Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging.
Clinical evidence suggests that deprenyl may slow progression of Parkinson's disease, although mechanisms underlying this putative neuroprotective action remain poorly understood. To address this issue, we studied deprenyl in 12 parkinsonian patients using a single-blind, placebo-controlled, crossover design. After 1 month, deprenyl (10 mg/d) decreased the optimal levodopa requirement by 24% (oral) and 16% (intravenous). Levodopa-induced dyskinesias were prolonged by 430%, and antiparkinsonian action by 44%. Mood improved by 47%. One month after withdrawing deprenyl, effects on dyskinesias and mood had yet to return to baseline. There was no change in activities of circulating glutathione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase, and catalase, nor in levels of lipid peroxide and vitamin E. Deprenyl also failed to modify CSF levels of total glutathione and activities of glutathione peroxidase or superoxide dismutase. These effects on levodopa pharmacodynamics and mood complicate the interpretation of available investigations of deprenyl's neuroprotective action and increase the risk of adverse effects of levodopa.
Baronti
F
F
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.
Davis
T L
TL
Boldry
R C
RC
Mouradian
M M
MM
Chase
T N
TN
D000339:Affect / Q000187:drug effects; D000368:Aged; D002374:Catalase / Q000032:analysis; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D005979:Glutathione Peroxidase / Q000032:analysis; D005980:Glutathione Reductase / Q000032:analysis; D006801:Humans; D007980:Levodopa / Q000378:metabolism* / Q000627:therapeutic use; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D012642:Selegiline / Q000494:pharmacology* / Q000627:therapeutic use; D013482:Superoxide Dismutase / Q000032:analysis
D005609:Free Radicals; D012642:Selegiline; D007980:Levodopa; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione