Dopamine Precursors

Carbidopa/levodopa
Levodopa (L-dopa) is an amino acid and a precursor of dopamine. As L-dopa is biosynthesized into dopamine, other enzymes (known as decarboxylases) begin to break down available dopamine. Therefore, to increase the length of time that dopamine remains active in the central nervous system, L-dopa may be combined with another medication known as carbidopa, which blocks the activity of decarboxylase (i.e., DC inhibitor). The addition of carbidopa also allows a decrease in the dosage level of levodopa thus minimizing potential side effects such as nausea and vomiting.

Carbidopa/levodopa is available as a combination drug known as Sinemet®. Both chemical agents are also available as separate medications. Sinemet® is available in several strengths that contain carbidopa and levodopa in varying ratios (e.g., 1:10 or 1:4). Controlled-release formulations, such as Sinemet® CR, are also available that prolong the action of L-dopa.

Dopamine precursors are taken orally and may be administered as needed or on a regular schedule. Physicians may initially recommend that levodopa medications be taken approximately one to two hours before bedtime on an empty stomach, if possible, to help increase absorption. Because protein interferes with the absorption of Sinemet®, it should not be taken at the same time that a high protein meal in consumed. Physicians may initially prescribe 100 milligrams a day (mg/day) of levodopa in combination with an appropriate ratio of carbidopa, gradually increasing the dose as necessary. Average effective doses of carbidopa/levodopa may range from 12.5/50 to 75/300 mg/day regular formulation or 25/100 to 100/400-mg/day sustained-release formulation.

Levodopa medications (particularly regular formulations) may not always alleviate symptoms for the entire night. Patients may have an "end-of-dose rebound" effect as the previous dose wears off, experiencing RLS symptoms during the middle of the night or early the next morning. Physicians may attempt to prevent "end-of-dose rebound" by prescribing the controlled-release formulation or recommending that a does be added in the middle of the night. In approximately 50% to 80% of patients, RLS symptoms may develop with increased intensity earlier in the day, such as in the early evening, in the afternoon hours, or even in the morning. This phenomenon, known as augmentation, may begin within a few months after levodopa therapy has been initiated. However, increasing overall dosage levels (e.g., in an attempt to reduce "end of morning rebound") may contribute to the problem. Augmentation may be worse in individuals with severe RLS who take their first dose of medication before 6 p.m. or whose higher daily doses of levodopa are equal to or more than 200 mg. It may become necessary to discontinue levodopa medications to end such augmentation.

Levodopa therapy has been shown to remain effective in patients with RLS for up to five to 10 years, with only minimal side effects (e.g., nausea and vomiting). In comparison, many individuals with Parkinson's disease who receive levodopa therapy often experience abnormal involuntary movements (dyskinesias), psychiatric problems, or other side effects. (It is important to note that individuals with Parkinson's disease typically require higher overall dosages of levodopa medications than dosages required for treatment of RLS.)

	Dopamine Agonists