Other Medications:

Monoamine Oxidase B (MAO-B) Inhibitors

Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was commonly used in early-onset disease and in combination with levodopa for maintenance. Concerns over significant side effects have been raised, however.

A newer MAO-B inhibitor, rasagiline (Azilect), is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.

Side Effects. MAO-B inhibitors may have severe side effects:

• One of the most important side effects is orthostatic hypotension, particularly in people taking Sinemet plus selegiline. This condition is a sudden drop in blood pressure that causes dizziness and lightheadedness when a patient stands up. Orthostatic hypotension can also occur with other Parkinson's drugs.
• Can cause high blood pressure (hypertension) if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant. Patients suffering from depression and taking selegiline should discuss all treatment options with their doctor.
• Can also cause a dangerous increase in blood pressure if patients eat foods rich in the amino acid tyramine. While taking selegiline or rasagiline and for 2 weeks after stopping medication, patients should avoid foods such as aged cheeses, processed lunch meats, pickled herring, yeast extract, aged red wines, draft beers, sauerkraut, and soy sauce.

Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some doctors believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.

Dopamine Agonists

Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.

Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.

Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia (difficulty controlling muscle movements) can also occur with dopamine agonists. There is debate about the value of dopamine agonists as initial therapy for Parkinsonâ ' s disease. Recent research suggests that early treatment with dopamine agonists may not provide any long-term advantages compared with starting treatment with L-dopa.

Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:

• Gastrointestinal side effects (nausea and constipation). Nausea can be controlled by drugs, such as domperidone.
• Headache
• Orthostatic hypotension (sudden drop in blood pressure upon standing up)
• Nasal congestion
• Nightmares, hallucinations, and psychosis (more severe than with L-dopa for both drugs)
• Sudden sleep attacks. These can be very serious, particularly if patients are driving.

Other Dopamine Agonists.

• Specific dopamine agonists that contain ergot alkaloids include bromocriptine (Parodel), pergolide (Permax), cabergoline (Dostinex), and lisuride (Dopergin). Bromocriptine is the only ergot dopamine agonist approved for Parkinson's treatment in the United States. Pergolide and cabergoline have been found to be associated with heart valve damage and are not used in the U.S.
• Apomorphine is a dopamine agonist used as a "rescue" drug in people having on-off effects severe enough to require going off L-dopa for a few days. It is FDA-approved for treating off-time episodes of Parkinson's disease. Apomorphine is given by injection. Because it causes severe nausea and vomiting, it must be taken with an anti-nausea drug.

Catechol-O-Methyl Transferase (COMT) Inhibitors

Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Side Effects. Side effects include:

• Involuntary muscle movements
• Mental confusion and hallucinations
• Cramps, nausea, and vomiting
• Insomnia
• Headache
• Urine discoloration (a harmless side effect but should be reported to the doctor)
• Diarrhea
• Less commonly, constipation, susceptibility to respiratory infection, sweating, dry mouth

Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Anticholinergic Drugs

Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only to control tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.

Side Effects. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.

Amantadine

Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.

Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome.