LE JOURNAL CANADIEN DES SCIENCES NEUROLOGIQUES Viewpoints on Deprenyl Deprenyl: Protective vs. Symptomatic Effect

The symptomatic treatment of moderate or advanced Parkinson's disease with the use of deprenyl as adjunct therapy in combination with levodopa has been clearly established over the past fifteen years. The first report was that of Birkmayer in 1975 followed by Lees and reports from a number of other authors. Clinical observations have concluded that deprenyl combined with levodopa does have a moderate beneficial effect in relieving wearing off or end of dose fluctuations and morning akinesia in fifty percent of subjects. This beneficial effect may continue for a year or longer in one-half of the subjects and may allow for a reduction of levodopa of twenty to thirty percent. This is essentially supported by our own observations on eighty-six patients treated with deprenyl. A controlled cooperative study by Golbe et al with ninetysix subjects indicated that deprenyl was of moderate benefit in improving the symptom fluctuations in fifty-eight percent of subjects. Golbe subsequently observed that the improvement disappeared in most of his subjects within eight months, although in others improvement continued. A recent report by Elizan et al with two hundred chronic Parkinson patients treated with levodopa and with added deprenyl indicated improvement of end of dose response in one-third to one-half of the subjects. The improvement was not maintained in the majority. In addition these authors concluded that there is no evidence that deprenyl with levodopa decreased the excess mortality of Parkinson's disease contrary to Birkmayer et al retrospective study that suggested increased life expectancy. The ratio of observed to expected deaths was 1.6 as compared to 1.46 on levodopa alone. The use of deprenyl did not appear to prevent progression of Parkinson's disease. The pharmacological mechanisms of deprenyl in Parkinson's disease are somewhat complex. Primarily deprenyl could exert an effect on symptoms by increasing the availability of nigrostriatal dopamine by preventing oxidation of dopamine through the inhibition of monoamine oxidase-B (MAO-B). In addition there may be inhibition of the re-uptake of dopamine and increased synthesis of dopamine. Deprenyl is also known to have an amphetamine like effect as well as an antidepressant effect and anticholinergic effect. With this acknowledged response one would therefore anticipate some degree of symptomatic improvement in early Parkinson's disease with either deprenyl monotherapy or deprenyl in combination with levodopa.