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:

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.