A selective monoamine oxidase-B inhibitor (MAOI-B) medication prescribed for people with Parkinson’s disease to extend the activity and presence of dopamine in the brain. Selegiline is called selective because it specifically blocks the action of monoamine oxidase-B, an enzyme that participates in metabolism of the monoamine neurotransmitters acetylcholine
and dopamine. Other monoamine oxidase inhibitors (MAOIs), taken primarily as antidepressants, nonselectively block metabolism of the other monoamine neurotransmitters epinephrine, norepinephrine, and serotonin as well; this action produces their antidepressant effects but also their potentially serious side effects. Nonse-lective MAOIs can allow dangerously high levels of epinephrine and the amino acid tyramine to accumulate, causing jumps in blood pressure and irregularities in heart rhythm.
Selegiline, as the then-new brand name drug Deprenyl, drew attention within the Parkinson’s community in the 1980s when doctors noticed that it seemed to improve the symptoms of Parkinson’s disease without creating many of the adverse effects (such as extensive food interactions and the risk of dangerous spikes in blood pressure) typical of nonselective MAOIs. A major study conducted from 1987 to 1992 called the DATATOP (Deprenyl and Tocopherol Antioxidative Therapy for Parkinson’s Disease) study showed that selegiline could postpone the need for levodopa therapy in de novo Parkinson’s disease (disease in people who had not yet received treatment) for up to three years, raising interest in its potential for neuropro-tective therapy. However, clinical use in the more than a decade since the study ended has not borne out this idea conclusively, and neurologists remain divided on the existence of selegiline’s neuropro-tective effects. The current consensus is that selegiline is of mild benefit in reducing the symptoms of Parkinson’s, but it does not have any clear evidence of a neuroprotective effect.
Although selegiline is effective as monotherapy for some people who have early Parkinson’s, the drug does not appear to delay the disease’s progression. Rather, it seems to have a mild to moderate dopamine agonist action, binding with dopamine receptors in brain neurons. This action, combined with its capacity to inhibit monoamine oxidase-B and delay metabolism of dopamine, allows selegiline to relieve Parkinson’s motor symptoms while dopamine depletion in the brain is still mild. In later stages of Parkinson’s, selegiline sometimes is effective as one of the adjunct therapies used to boost the effectiveness of levodopa.
The list of medications that potentially interact with selegiline, as with other MAOIs, is extensive. It includes any other antidepressant medications such as tricyclics (amitriptyline, imipramine), SSRIs (fluoxetine, paroxetine), and other MAOIs (phenelzine, isocarboxazid, tranylcypromine). Mild to moderate side effects are common: nausea, constipation, dry mouth (anticholinergic effects), dizziness, headache, vivid dreams, and hallucinations, among many others.
Because of its action on both acetylcholine and dopamine, selegiline occasionally worsens, rather than improves, the motor symptoms of Parkinson’s, especially tremors and bradykinEsia (slowed muscle response and movement). It also can cause dystonia (extreme rigidity). In a person who has Parkinson’s, determining whether these symptoms are side effects of the selegiline or indicate progression of the disease can be difficult, particularly as side effects of selegiline do not always occur immediately. Because selegiline has negligible action on norepinephrine, epinephrine, and tyrosine, there are no restrictions on medications containing tyrosine when taking selegiline as there are when taking nonselective MAOIs.
There have been serious and some fatal interactions between selegiline and the narcotic pain relief medication meperidine (Demerol), and both drugs carry warnings not to use them at the same time. Doctors commonly administer meperidine by injection for moderate to severe pain after surgery or serious injuries such as fractures. The greatest risk for unintentionally combining selegiline and meperidine occurs during emergency treatment for injuries. The person who has Parkinson’s should carry a list of the medications he or she is currently taking, as many anti-parkinson’s medications interact with other drugs as well.
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