How does L-DOPA treat the symptoms of Parkinson’s disease?

Answer: L-DOPA restores dopamine that is lost in Parkinson’s disease.

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Parkinson's disease is a movement disorder characterized by a resting tremor, difficulty initiating movement, and a slow, shuffling gait. It is incurable, and although there are theories about how the pathology occurs such as the Braak theory, there is still much debate as to how it occurs.

The loss of dopamine producing cells in the substantia nigra leads to a decrease in dopaminergic innervation of the striatum. This is believed to produce the major motor symptoms of Parkinson's disease. There are changes in the neuronal circuitry that results in a loss of regulation of normal output of the medium spiny neurons (MSNs) in the striatum. This dysregulation leads to poor motor control.

However, long term exposure to L-DOPA can lead to uncontrolled movements, called dyskinesia. It is unknown how these motor fluctuations (L-DOPA induced dyskinesias) occur. The dyskinesias are characterized by ballistic swinging of the limbs and distortion of facial muscles.

A combination levodopa and carbidopa drug mixture is given as a therapy to alleviate the motor symptoms. Levodopa is the biological precursor to dopamine, while carbidopa is a peripheral inhibitor of DOPA decarboxylase. The combination is an oral formulation.

Dopamine itself cannot cross the blood-brain barrier, while levodopa can. Once inside the brain, levodopa is converted into dopamine by the enzyme dopa decarboxylase.

Motor function is usually restored once dopamine is restored in the striatum. The effect is rapid, with restoration of normal movement within the hour. This restoration of normal activity is described in Awakenings, an autobiographical account by the neurologist Oliver Sacks as he treated patients with L-DOPA.