Parkinsons disease is a degenerative condition of the neurologic system that has received considerable attention as of late due to high profile celebrities being stricken with the disease, among them Muhammad Ali and Michael J. Fox. It is associated with aging, and the key pathologic finding is the destruction of neurons in the substantia nigra area of the brain that are responsible for dopamine production; the resulting low dopamine levels are responsible for symptom production.
Levodopa
This is a precursor to dopamine and is converted to dopamine in the brain by an enzyme known as tyrosine hydroxylase. Less than 1 percent of the ingested levodopa is converted to dopamine in the brain, which is why sometimes an adjunctive drug such as carbidopa is added. It functions to inhibit the enzyme known as dopa-decarboxylase, which tends to convert levodopa to dopamine before it enters the brain. Patients on levodopa and carbidopa have better symptom control than patients on levodopa alone; however, they also have an increased incidence of side effects. Side effects may include nausea and vomiting, and occasionally cardiac rhythm disturbances.
Monoamine Oxidase B Inhibitors (MAO-B inhibitors)
These inhibit the enzyme MAO-B, which usually breaks down dopamine in the brain. The two FDA approved drugs in this class are rasagiline and selegiline. Taking one of them can result in improved available dopamine, which can help treat symptoms. Side effects include nausea and vomiting, sleep, hallucinations, and dizziness (especially upon standing). Patients on MAO-B inhibitors must also avoid certain antidepressants and avoid certain foods such as cheese or wine as advised by their clinician to avoid adverse reactions.
Dopamine Agonists
These include bromocriptine, pergolide, cabergoline, pramipexole and ropinirole. Their method of action is to directly stimulate dopamine receptors. Side effects include confusion, hallucinations, sleep disorders, dizziness (especially upon standing) and impulsive behavior (gambling, hypersexuality, etc.). Pergolide and cabergoline also have additional damaging effects on heart valves, and older agents (such as bromocriptine) can cause constriction of blood vessels and painful red discoloration of the skin and thus are not used much anymore.
Catechol-O-Methyl Transferase Inhibitors (COMT inhibitors)
These medications inhibit COMT, which is a key enzyme that breaks down levodopa before it can cross into the brain. Using these medications increases the amount of levodopa available in plasma for transfer into the brain, and two approved drugs in this class are tolcapone and entacapone. The main side effects include diarrhea, movement disorders and liver toxicity. It is noteworthy that liver toxicity is not a side effect of entacapone.
Amantadine
This is an antagonist at the NMDA receptor, which has shown effects that reduce the movement disorders present in Parkinson's disease. Interestingly, it can also be used for influenza virus treatment. Side effects include blurred vision, sleep disruption and dizziness.
References
- Neurology. "Treatments for Parkinsons Disease---past achievements and current clinical needs." Poewe W. Volume 72, Issue 7 Suppl 2 (February 2009)
- Clinics in Geriatric Medicine. "Parkinsons Disease: Background, Diagnosis, and Initial Management." Albin R. Volume 22, Issue 4 (November 2006)
- Neurologic Clinics. "Medical Treatment of Parkinson Disease." Stacy M. Volume 27, Issue 3 (August 2009)
