Monoamine oxidase-B inhibitors (MAOBIs), mainly selegiline hydrochloride, work by preventing the breakdown of dopamine in the body by the MAO-B enzymes, and thereby keeping the concentration of dopamine stable in the body. This prevents the dyskinesia associated with Parkinson's, because the level of dopamine in the body and the frequency of the shaking associated with disease are directly related. Therefore, even though dopamine-producing cells are being broken down, selegiline helps the surviving neurons to produce more dopamine, and so the symptoms do not worsen. Unfortunately, although MAO-B enzymes are the most efficient way for the body to break down dopamine, there are also MAO-A enzymes that can be used to break down dopamine in small quantities. This limits the effects of MAO-B inhibitors by a small amount. This problem is lessened by the fact that more than 60% of the brain's MAO enzymes are of the B type, and after age 60, MAO-B enzymes increase (Bernstein 1994). Selegiline is metabolized to a chemical similar to amphetamine, which means patients taking selegiline often show an improvement in mood and energy as well as motor function.
If selegiline is used early in treatment, before L-dopa, some evidence shows that it can delay the need for L-dopa for up to nine months (and thus prevent DID and other side effects for that long, as well) (Henkel 1998). Usually, though, selegiline is administered to patients along with L-dopa, so that they can take a lower dosage of L-dopa than is usually prescribed. If used after L-dopa has begun to wear off, this drug is moderately effective in 50%-70% of cases, allowing L-dopa dosages to be reduced by 15% (Golbe 1988). Lower dosages of L-dopa increase the amount of time that patients can use that particular drug therapy, since L-dopa loses its efficiency over time. Also, lower dosages of L-dopa mean fewer and less severe side-effects from L-dopa, which means that the common problems (such as dyskinesias, motor fluctuations, and many more) are lessened.
Much research has been done on selegiline, and it has found both positive and negative side effects. There is some possibility that the drug may also prevent dopamine-producing neurons from dying, and thereby delaying the progression of Parkinson's Disease (called "neuroprotection"). Studies in animals (Bernstein 1994) have shown that injection of dopamine in animals can actually prevent the onset of Parkinson's disease, making selegiline one of the most effective neuroprotective drugs around. Another exciting prospect of selegiline is that in some studies, selegiline has been observed to cause an increase in neural cell growth, and promotes the production of growth factors for neural cells. This could mean that selegiline might be able to help minimize the devastating neural cell loss of Parkinson's by increasing cell growth.
Unfortunately, There have been concerns about the use of selegiline: a study by the British Medical Journal found that patients with early, mild Parkinson's, who took both L-dopa and selegiline, had a much higher death rate than those who took only L-dopa (Ben-Schlomo et al 1998). The increased death toll came primarily in years four and five. The reasons for these deaths were not consistent, though the selegiline group was more likely to be hurt by falling and had a greater incidence of dementia than the L-dopa group.
One suggested mechanism was that selegiline might increase the risk of a disturbance of cardiac rhythm or compromise the cardiovascular system through orthostatic hypotension. Other possibilities are that combination treatment may have accelerated nigral cell death or that selegiline may have had an adverse drug interaction with a drug not included in the trial.(Ben-Schlomo et al 1998)
Because of these findings, and the prevalence of other drugs to supplement L-dopa, selegiline is no longer prescribed very frequently.
Although it seems that selegiline has many possibilities in terms of positive effects, there are a few problems. It does not stay effective much longer than four years in a given patient, for instance, and also the potential extra benefits as listed above (neuroprotection, etc.) have not been proven and are currently being debated as to their truth by the medical community. The most common side-effects are:
Information from:
Parkinson's Disease at Harvard