Dopamine agonists for Parkinson's disease

Examples

How It Works

Dopamine agonists directly stimulate the receptors in nerves in the brain that normally would be stimulated by dopamine. Unlike levodopa, a dopamine agonist is not changed (converted) into dopamine when it enters the body, but it behaves like dopamine.

Why It Is Used

Dopamine agonists may be used in the early stages of Parkinson's disease to reduce symptoms. This approach is often effective in people who have been newly diagnosed with the disease (especially those younger than 60) because it can delay the need for levodopa and thus postpone the motor fluctuations that may occur with long-term levodopa therapy.

A dopamine agonist may be added to treatment with levodopa in the later stages of Parkinson's disease when:

• Levodopa no longer is able to adequately control symptoms on its own, and increasing the dose to provide adequate control of symptoms would cause excessive side effects.
• The person who is taking levodopa is experiencing severe motor fluctuations.

Apomorphine is an injectable, rapid-acting dopamine agonist. It is injected into the skin during occasional episodes of immobility when muscles become "stuck" or "frozen," and you are unable to rise from a chair or perform daily activities. Treatment with apomorphine is referred to as "rescue" therapy because it is used during periods when levodopa or other dopamine agonists are not effective or have worn off.

How Well It Works

When used alone in early Parkinson's disease, dopamine agonists may reduce symptoms of the disease, especially those that affect motor function, such as stiffness and slowness. Although they are not as effective as levodopa in controlling symptoms, they have the benefit of postponing the need for levodopa therapy, which in turn may help delay the onset of levodopa-related motor fluctuations.¹

When taken in combination with levodopa, dopamine agonists may:²

• Reduce the amount of levodopa needed to control symptoms, thereby reducing some side effects of levodopa.
• Improve motor function during both 'on' and 'off' periods.
• Reduce involuntary movements (dyskinesias) associated with long-term levodopa therapy, if the dose of levodopa can be reduced. However, if you have been taking levodopa for a long period (many years), dopamine agonists may also cause abnormal muscle movements.
• Prolong the effect of levodopa and reduce motor fluctuations that occur as a result of the wearing-off effect of levodopa, when the effects of a dose do not last as long as they once did.

Because apomorphine is rapid-acting, it is usually effective within 10 minutes from the time of injection. Its effectiveness lasts approximately 60 to 90 minutes.

Side Effects

The most common side effects of dopamine agonists include:

• Nausea and vomiting.
• Dizziness or fainting.
• Sudden, unpredictable "attacks" of sleepiness. These can be very dangerous if they occur while you are driving.
• Low blood pressure when you stand up (orthostatic hypotension).
• Confusion or hallucinations (seeing or hearing things that aren't really there).
• Depression.
• Inability to fall or stay asleep (insomnia).
• Jerky involuntary movements (dyskinesias). These may fade once the levodopa dosage is reduced.
• Irregular heart rate and chest pain.

Apomorphine causes severe nausea and vomiting and must be taken with anti-nausea medicine. In addition to the side effects listed above, apomorphine may also cause:

• Skin reactions at the injection site and the development of nodules beneath the skin.
• Yawning as the medicine starts to take effect.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

When dopamine agonists are used alone, they are less effective than levodopa at controlling symptoms and the dose often needs to be increased slowly over time. These medicines can cause side effects, especially sleepiness and hallucinations. Dopamine agonists tend to cause more side effects than levodopa does.

Some doctors are using dopamine agonists as initial therapy in people with newly diagnosed Parkinson's disease in order to delay treatment with levodopa. The American Academy of Neurology now recommends this approach for most people with the disease. In theory, the purpose behind delaying treatment with levodopa, especially in younger people with Parkinson's, is to delay the motor fluctuations that eventually occur with levodopa therapy. But in the long term, the same amount of people have motor fluctuations no matter what medicine is used first.³ If a dopamine agonist is used as initial therapy, levodopa may be added when the dopamine agonist is no longer able to control symptoms adequately on its own.

Pramipexole (Mirapex) and ropinirole (Requip) are the newest dopamine agonists and may cause fewer side effects than the older dopamine agonists (such as bromocriptine). These newer medicines are also more expensive.

In March 2007, the U.S. Food and Drug Administration (FDA) announced that the makers of the dopamine agonist pergolide (Permax) agreed to stop selling it because of serious side effects. Pergolide (Permax) is no longer sold because it may damage your heart valves. But stopping pergolide too quickly can be dangerous, so if you are taking this medicine, don't try to stop on your own. It's important to talk to your doctor first. There are other medicines that work like pergolide and can treat Parkinson's disease.

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.

References

Citations

1. Clarke CE, Guttman M (2002). Dopamine agonist monotherapy in Parkinson's disease. Lancet, 360(9347): 1767-1769.

2. Clarke CE, Moore AP (2007). Parkinson's disease, search date November 2006. Online version of BMJ Clinical Evidence. Also available online: http://www.clinicalevidence.com.

3. Katzenschlager R, et al. (2008). Fourteen-year final report of the randomized PDRG-UK trial comparing three initial treatments in PD. Neurology, 71(7): 474-480.

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