Parkinson’s disease is a progressive brain disorder that affects over 10 million people around the world. The most common symptoms of this disease include slowness of movement, rigidity, tremor, and balance problem. These symptoms appear when the brain lost a certain group of cells that produce dopamine, a neurotransmitter responsible for controlled body movement.
Medication is the most effective way of dealing with Parkinson’s disease. There have been developed drugs that not only help to treat the symptoms but also improve the overall quality of life. These drugs are specifically designed to restore the dopamine levels in the brain.
These can be divided into the following 6 main classes:
- Levodopa
- Dopamine Agonists
- MAO-B Inhibitors
- COMT Inhibitors
- Muscarinic Receptor Antagonists
- Amantadine
1. Levodopa
Levodopa is used as first-line therapy in Parkinson’s disease. It is an amino acid that produced in the brain as a precursor of dopamine.
It is very effective in treating the early motor problems of the disease, particularly the slowness of movement and rigidity. Nearly 80% of patients get improvement in their symptoms after taking levodopa.
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 called the dopa decarboxylase, the same enzyme that metabolizes levodopa to dopamine inside the brain.
In order to prevent its breakdown outside the brain, 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
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 a few weeks.
The most common side effects include dyskinesia (an uncontrolled involuntary movement), nausea, low blood pressure, insomnia and some psychological effects like hallucinations and delusions.
2. Dopamine Agonists
This class of drugs is prescribed for patients under 60 years of age or for those whose symptoms are not well-controlled by levodopa. In some patients, dopamine agonists are used alone. In others, they are used in a combination with levodopa.
Dopamine agonists can readily cross the blood-brain barrier and act locally by binding to dopamine receptors found on the neurons. In other words, they act like dopamine in the brain.
Dopamine agonists have some advantages that preferred them over other Parkinsonian’s drugs like levodopa. For example; they do not need enzymatic reactions for their activities, nor they required other transport substances for reaching the brain. Also, they do not produce any toxic metabolites.
Following are the common dopamine agonists that are used in Parkinson’s disease.
- Bromocriptine
- Pergolide
- Ropinirole
- Pramipexole
- Rotigotine
- Apomorphine
Dopamine agonists are associated with a number of side effects in the body. Mental disturbances are more common and patients can experience hallucinations, confusion, and delusions. These problems typically appear earlier in older patients and can be managed with antipsychotic drugs.
Gastrointestinal effects, cardiovascular effects, and other miscellaneous effects (like headaches, nasal congestion, and abnormal sleep) are linked to the used of dopamine agonists.
3. MAO-B Inhibitors
Monoamine oxidase-B (MAO-B) inhibitors are usually prescribed when the patient’s symptoms are not under control with levodopa/carbidopa medication. These drugs inhibit the actions of the enzyme involved in the breakdown of dopamine in the brain. By doing so, they increase the levels of dopamine up to 70% in the brain and improve the motor symptoms.
The main MAO-B inhibitors are:
- Safinamide
- Selegiline
- Rasagiline
Most often these drugs are used as adjunct therapy because they have minor therapeutic effect when used alone. Laboratory experiments in animals suggest that the drug selegiline may have the ability to reduce Parkinson’s progression. However, data from human clinical trials shows inconsistent results.
The most common problems associated with the use of MAO-B inhibitors include nausea, sleeping problems, falls, and uncontrolled movements.
4. COMT Inhibitors
COMT inhibitors are very effective in treating the motor symptoms and are often used as adjunct therapy to levodopa/carbidopa. These drugs work by protecting levodopa from the action of an enzyme called COMT (Catechol-O-methyltransferase), which degrades levodopa immediately after entering the blood.
COMT inhibitors efficiently bind and inhibit the action of COMT enzyme and thereby provide a continuous release of levodopa into the blood so that much of it is delivered to the brain without being degraded.
Following are the types of COMT inhibitors:
- Entacapone
- Tolcapone
- Opicapone
COMT inhibitors come with some side effects that include confusion, hallucination, diarrhea, constipation, sleeping problem, and vomiting. They may also cause liver toxicity in patients.
5. Muscarinic Receptor Antagonists
These were among the first available treatment for Parkinson’s disease and were frequently used before the discovery of levodopa. In fact, they are still used to treat motor symptoms like tremor and rigidity. However, they are not effective for treating the slowness of movement.
Examples of muscarinic receptors antagonists drugs include:
- Trihexyphenidyl
- Benztropine
- Orphenadrine
- Biperiden
These drugs are usually prescribed for those Parkinson’s patients who receive antipsychotic drugs. The most common side effects associated with the use of these drugs include constipation, urinary retention, dry mouth, and impaired vision. Their use can also cause dementia in patients.
6. Amantadine
This antiviral drug was accidentally discovered to be beneficial in Parkinson’s disease in 1969. Its use may improve symptoms like slow movements and stiffness in patients with early stage of the disease. In the later stage of the disease, it is more effective in treating dyskinesia caused by prolonged use of levodopa.
The exact mechanism of action of amantadine is still unknown. The common side effects include agitation, insomnia, constipation, hallucinations, dizziness, and dry mouth.
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.
