levodopa

Levodopa is the cornerstone drug for Parkinson's disease, a condition where the brain cells that make dopamine slowly die, leaving movements slow, stiff, and tremulous. You cannot simply give dopamine itself because it cannot cross from the blood into the brain — so instead we give levodopa, its raw ingredient, which the brain can take in and convert into dopamine.

Levodopa is the immediate metabolic precursor of dopamine. Unlike dopamine, it crosses the blood–brain barrier using an amino acid transporter; once inside, the enzyme DOPA decarboxylase converts it to dopamine, replenishing the depleted signal in the brain's movement pathways. In other words, levodopa is a prodrug for dopamine.

It is almost always combined with a peripheral decarboxylase inhibitor such as carbidopa or benserazide. These do not cross into the brain, so they stop levodopa being converted to dopamine in the body before it reaches the brain — boosting how much reaches the brain and cutting peripheral side effects like nausea and low blood pressure.

Levodopa is highly effective at first, but over years the benefit becomes less smooth: doses wear off sooner, 'on–off' fluctuations appear, and involuntary movements (dyskinesias) emerge, reflecting the underlying progression of the disease and a shrinking therapeutic window.