopamine / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015337:Multicenter Studies as Topic; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000188:drug therapy*; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000209:etiology; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D012642:Selegiline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D000975:Antioxidants; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D012642:Selegiline; D007980:Levodopa; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine