Active Ingredients

Levodopa – Effect, Application & Risks

Levodopa

Levodopa is a prescription drug used to treat disorders of the central nervous system . The active ingredient is L-Dopa , the precursor of a messenger substance that can cross the blood- brain barrier and thus reach the site of the disease. Parkinson’s disease is one of the most common clinical pictures for therapy with levodopa.

What is levodopa?

Levodopa is also called L-Dopa and chemically it is an amino acid and a derivative of phenylalanine . The chemical name of the compound is L-3,4-dihydroxyphenylalanine or 2-amino-3-(3,4-dihydroxyphenyl)propanoic acid.

The human body synthesizes L-Dopa from the amino acid tyrosine . This is formed from the essential amino acid phenylalanine, which is contained in many foods. After hydroxylation of tyrosine, L-DOPA is formed. It represents the precursor for the synthesis of various substances that act as hormones and messenger substances in the body. These include dopamine , adrenaline , norepinephrine , and melanin .

L-Dopa is transported into the nerve cells and there the further reaction takes place, for example to dopamine. Dopamine is formed after decarboxylation of L-Dopa. This reaction takes place in the central nervous system (CNS), but also outside of it. For the medication, the reaction should primarily take place in the CNS. Therefore, levodopa as a drug is mainly combined with another ingredient: a dopamine decarboxylase inhibitor. The corresponding preparations are called, for example, Levodopa comp. or also indicate this carboxylase inhibitor in the name.

Pharmacological action

First attempts at treatment with L-Dopa were documented in 1961. The aim was to compensate for a lack of the neurotransmitter dopamine in the brain . Giving dopamine directly has not been successful because dopamine does not get to the brain from the bloodstream . This means that while L-DOPA can pass through the natural, selectively permeable barrier between the brain (central nervous system, CNS) and the bloodstream, it remains impermeable to dopamine. Levodopa, as a precursor of dopamine, penetrates the brain after passing the blood-brain barrier and is converted into dopamine by splitting off carbon dioxide (decarboxylation).

L-Dopa also reacts to form dopamine in the bloodstream. Further developments of the drug prevent this effect by combining L-Dopa with a dopamine decarboxylase inhibitor. Benserazide and carbidopa are such inhibitors that prevent the conversion of L-dopa to dopamine outside the brain.

The therapeutic effect of levodopa is excellent within the first three to seven years. After that, side effects set in, which are known as L-Dopa late syndrome or L-Dopa long-term syndrome. After an individually variable period of time, a state is reached in which there are too few dopamine-providing cells and storage of dopamine is insufficient. The effects of L-Dopa wear off after two hours. If it is not subsequently supplied, there will be gaps in effectiveness (end-of-dose effects).

Furthermore, the dopamine receptors react to the non-continuous supply of dopamine. On the one hand, an overreaction is reflected as an involuntary movement (dyskinesia), on the other hand, a short-term reduced insensitivity with slowing down, stiffness or muscle cramps (motor fluctuation) occurs.

Medical Application & Use

The main indication for medication with levodopa is Parkinson’s disease. This disease affects a special network of nerve cells called the basal ganglia , which serves as the control center for movement. The regulation of movement requires the presence of dopamine.

Two areas related to dopamine metabolism play a special role: the black substance (substantia nigra) and the so-called striped body ( striatum ). While dopamine is formed in the former, the striped body absorbs dopamine and ensures that it is converted into certain signals and passed on. Dopamine acts as a messenger substance ( neurotransmitter ). In Parkinson’s disease, cells in the black matter die off so less dopamine is synthesized. Parkinson’s disease is one of the most common diseases of the nervous system. With age, the disease becomes more common.

Restless Legs Syndrome is also sometimes treated with levodopa. Characteristic of this neurological disease are sensory disturbances in the legs or feet , which are accompanied by involuntary movements. It is known that changes in dopamine metabolism play a significant role in this disorder. Levodopa relieves the symptoms.

Levodopa is also increasingly being used in the treatment of Huntington ‘s disease. Huntington’s disease is still an incurable hereditary disease. The patients show a disturbed emotional life and limited control of muscles and facial expressions . Medication with levodopa can bring about an improvement in patients with muscle stiffness ( rigor ).

Risks & side effects

Doses that are too high can cause movement disorders (dyskinesia) or psychological problems ( insomnia , hallucinations ). Possible side effects include vomiting , nausea and cardiovascular problems .

Patients suffering from pheochromocytoma , severe hyperthyroidism or angle-closure glaucoma (type of glaucoma ) should not take levodopa. There is also a particular risk of cardiac arrhythmia , after a heart attack or gastrointestinal ulcers .

In addition, there are numerous interactions with other drugs. Dopamine antagonists, substances that neutralize the acidity of the gastric juice ( antacids ) and iron preparations reduce the effects of levodopa, as do nerve-depressing substances ( neuroleptics ), opioid painkillers and antihypertensive substances. Certain MAO inhibitors (MAO-B inhibitors), on the other hand, increase the effect. If, on the other hand, MAO-A inhibitors are taken at the same time, this can result in an enormous rise in blood pressure. When starting therapy with levodopa, the simultaneous use of other medications should always be carefully checked.

Lisa Newlon
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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.