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Dopamine Precursors

Dopamine Replacement Therapy


About dopamine precursors

A dopamine precursor is a substance that can be converted into dopamine in the body. Dopamine acts a neurotransmitter that helps regulate body movements and other motor and cognitive functions. Adequate amounts of dopamine in the brain help promote smooth, coordinated movement. Inadequate levels of dopamine triggers symptoms such as tremor, rigidity and bradykinesia (slowness of movement). Dopamine itself is not typically used as a medication because when it is taken orally, it does not cross the blood-brain barrier, and thus cannot be transported into the brain.

Levodopa (also known as L-Dopa) is the most commonly used dopamine precursor. It occurs naturally in plants and animals and is converted into dopamine in the human body. Legumes such as fava beans contain high levels of levodopa. A synthetic form of levodopa is available and used as a medication.

Once in the body, levodopa is absorbed in the intestines and then enters the bloodstream, where it is transported to the brain. Most of the levodopa is immediately broken down by certain substances in the body – primarily decarboxylase enzymes but also catecholamine-O-methyltransferase (COMT). Very little of the levodopa actually makes it to the brain, where enzymes in the brain convert the levodopa into dopamine. Therefore, levodopa is usually administered with other substances that delay the breakdown of levodopa until it reaches the brain.

In the United States, levodopa is often administered along with carbidopa, which inhibits enzyme activity, allowing more levodopa to reach the brain. Lower levels of levodopa can be administered when it is combined with carbidopa. This helps alleviate common side effects associated with levodopa such as nausea and vomiting.

In some cases, levodopa and carbidopa combinations may also include entacapone, a COMT inhibitor. This substance not only helps more levodopa reach the brain, but also extends the amount of time that levodopa remains active in the brain. However, some concern has been expressed about the use of entacapone since a similar medication (tolcapone) has caused liver disease in a few adults. Levodopa therapy is sometimes used to refer to levodopa combinations.

Levodopa therapy is taken orally in pill form. It may also be available in a dissolvable tablet form for patients with difficulty swallowing. The medications are available in both regular formulations and time-release formulations that cause the drug to remain active in the system for longer periods of time. They are also available in varying strengths and ratios (e.g., amounts of levodopa and carbidopa).

Dopamine precursor formulations include:



Dopar, Larodopa

Levodopa and carbidopa

Sinemet, Parcopa

Levodopa, carbidopa and entacapone


The benefits of levodopa therapy are usually experienced soon after beginning the medication. However, the dosage may be gradually increased over time in order to be most effective and the drugs involved in levodopa therapy may need to be taken for months before their full effect is felt. Levodopa can dramatically increase the quality of life for people with movement disorders such as Parkinson’s disease.

Eventually, the effectiveness of levodopa therapy will decrease, in which case patients usually experience a gradual worsening of symptoms (called the “wearing off effect”) or periodic attacks of more severe symptoms (called the “on-off effect”). Because of this, other drugs are sometimes used with levodopa therapy, including:

  • Dopamine stimulators (also called dopamine agonists). These drugs mimic the effects of dopamine in the brain, directly stimulating dopamine receptors to increase dopamine levels in the brain. No metabolic conversion is necessary for this to occur. Dopamine stimulators are less effective than levodopa therapy, but are also less likely to involve a wearing off effect and may delay the onset of certain side effects (e.g., dyskinesias). These drugs may be used with or prior to levodopa therapy.
  • MAO-B inhibitors (e.g., selegiline [Atapryl, Eldepryl, Carbex, Selpak], rasagiline [Azilect]). These drugs inhibit the inactivation of dopamine in the brain caused by the enzyme monoamine oxidase B (MAO-B). This may extend the effectiveness of levodopa therapy or dopamine stimulators.
  • Amantadine. Originally developed as an antiviral medication, amantadine has been found to have an effect similar to dopamine. Amantadine is sometimes used to treat side effects of levodopa therapy. This medication may be used by itself or with other dopaminergic agents.
  • Anticholinergics (e.g., trihexyphenidyl [Artane, Trihexane, Trihexy], benztropine [Cogentin]). These drugs increase the effects of dopamine in the brain by reducing the effects of acetylcholine. An imbalance between the neurotransmitters dopamine and acetylcholine is associated with movement problems. Anticholinergics are used to reduce symptoms of tremors and rigidity. They may be used alone or with levodopa

In addition, a physician may recommend that patients experiencing the wearing-off or on-off effect periodically interrupt their levodopa schedule, or change dosages. Patients who experience any fluctuations in their symptoms while taking levodopa should report these changes to their physician.


Conditions treated

The dopamine precursor levodopa (also called L-Dopa) is typically used to treat symptoms of Parkinson’s disease. This medication may help reduce tremors (shaking), rigidity (muscle stiffness) and bradykinesia (slowness of movement). It may also improve gait, posture, swallowing, speech, handwriting, vigor, alertness, sense of well-being, excess salivation and seborrhea (oily, crusty, scaly skin). However, dopamine precursors do not cure Parkinson’s disease or delay its progression.

For four decades, levodopa has been the chief medication treatment for Parkinson’s disease. Seventy to 80 percent of patients with this illness are treated with levodopa, according to the Parkinson’s Disease Foundation. Roughly three-quarters of patients with Parkinson’s disease who take levodopa therapy gain some benefit from it, according to the National Institute of Neurological Disorders and Stroke (NINDS).

Levodopa has also been used in the treatment of:

  • Dopa-responsive dystonia (DRD)
  • Multiple system atrophy (MSA)
  • Restless leg syndrome (RLS)
  • Periodic limb movement disorder (PLMD)

Some evidence suggests that levodopa may also be helpful in treating children with cerebral palsy.

Conditions of concern

Patients are urged to tell their physician if they have been diagnosed with any medical condition. These include any allergies, especially if they have ever experienced an allergic reaction to previous use of the dopamine precursor levodopa (also called L-Dopa) or an allergic reaction to other substances such as foods, preservatives or dyes.

Other conditions of concern with regard to using dopamine precursors include:

  • Blood vessel disease
  • Diabetes
  • Glaucoma
  • Heart conditions or history of heart attacks
  • Hormone problems
  • Kidney or liver disease
  • Lung disease (e.g., asthma, emphysema, bronchitis)
  • Melanoma
  • Mental illness
  • Seizure disorders
  • Skin cancer
  • Stomach ulcers
Side effects

Potential side effects

Side effects are common for patients who take dopamine precursors. In most cases, side effects are relatively minor, but some can be severe.

The most common side effects of the dopamine precursor levodopa (also called L-Dopa) are nausea and vomiting. Other common side effects of levodopa include dyskinesia (uncontrollable movements), sudden sleep onset, hallucinations and psychosis. Many patients taking levodopa develop dyskinesias within the first year of treatment. These can range from mild (e.g., head bobbing) to severe (e.g., violent jerking of the limbs). Motor complications occur in about half of all patients taking levodopa after 5 to 10 years of treatment.

Additional side effects may include:

  • Abdominal pain
  • Abnormal increase in muscular activity (hyperkinesia)
  • Change in sense of taste
  • Confusion
  • Decreased attention span
  • Diarrhea
  • Difficulty sleeping
  • Discoloration of sweat, urine or saliva
  • Dizziness
  • Drowsiness
  • Dry mouth
  • Fatigue
  • Headaches
  • Increased sweating
  • Loss of appetite
  • Low blood pressure upon standing (orthostatic hypotension)
  • Memory loss
  • Nervousness
  • Nightmares
  • Speaking difficulties
  • Weakness

Patients who use levodopa for prolonged periods of time or who have to regularly increase dosage levels may be more likely to experience certain side effects (e.g., dyskinesia). Long-term users may also experience periods when the medication suddenly stops working for a period of time before suddenly starting to work again.

Many patients who take levodopa for restless leg syndrome initially experience an increase of symptoms during the morning, afternoon or early evening hours. This is known as augmentation. Patients who experience this side effect should consult a physician, who may recommend that the patient stop taking levodopa. In general, dopamine precursors appear to cause fewer side effects in patients who have restless leg syndrome than in patients who have Parkinson’s disease.

Because levodopa may cause drowsiness, people are urged to avoid taking it before certain activities (e.g., driving, using machinery) until they know how it is likely to affect them.


Drug or other interactions

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, nutritional supplements or herbal medications.

Certain medications may interfere with dopamine precursors such as levodopa (also known as L-Dopa). These include:

  • Alcohol
  • Antacids
  • Antidepressants
  • Antiseizure drugs
  • Antihypertensives
  • Dopamine blockers (e.g., antipsychotics, tranquilizers)
  • MAO inhibitors
  • Certain illegal drugs (e.g., cocaine)
  • Tranquilizers
  • Vitamin preparations with pyridoxine (vitamin B6) and other vitamins

In addition, a diet that is high in protein or vitamin B6 may prevent levodopa from being efficiently absorbed. Foods rich in vitamin B6 include beans, fish, liver, peas and whole-grain cereals. Protein can delay levodopa absorption. On the other hand, sugar may increase the speed of levodopa absorption. In general, taking levodopa on an empty stomach increases its therapeutic effect, but also increases certain side effects such as nausea. Patients are urged to discuss with their physician how to plan a proper diet while taking dopamine precursors.

How to use

Pregnancy use issues

Although formal studies involving pregnant women have not been conducted, dopamine precursors such as levodopa (also called L-Dopa) have been shown to cause problems in the offspring of animals. In these studies, pregnant animals received several times the dosage used in humans. This affected the baby’s growth both before and after birth. As a result, women who are pregnant or who may become pregnant are urged to consult their physician before taking dopamine precursors.

Dopamine precursors pass into breast milk and may cause side effects in nursing babies. They also may reduce the flow of breast milk. As a result, these drugs should not be used by women who are breastfeeding without a physician’s approval.

Child use issues

Studies have not been performed regarding the effect of dopamine precursors on children. As a result, parents are urged to consult a physician and discuss the benefits and potential risks of allowing their children to take dopamine precursors.

Elderly use issues

Elderly people are especially susceptible to the effects of dopamine precursors and may be more likely to experience side effects. As a result, elderly people are urged to consult a physician and discuss the benefits and potential risks of taking dopamine precursors.

Symptoms of dopamine precursor overdose

Patients should contact a physician immediately if they experience uncontrolled movements of the mouth, tongue, face, head, neck, arms and legs. Other symptoms for which patients should seek medical attention include:

  • Back and neck muscle spasms
  • Difficulty walking, especially starting to walk
  • Eye pain
  • Fast, irregular or pounding heartbeat
  • Increased shaking of the hands

Questions for your doctor

Patients may wish to ask their doctor the following questions related to dopamine precursors:
  1. Why do you suggest I take dopamine precursors to treat my condition?
  2. What are the alternative treatments available to me?
  3. Which type of dopamine precursor do you believe would be most effective for me?
  4. What are the side effects associated with this drug?
  5. Will I have to stop taking other medications while I am on this drug?
  6. Who can help me plan a proper diet while I’m on this medication?
  7. How soon after I start taking this drug should I begin to notice improvement?
  8. How long will I be required to take this medication?
  9. What should I do if I miss a dose of my drug?
  10. Is this drug safe for me if I’m pregnant or breastfeeding?
  11. Is this drug safe for my child/elderly parent?


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