Pharmacology · Dopaminergic antiparkinson agents (levodopa and amantadine)
Levodopa + carbidopa !
The most effective treatment for Parkinson symptoms. Levodopa becomes dopamine in the brain; carbidopa stops it being wasted in the rest of the body.
Updated 2026-11-01
Also called: Carbidopa-levodopa, Co-careldopa
The figure shows carbidopa bound to pig DOPA decarboxylase (with its cofactor PLP); the human enzyme is very similar. Carbidopa blocks this enzyme outside the brain.
Mechanism of action
Levodopa, the amino acid precursor of dopamine, crosses the blood-brain barrier on amino acid carriers and is decarboxylated to dopamine in the remaining dopaminergic terminals of the striatum. Given alone, most of it would be turned into dopamine in the gut and blood, causing nausea and hypotension. Carbidopa inhibits aromatic amino acid decarboxylase but does not enter the brain, so it protects levodopa only in the periphery.
- Carbidopa blocks DOPA decarboxylase outside the brain
- More levodopa crosses the blood-brain barrier
- Striatal terminals convert levodopa to dopamine
- Dopamine receptors are stimulated: less slowness and rigidity
Pharmacokinetics
- Absorption
- Absorbed in the small intestine by amino acid transporters; protein-rich meals and iron reduce absorption
- Metabolism
- Decarboxylation (blocked outside the brain by carbidopa) and methylation by COMT
- Half-life
- Levodopa about 50 minutes alone, about 1.5 hours with carbidopa
- Onset and duration
- Benefit after the first doses; the effect of each dose shortens as the disease advances
Indications
- Parkinson disease (motor symptoms) Parkinson disease →
- Parkinsonism after encephalitis or carbon monoxide or manganese poisoning
Adverse effects
Common
- Nausea, vomiting and loss of appetite
- Dyskinesias (involuntary movements), earlier and at lower doses than with levodopa alone
- Orthostatic hypotension and dizziness
- Motor fluctuations: end-of-dose wearing-off and on-off episodes
- Dark saliva, urine or sweat (harmless)
Contraindications
- Narrow-angle glaucoma
- Nonselective MAO inhibitors (stopped at least two weeks before)
- Hypersensitivity to either component
Key interactions
- Nonselective MAO inhibitors (phenelzine, tranylcypromine)
- Hypertensive reactions; contraindicated
- Antipsychotics (phenothiazines, butyrophenones, risperidone), metoclopramide, isoniazid
- Reduce the effect of levodopa
- Iron salts (including multivitamins with iron)
- Chelate levodopa and carbidopa and lower their absorption
- High-protein meals
- Amino acids compete for absorption and delay the effect
- Selegiline
- Can cause severe orthostatic hypotension
What is monitored
- Motor response, timing of off periods and dyskinesias (symptom diary)
- Blood pressure lying and standing
- Mood, hallucinations, impulse-control behaviours and daytime sleepiness
- Intraocular pressure in wide-angle glaucoma; periodic skin checks for melanoma
- Liver, blood, cardiovascular and kidney function during long treatment
Administration and safety
- Given at regular times every day; delays cause off periods
- Never stopped abruptly, including before surgery or when nil by mouth; the team plans how to continue it
- Immediate-release and extended-release forms are not interchangeable one for one
- Spacing it from protein-rich meals and iron supplements can improve absorption
Nursing care
- Check orthostatic blood pressure and fall risk, especially when starting
- Record on and off times and involuntary movements
- Ask about hallucinations, gambling, shopping or sexual urges and sudden sleep
- Watch for fever, rigidity and confusion if doses are missed or reduced
- Explain that dark urine or sweat is expected
Pregnancy and breastfeeding
There are no adequate studies in pregnancy; levodopa crosses the placenta. Use is a specialist decision.
Test yourself
Think of the answer, then tap the question to see it.
Why does adding carbidopa allow a smaller levodopa dose with less nausea?
It blocks peripheral DOPA decarboxylase, so less levodopa is turned into dopamine in the gut and blood and more reaches the brain.
What is the «wearing-off» phenomenon?
Return of Parkinson symptoms before the next dose is due, as the effect of each dose shortens with disease progression.
Which type of glaucoma contraindicates levodopa + carbidopa?
Narrow-angle glaucoma.
What can happen if levodopa is stopped suddenly?
High fever, rigidity and confusion resembling neuroleptic malignant syndrome, and severe worsening of parkinsonism.
Related drugs
Related conditions
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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - CARBIDOPA AND LEVODOPA tablet (DailyMed (U.S. National Library of Medicine), 2026); Levodopa and Carbidopa: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.