From the Guidelines
In Parkinson's disease, the primary goal is to increase dopamine activity in the brain, not block it, by using medications that either replace dopamine or mimic its effects, such as levodopa, dopamine agonists, MAO-B inhibitors, and COMT inhibitors. The condition results from the progressive loss of dopamine-producing neurons in the substantia nigra, leading to motor symptoms like tremor, rigidity, and bradykinesia. According to a study published in 2018 1, levodopa is the gold standard treatment, as it crosses the blood-brain barrier and converts to dopamine. However, it's essential to note that levodopa use can cause metabolic effects, including weight loss, and may be associated with impaired nutritional status and risk for malnutrition, as well as hyperhomocysteinemia, which can be mitigated with vitamin B supplementation 1.
Other medications, such as dopamine agonists like pramipexole (Mirapex) or ropinirole (Requip), directly stimulate dopamine receptors, while MAO-B inhibitors like selegiline (Eldepryl) or rasagiline (Azilect) prevent dopamine breakdown, and COMT inhibitors like entacapone (Comtan) extend levodopa's effectiveness. Treatment typically starts with lower doses that increase gradually to minimize side effects, such as dyskinesias (involuntary movements) that can occur with long-term levodopa use. Another study published in 2018 1 highlights the importance of monitoring body weight and vitamin status in PD patients, as weight loss and gain can occur, and low vitamin D levels have been associated with the risk of developing PD.
Key considerations in managing Parkinson's disease include:
- Gradually increasing medication doses to minimize side effects
- Monitoring body weight and adjusting treatment accordingly
- Assessing and addressing vitamin deficiencies, particularly vitamin D and B
- Regularly evaluating the patient's response to treatment and adjusting the medication regimen as needed to optimize dopamine activity and minimize complications.
From the FDA Drug Label
MAO-B inhibition may be useful in this setting because, by blocking the catabolism of dopamine, it would increase the net amount of dopamine available (i.e., it would increase the pool of dopamine).
The goal in Parkinson's disease is to increase dopamine secretion or more specifically, to increase the net amount of dopamine available in the brain. This is achieved by blocking the catabolism of dopamine through MAO-B inhibition, rather than directly blocking dopamine secretion. Key points include:
- Increasing dopamine availability: MAO-B inhibition increases the net amount of dopamine available.
- Blocking dopamine catabolism: This is the mechanism by which MAO-B inhibitors like selegiline work to increase dopamine levels 2, 2.
From the Research
Parkinson's Disease Treatment
To address the question of whether to increase dopamine secretion or block it in Parkinson's disease, we need to understand the underlying pathology and treatment approaches. Parkinson's disease is characterized by a deficiency of dopamine, primarily due to the loss of dopaminergic neurons in the substantia nigra 3, 4.
Dopamine Replacement Therapy
The main therapeutic strategy for Parkinson's disease involves dopamine replacement therapy, which aims to increase dopamine levels in the brain. This can be achieved through the use of levodopa, dopamine agonists, and monoamine oxidase B (MAO-B) inhibitors 4, 5. Levodopa is a precursor to dopamine and is converted into dopamine in the brain, thereby increasing dopamine levels. Dopamine agonists mimic the action of dopamine and directly stimulate dopamine receptors.
Increasing Dopamine Secretion
Increasing dopamine secretion is a key approach in the treatment of Parkinson's disease. This can be achieved through the use of medications such as levodopa, dopamine agonists, and MAO-B inhibitors, which increase the availability of dopamine in the brain 3, 4, 5, 6. For example, rasagiline, a novel MAO-B inhibitor, has been shown to increase dopamine levels and improve motor symptoms in patients with Parkinson's disease 5.
Blocking Dopamine
In some cases, blocking dopamine may be necessary to manage certain symptoms of Parkinson's disease, such as dyskinesias. However, this approach is not typically used as a primary treatment strategy for Parkinson's disease. Instead, medications that block dopamine receptors, such as antipsychotics, may be used to manage psychosis or other non-motor symptoms in patients with Parkinson's disease.
Key Points
- Parkinson's disease is characterized by a deficiency of dopamine.
- Dopamine replacement therapy is the main therapeutic strategy for Parkinson's disease.
- Increasing dopamine secretion is a key approach in the treatment of Parkinson's disease.
- Medications such as levodopa, dopamine agonists, and MAO-B inhibitors are used to increase dopamine levels in the brain.
- Blocking dopamine may be necessary to manage certain symptoms, but is not a primary treatment strategy for Parkinson's disease.
Some of the key medications used to treat Parkinson's disease include:
- Levodopa
- Dopamine agonists (e.g. ropinirole, pramipexole)
- MAO-B inhibitors (e.g. rasagiline, selegiline)
- COMT inhibitors (e.g. tolcapone, entacapone)
- Amantadine
- Anticholinergic drugs
These medications can be used alone or in combination to manage the symptoms of Parkinson's disease, and the choice of medication will depend on the individual patient's needs and response to treatment 3, 4, 5, 6, 7.