Deprenyl effects on levodopa pharmacodynamics, mood, and free radical scavenging

Abstract

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.

The antiparkinson efficacy of deprenyl derives from transient improvement that is likely to be symptomatic

“…In contrast, and in support of our general conclusion, Baronti and colleagues [19] recently analyzed a series of indices of free radical activity. They assayed blood and cerebrospinal fluid of patients with idiopathic parkinsonism receiving deprenyl or placebo.…”

Antidepressant studies in Parkinson's disease: A review and meta‐analysis

“…Between 1 January 1965 and 31 December 2003, a total of 27 studies were identified5, 14, 30–54 that met inclusion criteria. Although the examined timeframe was 37 years, half (14/27, 51.9%) of the studies had been published in the past seven years 5, 14, 32, 34, 36–38, 41, 47, 48, 50–52, 54…”

Stopping selegiline may lead to problems for patients

“…Selegiline has been shown to have prolonged effect on brain function after withdrawal,4 perhaps because of its ability to inhibit monoamine oxidase B irreversibly and because of the 30 day half life for enzyme turnover 5. Thus more of the 10 other patients who reported no decline in their condition may subsequently deteriorate.…”