Selegeline (Deprenyl) was demonstrated to work in Parkinsons Disease in the late 1970s. It is a selective, irreversible inhibitor of B-type monoamine oxidase (MAO), a predominantly glial cell enzyme in the brain.
This class of drugs was seen as the first potential neuroprotective drugs in the early 1990s. While animal studies and some initial human studies were consistent with this potential benefit a controversial yet important study in 1995 put to rest for a time the "oxidative stress" hypothesis which suggests that the oxidative metabolism of dopamine produces excessive free radicals that gradually kill the dopaminergic neurons, which bear the brunt of the pathology of Parkinson's disease. This hypothesis was attractive as selegiline selectively enhances superoxide dismutase (SOD) and catalase activity in the striatum and protects the nigrostriatal dopaminergic neurons from known neurotoxins such as 6-hydroxydopamine and MPTP (which caused a forn of designer drug parkinsonism in California in the 1970's). Selegiline is metabolised to L-methamphetamine and L-amphetamine which may have antidepressant properties but also appear to be potential neurotoxins. Recently selegiline has been shown to induce antioxidative proteins and more evidence on dopamine neurotoxicity has emerged so the question remains open.
The overwhelming evidence is now that selegiline is a relatively safe drug (but do note that predictable fatal drug interactions have been reported) and some await the long term trials of its designed brother rasagiline with interest.
- Lees AJ, Shaw KM, Kohout LJ, Stern GM, Elsworth JD, Sandler M, Youdim MB. Deprenyl in Parkinson's disease. Lancet. 1977 ;2(8042):791-5
- Lees AJ. Comparison of therapeutic effects and mortality data of levodopa and levodopa combined with selegiline in patients with early, mild Parkinson's disease. BMJ 1995;311:1602-1607
- Henchcliffe C, Schumacher HC, Burgut FT. Recent advances in Parkinson's disease therapy: use of monoamine oxidase inhibitors. Expert Rev Neurother. 2005;5(6):811-21