Neuropharmacology & Neurotherapeutics
Oct. 23, 2023
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Selegiline hydrochloride, a levorotatory acetylenic derivative of phenethylamine, is a potent monoamine oxidase inhibitor that was developed as a "psychic energizer" in Hungary in 1964 (08). Later studies showed that it inhibited monoamine oxidase type B rather selectively (21). Monoamine oxidase inhibitors were considered potentially useful in the treatment of Parkinson disease, as blocking its breakdown could enhance dopamine transmission. However, nonselective monoamine oxidase inhibitors did not prove beneficial when given as monotherapy, and hypertensive crises were a problem. It was then discovered that selegiline, as a selective monoamine oxidase type B inhibitor, could be combined with levodopa without the "cheese effect" (hypertensive crisis developing when monoamine oxidase inhibitors are combined with foods, such as cheese, containing the amino acid tyramine). In 1975 clinical studies demonstrated that selegiline combined with levodopa and a peripheral dopa decarboxylase inhibitor had an antiparkinsonian effect and that fluctuations were reduced (02). Selegiline, commonly referred to in the clinical and pharmacological literature as L-deprenyl, was approved in the United Kingdom in 1982 and by the United States Food and Drug Administration in 1989 as a combination therapy with levodopa. It is sold under various brand names around the world.
Selegiline has become the most controversial drug in the treatment of Parkinson disease during the past decade. In 1995 a United Kingdom study reported a higher mortality in patients treated with a selegiline and levodopa combination. Despite this controversy, selegiline continues to be prescribed by neurologists in the United States because the drug has a low side-effect profile and improves the quality of life.
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