Levodopa is one of the main medications used to treat the symptoms of Parkinson’s disease, such as stiffness and slowness of movement. It’s naturally found in the body and is the precursor of dopamine, a neurotransmitter or signaling molecule that relays electric signals between nerve cells.

Levodopa can be used at all stages of Parkinson’s disease to replace the lost dopamine seen in these patients. It is available in many forms: as controlled or extended-release tablets (Rytary), as dispersible tablets that can be mixed with water, and as an intestinal gel (Duodopa) that is pumped via a tube surgically inserted into the intestine.

How levodopa works

After absorption in the gastrointestinal tract, levodopa is transported via the blood to the brain. Levodopa, unlike dopamine, can cross the blood-brain barrier and enter the brain, where it is converted into dopamine. This dopamine, subsequently, activates dopamine receptors and improves the function of movement control centers in the brain.

To avoid the breakdown of levodopa outside the brain, the treatment is usually given in combination with other medications such as carbidopa (Sinemet), entacapone (Stalevo) or tolcapone (Tasmar). These combination treatments allow more levodopa to reach the brain and help reduce its side effects, such as nausea and vomiting, by decreasing the required dose of medication.

Levodopa in clinical trials

There are more than 60 clinical trials that are currently recruiting patients with Parkinson’s disease to further study levodopa.

For example, a randomized, double-blind clinical study (NCT03541356) in Australia aims to evaluate the therapeutic efficacy of intranasal levodopa during off episodes.

In another study (NCT02480803), researchers are comparing the cost-effectiveness of intestinal levodopa with deep brain stimulation.

In Sweden, a study (NCT03419806) is investigating the different modes of levodopa administration and determining whether injecting levodopa directly into the blood is more effective than delivering it into the intestine via a tube, such as in the case of Duodopa.

Other information

Side effects of levodopa include nausea, vomiting, dry mouth, dizziness, low blood pressure, loss of appetite, and psychological and sleep problems. In some individuals, levodopa may cause confusion, hallucinations, or psychosis.

Levodopa’s effectiveness reduces over time. Long-term use of levodopa may cause patients to experience wearing off; in other words, the drug wears off before it’s time for the next dose. Long-term use may also result in spontaneous involuntary movements (dyskinesia), with some patients experiencing impulsive and compulsive behavior.

Patients are advised to take levodopa 30 to 60 minutes before meals because, in some cases, its absorption may be impeded by protein-rich foods such as eggs, meat, fish, cheese, and pulses. Abruptly stopping levodopa may cause withdrawal symptoms such as depression, anxiety, or pain.

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