Increasing the Dopamine Levels

Dopamine, itself, does not cross the blood-brain barrier. Therefore, it is administered as the precursor levodopa (Fig 1) in combination with carbidopa (Sinemet®).

Fig 1 The action of levodopa on the receiving cell

The action of carbidopa

Carbidopa blocks peripheral dopa decarboxylase, the enzyme that converts levodopa to dopamine.

With this combination, brain levodopa levels rise more significantly.

This drug combination was named Sinemet® – meaning ‘without emesis’ – because it decreases the side effects caused by peripheral dopamine, especially nausea and vomiting.

These slides show three therapeutic effects of levodopa.

Fig 2a This image shows the effect of levodopa early in the disease

Side effects of levodopa

The side effects of levodopa include:

  • Orthostatic hypotension
  • Nausea
  • Hallucinations
  • Peak-dose dyskinesias


Efficacy of levodopa

Levodopa is still considered the most efficacious treatment for PD.

Unfortunately, levodopa’s short duration of action necessitates increasingly frequent dosing as the disease progresses. Thus, doses eventually have to be taken as often as every 90 minutes.

Levodopa therapy is usually delayed until the patient’s symptoms interfere with their activities because after several years of therapy, levodopa is associated with predictable complications including:

  • Loss of efficacy before the next dose (wearing off)
  • Dyskinesias (unwanted movements of the head, shoulders or limbs)
  • ‘On-off’ periods (radical swings between functioning and nonfunctioning states)

Learning Bite

Levodopa is the most effective drug to treat PD. However, it should not be started until symptoms interfere with the patient’s activities and these symptoms are not controlled by dopamine agonists alone.

Amantadine and levodopa

Amantadine appears to act synergistically with levodopa and is often used in the treatment of early PD.

Recent reports suggest that amantadine reduces the dyskinesias that occur later in the disease.

Note: It is important that a patient takes PD medications strictly on time even when under medical care [9].