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Levodopa (carbidopa/levodopa)

Although Parkinson's disease is characterized by a loss of brain cells that contain and release the brain chemical (or neurotransmitter) dopamine, simple replacement of dopamine by pill or intravenously is not effective because dopamine is not transported to the brain. However, levodopa (a chemical precursor of dopamine) is transported to the brain and is then transformed into dopamine. The introduction of levodopa (or L-dopa) more than 40 years ago revolutionized treatment of Parkinson's disease. For most individuals, treatment with levodopa reduces the motor symptoms. It remains the most effective treatment for Parkinson's disease.

After being absorbed in the gastrointestinal tract, levodopa is transported to brain cells, where it is transformed into dopamine. It is subsequently released by brain cells and activates dopamine receptors, allowing for improved function of the movement control centers of the brain. Since blood enzymes, called "amino acid decarboxylases," would break down most levodopa before it reached the brain, levodopa is always combined with an enzyme inhibitor called carbidopa (or benserazide in Europe). The trade names of this combination are called Sinemet® or Atamet®.   Parcopa® is a formulation that easily dissolves in the mouth.

Although levodopa remains the single most effective treatment for Parkinson's disease, treatment over a number of years may lead to variability in an individual's response to treatment, called "motor fluctuations." The fluctuating response to levodopa can be broadly divided into "on" and "off" periods. During an "on" period, a person can move with relative ease often with reduced tremor and stiffness. "Off" periods describe those times when a person has greater difficulty with movement. A common time for a person with Parkinson's disease to experience an "off period" is just prior to taking the next dose of levodopa, and this experience is called "wearing off." Another form of motor fluctuation is uncontrolled writhing or other abnormal movement of the body or a limb, which is called "dyskinesia." About 40% of people treated with levodopa will develop motor fluctuations within six years of treatment.

Levodopa is rapidly absorbed from the small intestine. Food (in particular, protein-rich food) delays its absorption by the gastrointestinal tract and delivery into the bloodstream. When levodopa is taken 30-60 minutes before a meal, many people notice an improvement beginning after about 30 minutes. Most people with Parkinson's disease note that benefit of levodopa lasts about 3-5 hours, but the duration of benefit may range from as long as a day to as short as an hour.

Levodopa is also available as a long acting or "controlled-release" (CR, ER, or SR) formulation. Controlled release levodopa provides a longer duration of action by increasing the time it takes for the gastrointestinal tract to absorb levodopa. However, because the controlled release formulation only allows 70% of the levodopa to be absorbed by the gastrointestinal tract, in order to obtain the same benefit, it may be necessary to increase the levodopa (measured in mg) when a person is switched from standard (or immediate-release) levodopa to controlled-release levodopa.

Levodopa preparations

Standard release preparations:

levodopa/carbidopa (Sinemet®, Atamet®) available in 10/100, 25/100, or 25/250 tablets

Parcopa® is an accelerated release preparation available in 10/100, 25/100, or 25/250 tablets

Extended release preparations:

levodopa/carbidopa (Sinemet CR®) 25/100 or 50/200 tablets

Side effects

Side effects include nausea, vomiting, dry mouth, dyskinesias, and dizziness. In some individuals, levodopa may cause confusion, hallucinations, or psychosis. Motor fluctuations develop in about 40% of people treated for 4-6 years.

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