What Conditions Are Treated with Dopamine Agonists?

Diminished dopamine production or function within the brain and nervous system is a core problem in several diseases, including Parkinson’s disease and restless leg syndrome. Medications called dopamine agonists are able to promote dopamine effects in the body and relieve symptoms. These medications have risks and side effects, especially with prolonged use or in high doses. Dopamine agonists can be a useful treatment that enhances the quality of life, but they require careful administration and monitoring for safety.

What Is Dopamine?

The neurotransmitter dopamine is involved in the function of the kidneys, heart, and blood vessels, and is associated with hormonal changes during pregnancy. It also interacts with dopamine receptors in the brain to produce the experience of pleasure, which stimulates reward-based learning and behavior. Dopamine action in the brain also coordinates body movements.

When there is a lack of dopamine, dopamine receptors, or dopamine activity in any area of the body, symptoms develop. Some medical conditions associated with low dopamine activity include Parkinson’s disease (PD), restless leg syndrome (RLS), hypertension, and hyperprolactinemia. 

Pharmacology: How the Dopamine Agonists Work 

Dopamine agonists are a class of drugs that interact with dopamine receptors, even when dopamine is not present.

There are five types of dopamine receptors that belong to two categories:

• D1-like: D1 and D5 
• D2-like: D2, D3, and D4 

When dopamine binds with a D1-like dopamine receptor, the active receptor increases communication between neurons, while an active D2-like dopamine receptor decreases neuron communication. Cells that use dopamine receptors for signaling may have one or more types of receptors. 

Some dopamine agonists only target one receptor (i.e., fenoldopam). Most are selective dopamine agonists, like pramipexole, and target a category of similarly functioning receptors.

The ergoline dopamine agonists are unselective and have broad actions. This makes them more likely to cause unintended consequences in body systems unrelated to the disease being treated.

Classes of Dopamine Agonist Medications

Dopamine agonist medications come in two drug classes—ergoline and non-ergoline. 

• Ergoline agonists are derived from ergot fungus and have more unwanted interactions with non-target receptors in the body than the more recently developed class of dopamine agonists, non-ergoline agonists. 
• Non-ergoline agonists are more precise in targeting specific dopamine receptors and therefore generally have fewer side effects. This often makes non-ergoline agonists a preferred treatment option. Non-ergoline agonists are particularly important for minimizing side effects for people with pre-existing health risks.

Another class of medication that affects dopamine in the body is indirect dopamine agonists. Indirect agonists are drugs that don’t directly bind with dopamine receptors.

Their actions include:

• Reuptake inhibitors: Increase how likely dopamine is to be reused by a receptor
• Releasing agents: Increase how much dopamine is released by dopamine-producing cells

Indirect antagonists are generally used for the management of psychobehavioral conditions like ADHD, addiction, depression, and narcolepsy. Some indirect antagonists are contraindicated with monoamine oxidase inhibitors (MAOIs), which are usually used as antidepressants, and are also sometimes prescribed for people who have Parkinson’s disease.

Conditions Treated

Parkinson’s Disease

Parkinson’s disease is caused by low dopamine levels that occurs when dopamine production is slowed due to cell death in the basal ganglia. Symptoms similar to Parkinson’s disease can be produced by some antipsychotic drugs (notably haloperidol and risperidone) and by neurotoxic synthetic chemicals (such as MPTP).

The physical symptoms of Parkinson’s disease include: 

• Muscle rigidity
• Tremor of resting limbs
• Delayed or slowed voluntary movements
• Difficulty balancing and falls

The non-motor symptoms may include cognitive decline, sometimes evolving as progressive dementia, and depression.

Treatment

Parkinson’s disease symptoms are often treated with levodopa (L-DOPA), monoamine oxidase type B (MAO-B) inhibitors, and dopamine agonist medications. L-DOPA converts to dopamine, and MAO-B inhibitors prolong the action of available dopamine. These prescription drugs restore activity to dopamine receptors in areas of the brain that have lost functional dopamine-producing cells.

Dopamine agonists can be used as a first-line treatment for symptoms of Parkinson’s disease at an early stage and in younger people. In later stages of the disease, combinations of L-DOPA, dopamine agonists, and other drugs may be used.

Restless Legs Syndrome

Restless legs syndrome (RLS) is associated with low dopamine levels and low iron levels in the corpus striatum, a part of the basal ganglion that participates in learning and motor function.

The symptoms of RLS include an intensely uncomfortable feeling, often affecting the legs, and associated with an urge to move. It is more common during the evening when reclining or lying down. This feeling is usually relieved by movement, massage of the affected area, or walking around. The condition often interferes with sleep and may be associated with a decline in overall health.

Other areas of the body may become involved and the symptoms can also occur earlier in the day, especially in confined circumstances such as a long airplane flight or a meeting.

Treatment

Restless legs syndrome can be treated with levodopa, alpha-2-delta ligands (for example gabapentin), dopamine agonists, or mineral supplements such as iron or magnesium. Opiates such as long-acting agents like methadone are sometimes prescribed at low doses in extreme or intractable cases of restless legs syndrome.

Dopamine agonists at higher doses may lead to some side effects that may make alpha-2-delta ligands preferable. Dopamine agonist or levodopa can result in augmentation, a situation in which continued use of the medication actually worsens symptoms. With augmentation, the symptoms may occur earlier, affect other parts of the body, and be more intense.

Hyperprolactinemia

Hyperprolactinemia is an excess of prolactin production. It can affect males or females and it is caused by a malfunction of the pituitary gland (usually due to a tumor called a prolactinoma). Prolactin is a hormone normally produced during pregnancy. 

The presence of a large prolactinoma can cause headaches, disruptions in the field of vision, and weakening of the eye muscles (known as external ophthalmoplegia).

Other symptoms differ for males and females:

• Females: Excessive prolactin can cause abnormal menstrual cycles, infertility, low bone mass, and, rarely, unusual discharge from the nipples (a condition called galactorrhea). 
• Males: The presence of excessive prolactin can cause low libido, impotence, infertility, erectile dysfunction, low sperm count, enlargement of the breasts, and, rarely, unusual discharge from the nipples.

Treatment

The production of prolactin is usually triggered by an absence of dopamine, so low doses of dopamine agonists like cabergoline and bromocriptine can be used to suppress prolactin production.

Treatments for hyperprolactinemia that is unresponsive to dopamine agonists may include combinations of medications and transsphenoidal surgery.

Hypertension

Hypertension is high blood pressure. The kidneys are especially important for regulating blood volume and pressure. There are many different treatments used for high blood pressure, and dopamine is not usually part of the treatment regimen.

Due to dopamine’s role in kidney function, emergency situations involving extremely high blood pressures can be temporarily treated by doses of the dopamine agonist called fenoldopam.

Specific Medications

Non-ergoline Dopamine Agonists

Mirapex (pramipexole): This pill is taken orally to treat early or later stages of Parkinson’s disease. In late stages, it may be combined with L-DOPA. Pramipexole is preferred for treating Parkinson’s disease with increasing psychiatric effects, especially when associated with depression or bipolar disorder. It is also used to treat restless legs syndrome (RLS).

It is metabolized by the kidneys and should not be taken by people with poorly functioning kidneys. Common side effects include drowsiness, sudden sleep attacks, nausea, and swelling in the limbs. People taking pramipexole may also experience hallucinations, compulsive eating, and impulse control disorder (which may manifest with uncontrolled gambling, online shopping, or other behaviors).

Requip (ropinirole): This pill is taken orally to treat early and late-stage Parkinson’s disease, and in later stages of Parkinson’s disease may be combined with L-DOPA. It is also used to treat restless legs syndrome (RLS).

Dose adjustments may need to be made for people who have severe liver function impairment. Possible side effects include impulse control disorder, upset stomach, constipation, sleepiness, dyskinesia (a movement disorder that causes involuntary muscle movements), hallucinations, orthostatic hypotension (a rapid drop in blood pressure upon standing), and impulse control problems.

Neupro (rotigotine patch): This adhesive patch is used to treat early and late Parkinson’s disease and restless legs syndrome (RLS). It is applied to the skin, which reduces some of the potential side effects. People who have gastrointestinal problems or who have trouble following a consistent daily regimen or remembering to take their medications may benefit from using a patch instead of taking a pill.

Common side effects are dyskinesia, nausea, drowsiness, dizziness, and impulse control problems.

Apomorphine: This injection can be given under the skin when Parkinson’s disease suddenly becomes resistant to other dopamine agonists. Side effects include hypotension (low blood pressure), headaches, dizziness, difficulty standing up, psychological problems, or an adverse reaction at the injection site.

Piribedil: This pill is taken orally to treat early Parkinson’s disease, and in later stages, it may be combined with L-DOPA. This medication is mainly used in Europe. Piribedil may also benefit memory in aging people, but is used with caution as it can also have negative psychological effects, like impulse control disorders and sleep attacks (sudden loss of consciousness).

Fenoldopam: This short-acting injection selectively targets D1 receptors. Blood vessels respond to fenoldopam by relaxing (vasodilating), so it is used to lower blood pressure when blood pressure is extremely high (such as in a hypertensive emergency). Fenoldopam has also been considered for treatment for people with hypertension that's related to kidney disease and renal failure.

Ergoline Dopamine Agonists

Bromocriptine, dihydroergocryptine, and cabergoline are pills taken orally that can be used alone or in combination to treat Parkinson’s disease. These drugs are also helpful in treating hyperprolactinemia.

Bromocriptine is associated with a dose-dependent risk of heart valve fibrosis and regurgitation. This condition causes the heart valves to stiffen and to stay open, allowing backflow of blood. This medication is rarely used due to side effects. Taking more than 30 milligrams (mg) of bromocriptine per day is not recommended. Bromocriptine’s other side effects include hypotension, nausea, headache, vomiting, confusion, and hallucinations.

Cabergoline has an even higher dose-dependant risk of valvular regurgitation. Doses of cabergoline greater than 3 mg per day are not recommended. Cabergoline’s additional side effects include nausea, vomiting, sleepiness, dizziness, hypotension, and swelling of the limbs.

Risks and Side Effects

Risks

People taking ergoline dopamine agonists should be regularly monitored for cardiac (heart) side effects, such as with echocardiography.

Ergoline dopamine agonists should not be prescribed to people who have a history of hypertension or fibrosis affecting the lungs, heart, heart valves, or abdomen. Ergoline dopamine agonists also increase the risk of liver cancer and can interfere with how other drugs are metabolized, particularly drugs taken to treat kidney or liver failure.

High doses of dopamine agonists can lead to impulse control disorders. Impulse control disorders can cause outbursts, antisocial actions, and addictive behaviors.

Generally, side effects associated with dopamine agonists include:

• Fibrosis of the heart or lungs
• Cardiac valve regurgitation 
• Heart failure
• Constipation
• Sweating
• Nausea
• Dizziness
• Fatigue
• Tachycardia (rapid heart rate)
• Headaches
• Peripheral edema (swelling in limbs)
• Daytime sleepiness
• Sleep attacks (sudden loss of consciousness)
• Sleep-disordered breathing
• Withdrawal
• Hallucinations
• Somnolence
• Impulse control disorders
• Psychosis

Discuss any concerns about side effects with your prescribing healthcare provider. These medications should not be stopped suddenly without consulting with the prescriber first.

Augmentation

Some people taking dopamine agonists may begin to experience worsened symptoms while taking the medication. This phenomenon is called augmentation.

Augmentation occurs commonly with dopamine agonists and related medications like L-DOPA. When dopamine agonists are used for a long period, or at higher doses, the risk of augmentation increases.

Using multiple treatments in combination, rather than depending solely on one primary treatment is often a precaution taken to avoid augmentation or loss of effectiveness of any one type of dopaminergic drug.

Studies of augmentation by dopamine agonists in restless legs syndrome treatment have found some risks with each treatment option.

For example:

• In people using immediate-release ropinirole over 66 weeks, augmentation occurred in 4% of study participants.
• In people using immediate-release pramipexole over 26 weeks, augmentation occurred in 9.2% of participants.
• Another long-term study of pramipexole found augmentation in 42% of users.
• In people using rotigotine patches, 13% of users experienced augmentation over a 5-year period. 

To avoid augmentation with long-term treatment, lower doses of dopamine agonists and iron replacement (when the serum ferritin level is less than 70) are recommended. If augmentation occurs, the medication may need to be discontinued, but it may be successfully reintroduced later.

A Word From Verywell

Dopamine agonists have an important role in the treatment of several common neurological diseases. The medication may significantly improve quality of life. If side effects occur, reach out to your prescribing healthcare provider—modification of your treatment regimen may be necessary.