(-)
Deprenyl (
Selegiline,
Jumex,
Eldepryl, Movergan), a close structural relative to phenylethylamine (PEA), is a
drug of a unique pharmacological spectrum. (a) It is highly potent and selective irreversible inhibitor of B-type
monoamine oxidase (
MAO), a predominantly glial
enzyme in the brain, the activity of which significantly increases with age. (-)
Deprenyl was the first selective inhibitor of
MAO-B described in literature, became the worldwide research tool used for blocking selectively B-type
MAO, and is still the only
MAO-B inhibitor in clinical use. (b) (-)
Deprenyl interferes with the uptake of
catecholamines and indirectly acting
sympathomimetics because it is handled by the catecholaminergic neuron similarly to the physiological substances transported through the axonal end-organ and vesicular membrane. The unique behavior of (-)
deprenyl is that, in striking contrast to PEA and its relatives, it does not push the transmitter from the storage places, i.e., it is not a releaser. The net result is that (-)
deprenyl inhibits the releasing effect of
tyramine and is presently the only safe
MAO inhibitor which can be administered without
dietary restrictions. (c) Maintenance on (-)
deprenyl enhances selectively
superoxide dismutase (SOD) and
catalase activity in the striatum. This effect is unrelated to the
MAO and uptake inhibitory effects of the
drug. (d) Maintenance on (-)
deprenyl facilitates the activity of the nigrostriatal dopaminergic neurons with remarkable selectivity. This effect is also unrelated to either the
MAO or the uptake inhibitory effects of the
drug. All in all, (-)
deprenyl maintains the activity of the nigrostriatal dopaminergic machinery on a higher activity level and slows down its age-related decline. Male rats maintained on (-)
deprenyl lost their capacity to ejaculate later, retained their learning ability longer, and lived longer than their saline-treated peers. Parkinsonians on
levodopa plus (-)
deprenyl (10 mg daily) lived significantly longer than those on
levodopa alone. (-)
Deprenyl is the first
drug which retards the progress of
Parkinson's disease. Freshly diagnosed parkinsonians maintained on (-)
deprenyl did not require
levodopa until significantly later than their placebo-treated peers. Maintenance on (-)
deprenyl significantly improved the performance of patients with
Alzheimer's disease. It is concluded that in
Parkinson's disease and
Alzheimer's disease patients need to be treated daily with 10 mg (-)
deprenyl from diagnosis until death, irrespective of other medication.(ABSTRACT TRUNCATED AT 400 WORDS)