How levodopa works
Levodopa improves the slowed mobility and stiffness in patients with Parkinson’s disease by increasing the concentration of dopamine in the brain as a precursor to dopamine.
The messenger substance dopamine is used in the brain to transmit signals between nerve cells – especially those involved in controlling movement. An important region for this is the “substantia nigra” (Latin for “black substance”) in the midbrain. If dopamine-producing nerve cells die there, Parkinson’s disease occurs.
Dopamine is produced in the body from the natural amino acid (protein building block) tyrosine. This is converted into the intermediate levodopa and then further into dopamine.
Dopamine itself is not administered to Parkinson’s patients because it cannot cross the blood-brain barrier. It would also lead to many peripheral side effects (affecting the body).
These two problems are avoided with levodopa therapy. It is a precursor, so it does not work at first, can cross the blood-brain barrier and is then quickly converted to dopamine in the brain.
As neither substance is able to cross the blood-brain barrier, levodopa alone enters the central nervous system where it is converted into dopamine.
Absorption, breakdown and excretion
After ingestion, levodopa is absorbed into the blood in the upper section of the small intestine. The highest blood levels are reached after about an hour if taken on an empty stomach (fasting).
Levodopa reaches the brain via the bloodstream, where it is converted into dopamine and can act on its docking sites (receptors). It is then broken down in the same way as natural dopamine.
In the case of medicines that have entacapone added in addition to levodopa and benserazide, the latter counteracts the breakdown of dopamine. This extends the duration of action of the medication.
Levodopa is quickly broken down and excreted. Approximately one and a half hours after ingestion, half of the active ingredient has already left the body. The active ingredient must therefore be taken throughout the day.
When is levodopa used?
One of the areas of application for levodopa is Parkinson’s disease (shaking palsy). It is accompanied by tremors, muscle rigidity and lack of movement (bradykinesia) or immobility (akinesia).
In contrast, Parkinson’s symptoms that occur as a result of treatment with drugs such as neuroleptics (antipsychotics) should not be treated with levodopa. Instead, if the symptoms are severe, the causative drug is changed if possible.
The second area of application for levodopa is restless legs syndrome (RLS), although an iron deficiency or other triggers must first be ruled out.
As the symptoms are only alleviated symptomatically in both cases, treatment is always long-term.
Another area of application is, for example, the very rare hereditary disease Segawa syndrome, a movement disorder affecting the whole body due to a genetic defect. However, the treatment is carried out outside of the approval (“off-label use”).
How levodopa is used
The active substance is usually administered as a tablet. The total daily dose must not exceed 800 milligrams of levodopa (in combination with benserazide or carbidopa) and is administered in four doses throughout the day in order to achieve blood levels that are as constant as possible.
The dosage is increased “gradually”, i.e. slowly until the optimal amount of active ingredient is found. This also reduces the side effects that occur more frequently at the beginning.
The dosage is also determined individually for the treatment of restless legs syndrome.
What side effects does levodopa have?
The pronounced side effects of levodopa on the cardiovascular system and the gastrointestinal tract are reduced by combining it with benserazide or carbidopa.
Nevertheless, more than ten percent of patients experience loss of appetite, sleep disorders, depression, nausea, vomiting, diarrhea and a change in liver enzyme levels. After prolonged treatment, a so-called “ON-OFF phenomenon” can occur, in which the patient’s mobility caused by levodopa quickly turns into immobility.
Such “ON-OFF phenomena” are usually observed after about five years of levodopa therapy and are most likely due to progression of the disease.
What should be considered when taking levodopa?
Contraindications
Levodopa must not be taken if:
- skeletal development not yet complete
- severe endocrine dysfunction (such as hyperthyroidism or Cushing’s syndrome)
- severe metabolic, liver or bone marrow disorders
- severe kidney disease
- severe heart disease
- Psychosis or schizophrenia
- narrow-angle glaucoma
Interactions
Taking levodopa with other active substances can lead to interactions that affect the effectiveness of the treatment.
Certain drugs for depression that slow down the breakdown of endogenous messenger substances in the brain (monoamine oxidase/MAO inhibitors) can also lead to life-threatening high blood pressure crises. For this reason, levodopa therapy should not be started until at least two weeks after discontinuation of the MAO inhibitor.
Other circulation-stimulating agents (such as agents for asthma therapy and ADHD treatment) can also overload the cardiovascular system. The therapy should therefore be closely monitored by a doctor. The same applies to the combination of high blood pressure medication and levodopa.
As levodopa is absorbed in the intestine like amino acids (protein building blocks), the simultaneous intake of a protein-rich meal (e.g. meat, eggs) can hinder the absorption of the active substance.
Age restriction
Levodopa and benserazide combination preparations are approved from the age of 25. Levodopa in combination with carbidopa from the age of 18.
Pregnancy and lactation
In animal studies, levodopa showed a harmful effect on the offspring. There are no indications of significantly increased specific risks from observations in humans to date. If treatment is clearly indicated, levodopa should be combined with carbidopa during pregnancy.
In practice, breastfeeding is acceptable under moderate-dose combination therapy with levodopa and carbidopa with good observation of the child and with reservations. Attention should be paid to any side effects and sufficient weight gain in the child.
How to obtain medication with levodopa
All medicines containing the active ingredient levodopa are available on prescription in Germany, Austria and Switzerland.
How long has levodopa been known?
Levodopa was first used in the 1950s by Arvid Carlsson, who later won the Swedish Nobel Prize, to treat animals with Parkinson’s disease. In the following decade, levodopa was also tested on humans.
The field of application was extended, for example to the treatment of manganese poisoning and European sleeping sickness. Levodopa was officially approved for the treatment of Parkinson’s disease in 1973.
The active ingredient can also be used for restless legs syndrome. As patent protection has now expired, there are now numerous generics containing levodopa.
Technical innovations have now made it possible to administer a levodopa-containing gel directly into the small intestine using a special pump. This makes it easier to treat “ON-OFF phenomena”.
