The pharmacology of (-)deprenyl

(-)Deprenyl (Selegilinum hydrochloricum, Jumex, Eldepryl) developed in the early sixties as a new spectrum, potent, irreversible MAO blocker (Knoll et al., 1965) was introduced as the first selective inhibitor of B-type MAO (Knoll and Magyar, 1972). In striking contrast to MAO inhibitors which strongly potentiate the pressor effect of tyramine, (-)deprenyl was described to inhibit the tyramine-induced release of noradrenaline in vascular smooth muscle (Knoll et al., 1968). The peculiar pharmacological spectrum of (-)deprenyl allowed its use as an adjuvant to the levodopa therapy of Parkinson's disease (for review see Birkmayer and Riederer, 1985). Levodopa therapy revolutionized the medication of Parkinson's disease, but severe side-effects forced the search for adjuvants with a levodopa-sparing effect. Peripheral decarboxylase inhibitors are now efficiently used for this purpose. It was reasonable to expect further potentiation and prolongation of the effect of levodopa in parkinsonians with concurrent administration of MAO inhibitors. A number of irreversible inhibitors of this type were tested in combination with levodopa, and potentiation of the antiakinetic effect of the latter was demonstrated; however, the supervention of distressing side-effect (greatly increased involuntary movements, hypertensive reactions, toxic delirium) terminated any further work along this line. There was a concensus that to give MAO inhibitors concurrently with levodopa was contra-indicated. This conclusion was called in question, however, by the development of deprenyl. (-)Deprenyl is a safe MAO inhibitor which can be given concurrently with levodopa and a peripheral decarboxylase inhibitor for the long run without the supervention of any distressing side-effects. For details regarding the pharmacology of (-)deprenyl we refer a number of reviews (Knoll 1976, 1978, 1980, 1982, 1983, 1986). The aim of this paper is to give a brief survey of the most important experimental data which demonstrate that (-)deprenyl facilitates dopaminergic tone in the brain in a peculiar manner and gives a satisfactory explanation for the observation that long-term (-)deprenyl treatment prolongs the life span of parkinsonian patients significantly (Birkmayer et al., 1985).