LDOPA

Levodopa, also called L-DOPA, is a medication used primarily to treat Parkinson's disease and, in some cases, dopamine-responsive restless legs syndrome. It is a prodrug of dopamine that can cross the blood-brain barrier via amino acid transporters. After crossing into the brain, aromatic L-amino acid decarboxylase converts it to dopamine, replenishing depleted dopamine in the striatum and improving motor symptoms such as bradykinesia, rigidity, and tremor.

Because much of the drug is converted to dopamine outside the brain, levodopa is usually given with inhibitors of peripheral dopa decarboxylase, such as carbidopa or benserazide, to increase central availability and reduce peripheral adverse effects like nausea and orthostatic hypotension. In practice, combinations like carbidopa-levodopa (often marketed as Sinemet or Madopar) are standard therapy, and fixed-dose combinations with a COMT inhibitor (entacapone) exist as well.

Long-term use is associated with diminishing benefit and motor complications, including wearing-off and peak-dose dyskinesias, as well as fluctuations in its effect known as the on-off phenomenon. Non-motor side effects can include confusion, psychosis, sleep disturbances, and impulse control disorders. Levodopa can interact with vitamin B6 (pyridoxine) which enhances peripheral breakdown unless a dopa decarboxylase inhibitor is co-administered; it also has interactions with monoamine oxidase inhibitors, antipsychotics, and high-protein meals which can affect absorption.

History and context: Levodopa became the most effective symptomatic treatment for Parkinson's disease after its introduction in the 1960s and remains a central therapy, often used in combination with other antiparkinsonian drugs to optimize control of symptoms.