Levodopa is an amino acid (chemical formula C9H11NO4) that is used as a prodrug to manage the symptoms of Parkinson’s disease. It is usually taken orally in the form of a pill.
Although discovered in 1911, it was 50 years later when an Austrian biochemist Oleh Hornykiewicz reported levodopa as an effective drug for Parkinson’s. After injecting into patients, he found a significant improvement in patients’ conditions. As there was no effective drug prior to levodopa discovery, it became a revolutionary new treatment for Parkinson’s. And even still today, it is considered as the ´´gold standard´´ for treating Parkinson’s symptoms.
Levodopa is very effective in treating the early motor problems of the disease, particularly stiffness and slow movement. Nearly 80% of patients get improvement in their symptoms after taking levodopa.
How does it Produce in the Brain?
Levodopa is naturally produced in the brain as a precursor of dopamine, a well-known neurotransmitter that is responsible for controlled body movement. It represents a key step in the pathway that synthesized dopamine in the brain.
In this pathway, levodopa is formed from the amino acid L-tyrosine, which is produced from phenylalanine obtained from food. This reaction is catalyzed by an enzyme called tyrosine hydrolase. Immediately after its formation, levodopa is metabolized to dopamine with the help of dopa decarboxylase enzyme. The newly formed dopamine is then taken up by neurons and distributed to different parts of the brain to perform its functions.
How does it Cause its Therapeutic Effects in Parkinson’s?
Dopamine depletion in the brain is the main reason why people develop Parkinson’s disease. Restoring its amount in the brain by using dopamine as a drug would have been an ideal treatment option. But unfortunately, this is not possible because dopamine can’t enter the brain without crossing a barrier called the blood-brain barrier. This barrier is important as it stops the entry of toxins and other pathogens from blood to the brain while allows the entry of water, oxygen and other substances that do not cause any harm to the brain.
Levodopa, on the other hand, can cross the blood-brain barrier and act locally by using the remaining healthy dopamine-producing neurons to synthesize dopamine. So it can be used as a prodrug to restore dopamine amount and thereby manage the symptoms of Parkinson’s disease.
However, the main problem with levodopa is that much of it is wasted in the blood before it reaches the brain. This is due to its breakdown caused by an enzyme – the same enzyme which turns levodopa to dopamine inside the brain. It is estimated that 95% of orally taken levodopa (when used alone) is wasted outside the brain. The presence of such a high dose in the blood can certainly cause some serious side effects.
In order to prevent its breakdown and avoid its side effects, it is used in a combination with another drug called carbidopa. Carbidopa acts by inhibiting the activity of the enzyme that metabolizes levodopa outside the brain and allows levodopa access to the brain without being wasted in the blood. It also reduces the side effects associated with levodopa use.
Following are the most commonly used drugs of this class:
- Rytary
- Sinemet
- Parcopa
- XP21279
What are its Side Effects?
Levodopa use is associated with a number of side effects in the body. Some of these effects develop slowly and are the major troublesome for a patient while others have acute effects and diminish after few weeks.
Following are the most common side effects caused by the use of levodopa therapy.
Dyskinesia – Uncontrolled Involuntary Movement
This is the most unpleasant side effect that appears within 2 years of using levodopa therapy, although in some patients, it may appear after 5 years.
It refers to the abnormal uncontrolled involuntary movements that mostly affect the arms, legs, and face. In this condition, the tremor becomes more aggressive and results in the wiggly movement.
Wearing-Off Effects
The key issue with levodopa is its fluctuations within the body. When a patient takes it, the symptoms improve. But after a short period of time, they reappear. This On-Off effect is not observed in patients using anti-Parkinson’s drugs other than levodopa.
The Off effect can appear without warning and is very uncomfortable for the patient. The slowness of movement becomes worse and the patient becomes unable to walk and freezes all of a sudden. Also, small movements like raising from a chair or rolling over bed become very difficult.
Nausea
The use of levodopa often causes nausea and vomiting in patients and these effects are caused when levodopa is used alone. They are improved when levodopa is used with carbidopa. These problems can also be prevented by using drug domperidone, a well-known dopamine antagonist.
Low Blood Pressure
Frequent use of levodopa is reported to widen blood vessels and leads to a fall in blood pressure. The patient experienced low blood pressure when changing position. For example, from lying to sitting or from sitting to standing. This is known as postural hypotension. When it happens, the patient starts to feel dizziness, blurred vision, fainting, and an unsteady feeling. In this situation, walking can be troublesome; the patient can easily fall, which could lead to serious injuries.
Psychological Effects
Repeated use of levodopa can produce some psychological effects similar to those appear in Schizophrenia like delusions and hallucinations. It can also cause insomnia or nightmares in some patients.
Disclaimer: The information shared here should not be taken as medical advice. The opinions presented here are not intended to treat any health conditions. For your specific medical problem, consult with your health care provider.
