Levodopa is a prescription medication used to treat disorders of the central nervous system. The active ingredient is L-dopa, the precursor of a neurotransmitter that can cross the blood–brain barrier to reach the site of the disease. Parkinson’s disease is among the most common conditions for therapy with levodopa.
What is levodopa?
Parkinson’s disease is among the most common conditions for therapy with levodopa. Levodopa is also called L-dopa and is chemically, an amino acid and a derivative of phenylalanine. The chemical name of the compound is L-3,4-dihydroxy-phenylalanine 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 present 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 messengers in the body. These include dopamine, adrenaline, noradrenaline and melanin. L-dopa is transported to the nerve cells where further reaction takes place, for example to dopamine. Dopamine is formed after decarboxylation of L-dopa. This reaction occurs in the central nervous system (CNS), but also outside. For medication, the reaction should occur primarily in the CNS. For this reason, levodopa as a drug is predominantly combined with another component: a dopamine decarboxylase inhibitor. The corresponding preparations are called, for example, levodopa comp. or additionally identify this carboxylase inhibitor in the name.
Pharmacologic action
The first treatment trials with L-dopa were documented in 1961. The goal was to compensate for a deficiency of the neurotransmitter dopamine in the brain. Direct administration of dopamine was unsuccessful because dopamine does not enter the brain from the bloodstream. That is, 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, enters the brain after passing the blood-brain barrier and is converted to dopamine by the elimination of carbon dioxide (decarboxylation). In the bloodstream, L-dopa also reacts to form dopamine. 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, referred to as L-dopa late syndrome or L-dopa long-term syndrome. After a period of time that varies from individual to individual, a state is reached in which there are too few dopamine-providing cells and storage of dopamine is inadequate. The effect of L-dopa ebbs after two hours. If it is not replenished, gaps in effect (end-of-dose effects) become apparent. Furthermore, dopamine receptors respond to the non-continuous supply of dopamine. On the one hand, hyperexcitation is reflected as involuntary movement (dyskinesias); on the other hand, short-term decreased insensitivity with slowing, rigidity, or muscle spasms (motor fluctuations) occurs.
Medical use and application
The main indication for medication with levodopa is Parkinson’s disease. In this disease, a special network of nerve cells called the basal ganglia is affected and serves as the control center for movement. The presence of dopamine is required for the regulation of movement. Two areas associated with dopamine metabolism play a special role: the black matter (substantia nigra) and the so-called striatum. While dopamine is formed in the former, the striate body takes up dopamine and ensures its conversion into specific signals and their transmission. In this process, dopamine acts as a messenger substance (neurotransmitter). In Parkinson’s disease, cells in the black matter die, so that less dopamine is synthesized. Parkinson’s disease is one of the most common diseases of the nervous system. With increasing age, the disease occurs more frequently. Restless legs syndrome is also treated with levodopa in some cases.This neurological disorder is characterized by sensory disturbances in the legs or feet accompanied by involuntary movements. It is known that changes in dopamine metabolism play a significant role in this disorder. Levodopa leads to relief of the symptoms. Levodopa is also increasingly used in the treatment of Huntington’s disease. Huntington’s disease is a hereditary disorder that is still incurable. Patients show a disturbed emotional life and impaired control of muscles and facial expressions. In patients who experience muscle stiffness (rigor), medication with levodopa can bring about improvement.
Risks and side effects
Excessive doses may cause disturbances in movement (dyskinesia) or psychological problems (insomnia, hallucinations). Possible side effects include vomiting, nausea, and cardiovascular disturbances. Patients suffering from pheochromocytoma, severe hyperthyroidism, or narrow-angle glaucoma (form of glaucoma) should not take levodopa. There is also a particular risk in the case of cardiac arrhythmias, after a heart attack or gastrointestinal ulcers. In addition, there are numerous interactions with other drugs. Dopamine antagonists, substances that neutralize the acidity of gastric juice (antacids) and iron preparations reduce the effects of levodopa, as do nerve-dampening substances (neuroleptics), opioid painkillers and antihypertensive agents. Certain MAO inhibitors (MAO-B inhibitors), on the other hand, enhance the effect. If, on the other hand, MAO-A inhibitors are taken at the same time, this can result in an enormous increase in blood pressure. When starting therapy with levodopa, concomitant use of other medications should be conscientiously checked in any case.
