What Conditions Are Treated with Dopamine Agonists?

Loss of dopamine production within the brain and nervous system results 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. At the same time, dopamine agonists have risks and side effects associated with prolonged use or high doses. Dopamine agonists can be a useful treatment that enhances the quality of life, but they require careful administration and monitoring of symptoms to ensure safe use.

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What Is Dopamine?

Most people know dopamine as a chemical in the brain that makes you feel happy. While the neurotransmitter dopamine does interact with dopamine receptors in the brain to produce the experience of pleasure and stimulate reward-based learning, dopamine is also used for coordinating body movements. It is further involved in the function of the kidneys, heart, and blood vessels, and is associated with hormonal changes during pregnancy.

When dopamine is not available to a part of the body with important dopamine receptor-related function, such as the brain or nerves, it causes medical conditions including Parkinson’s disease (PD), restless leg syndrome (RLS), hypertension, and hyperprolactinemia. 

Pharmacology: How the Dopamine Agonists Work 

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

Dopamine agonists are a class of drugs that is able to interact with these dopamine receptors, even when the neurotransmitter dopamine is not present. Some dopamine agonists only target one receptor (i.e., fenoldopam), but most are selective dopamine agonists, like pramipexole, and target a category of similarly functioning receptors. The ergoline dopamine agonists, on the other hand, are unselective (sometimes referred to as “dirty drugs” due to their broad actions) and can 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 the right dopamine receptors and therefore generally have fewer negative side effects. This often makes non-ergoline agonists a preferred treatment option. Non-ergoline agonists are particularly important for minimizing health risks when treating diseases in elderly people or people with pre-existing health risks.

Another class of medication that affects dopamine in the body is the indirect dopamine antagonists. Indirect agonists are drugs that don’t directly bind with dopamine receptors, but do increase how likely dopamine is to be reused by a receptor (reuptake inhibitors) or how much dopamine is released by dopamine-producing cells (releasing agents). Indirect antagonists are generally used for management of psychobehavioral conditions like ADHD, addiction, depression, and narcolepsy. Some indirect antagonists are contraindicated with monoamine oxidase inhibitors (MAOIs), a kind of medication often used to treat Parkinson’s disease.

Conditions Treated

Parkinson’s Disease

Parkinson’s disease is caused by low dopamine levels. Dopamine generation is halted by cell death in the basal ganglia. Dopamine production in the brain is sensitive to insults and can be damaged by stroke (cerebrovascular disease), encephalitis (infection of the brain), and concussions. Symptoms similar to Parkinson’s disease can be produced by some antipsychotic drugs (notably chlorpromazine and haloperidol) 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 psychological symptoms may include cognitive decline, sometimes evolving as progressive dementia, and depression.

Parkinson’s disease symptoms are often treated with levodopa (L-DOPA), monoamine oxidase type B (MAO-B), and dopamine agonist medications. 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 that is diagnosed at an early stage and in younger people. In later, more chronic stages of PD, combinations of L-DOPA, dopamine agonists, and other drugs may be used.

Restless Legs Syndrome

Restless legs syndrome (RLS) is caused by low dopamine and 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 intense uncomfortable feeling, often affecting the legs associated with an urge to move that may be typically evident in the evening when reclining or lying down. This feeling is characteristically relieved by movement, massage of the affected area, or walking around. Other body parts may become involved. It may also occur earlier in the day, especially in confined circumstances such as a long airplane flight, a meeting, or even a movie or show. This may interfere with the affected person’s ability to sleep, and may be associated with a decline in overall health.

Restless legs syndrome can be treated with levodopa, alpha-2-delta ligands, 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, and more commonly levodopa, use can result in augmentation, a situation in which continued use of the medication actually worsens symptoms. The symptoms may occur earlier, affect other parts of the body, and be more intense. Preference for prescribing one medication over another is based on individual needs and the intensity of their restless legs syndrome symptoms.

Hyperprolactinemia

Hyperprolactinemia is an excess of prolactin production in men and women which is commonly caused by a malfunction of the pituitary gland (usually due to a tumor called a prolactinoma). Prolactin is a hormone normally produced during pregnancy to decrease other sex hormones. 

In women, excessive prolactin can cause abnormal menstrual cycles, infertility, low bone mass, and, rarely, unusual discharge from the nipples (a condition called galactorrhea). 

In men, the presence of excessive prolactin can cause low libido, impotence, infertility, erectile dysfunction, low sperm count, enlargement of the breast, and, rarely, unusual discharge from the nipples. 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).

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. 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. Another common treatment is sodium nitroprusside.

Specific Medications

Non-ergoline Dopamine Agonists

These medications are those in use, along with noting their side effects:

Pramipexole (Mirapex): This pill is taken orally to treat early stages of Parkinson’s disease, and 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).

Ropinirole (Requip): This pill is taken orally to treat early and late stage Parkinson’s disease, and in late 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, involuntary muscle movements (a condition called dyskinesia), hallucinations, or a rapid drop in blood pressure (known as orthostatic hypotension).

Rotigotine patch (Neupro): 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, allowing people with gastrointestinal problems to benefit from it. Likewise, people who have trouble following a consistent daily regimen in remembering to take their medications may use the rotigotine patch to avoid missing a dose. Common side effects are involuntary muscle movements (dyskinesia), nausea, drowsiness, and dizziness.

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. 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. These receptors benefit kidney function. 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-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. These are their uses and side effects:

Bromocriptine is associated with a dose-dependent risk of heart valve fibrosis and regurgitation, when a stiff heart valve stays open and allows backflow of blood. 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.

An even higher dose-dependant risk of valvular regurgitation is associated with cabergoline. 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 undergo regular echocardiography to monitor for side effects that may put stress on the heart. As needed, the treatment regimen may need to be adjusted. 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.

Due to dopamine’s role in cognition and the brain’s reward system, 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 concern about side effects with the prescribing healthcare provider. It is recommended that these medications not be stopped suddenly without consulting with the prescriber first.

Augmentation

As noted above, some people taking dopamine agonists may begin to experience worsened symptoms while taking the medication. This phenomenon is called augmentation. The exact mechanism which causes augmentation is not fully understood, but it occurs commonly in response to dopamine agonists and related medications like L-DOPA. When dopamine agonists are used for a long period, or at higher doses, the risk of experiencing augmentation increases. Using multiple treatments in combination with varies use, 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. 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 in addition to appropriate mineral supplementation, especially iron replacement when the serum ferritin level is less than 70, are recommended. If it 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 the common neurological diseases of Parkinson’s disease and restless legs syndrome. The relief provided may have significant impacts on quality of life. If side effects occur, reach out to your prescribing health care provider. It is possible that modification of the regimen may be necessary. 

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