Dopamine precursors and agonists for restless legs syndrome

Examples

Dopamine precursors

Generic Name	Brand Name
levodopa	Sinemet

Dopamine agonists

Generic Name	Brand Name
apomorphine	Apokyn
bromocriptine mesylate	Parlodel
cabergoline	Dostinex
pramipexole	Mirapex
ropinirole hydrochloride	Requip

How It Works

Dopamine precursors are drugs that the brain converts to dopamine, a chemical (neurotransmitter) involved in controlling movement. Dopamine is involved in movement, sleep, emotions, alertness, and addictive behavior.

Dopamine agonists directly stimulate nerves in the brain that are not naturally being stimulated by dopamine.

Why It Is Used

Dopamines are generally prescribed to treat Parkinson's disease. But there seems to be a relationship between restless legs syndrome and abnormalities in how the body produces or uses dopamine. A doctor may prescribe medicine as treatment for continuous symptoms that frequently disturb sleep, in which case dopamine agonists are usually the first choice. Requip and Mirapex have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of moderate to severe restless legs syndrome.

How Well It Works

The dopamine agents that are effective and well studied in treating restless legs syndrome and involuntary or jerking leg movements (periodic limb movements) are ropinirole, pramipexole, and levodopa.¹

Studies have shown that these drugs have helped some people control or improve their symptoms and have reduced the number of sleep disturbances.² Although they may seem to help at first, in some people these medicines seem to make symptoms worse later by a process called augmentation. Because this undesired outcome is most associated with regular use of levodopa, most patients who require daily medicine will need a dopamine agonist.

Side Effects

Side effects that may occur with levodopa, a dopamine precursor, include:

• Nausea and vomiting.
• Headache, dizziness, or fainting.
• Insomnia, agitation, anxiety, malaise, fatigue, and euphoria.

The most common side effects of dopamine agonists are:

• Nausea.
• Nasal congestion.
• Fatigue.
• Fluid retention.
• Unwanted sleepiness.

These side effects can sometimes be relieved by combining dopamine with other medicines, such as domperidone or carbidopa. Certain rare side effects, called impulse control disorders (such as pathological gambling), have also occurred in a few RLS patients.

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

What To Think About

If you begin experiencing symptoms in the daytime as a result of these drugs, you may also be prescribed opioids or benzodiazepines.

More study is needed to discover the full range of side effects. But two dopamine agonists (ropinirole and pramipexole) have been reviewed by the U.S. Food and Drug Administration (FDA) and are approved specifically for treatment of moderate to severe restless legs syndrome.

Problems related to the dosing of dopamine precursors and agonists can occur, such as:

• Rebound. This occurs when symptoms become worse at the end of a dosing period, usually late at night or in the morning.³
• Augmentation, which means that symptoms generally get worse. Symptoms begin to be noticed progressively earlier in the day, often in the afternoon or evening. Augmentation is most often a side effect of long-term dopamine use and usually becomes worse with increasing dosage. People with severe augmentation experience symptoms constantly. The discomfort may intensify and spread to the torso or the arms. Discontinuing the medicine will usually return symptoms to the premedication level, even though at first they may temporarily get worse.³

To prevent rebound or augmentation, it may be helpful to split or lower the dosage or change the usual time the dose is taken.

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Author:	Kathe Gallagher, MSW Cynthia Tank	Last Updated: April 4, 2007
Medical Review:	Adam Husney, MD - Family Medicine Wayne A. Hening, MD - Neurology Karin M. Lindholm, DO - Neurology
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