From the Guidelines
The primary goal of pharmacotherapy in Parkinson's disease is to increase dopamine levels or dopaminergic activity in the brain, particularly in the nigrostriatal pathway. Parkinson's disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to dopamine deficiency in the striatum. This dopamine deficiency creates an imbalance with other neurotransmitters, resulting in the classic motor symptoms of Parkinson's. The main pharmacological approaches include levodopa (a dopamine precursor that crosses the blood-brain barrier and converts to dopamine), dopamine agonists, MAO-B inhibitors, and COMT inhibitors that prevent dopamine breakdown 1.
Key Considerations
- The use of levodopa may be associated with impaired nutritional status and risk for malnutrition, as well as metabolic effects such as hyperhomocysteinemia 1.
- Increasing doses of levodopa and levodopa equivalent doses have been found to be related to increased risk for malnutrition 1.
- The true relationship between levodopa use and weight loss needs to be determined, as it is unknown whether higher levodopa use induces weight loss, or patients with more severe disease receive higher doses of levodopa per kg body weight 1.
Pharmacological Approaches
- Levodopa is a dopamine precursor that crosses the blood-brain barrier and converts to dopamine.
- Dopamine agonists, such as pramipexole and ropinirole, mimic the action of dopamine in the brain.
- MAO-B inhibitors, such as selegiline and rasagiline, prevent the breakdown of dopamine.
- COMT inhibitors, such as entacapone and tolcapone, also prevent the breakdown of dopamine.
Conclusion is not allowed, so the answer just ends here.
From the FDA Drug Label
Rationale for the Use of a Selective Monoamine Oxidase Type B Inhibitor in Parkinson’s disease Many of the prominent symptoms of Parkinson’s disease are due to a deficiency of striatal dopamine that is the consequence of a progressive degeneration and loss of a population of dopaminergic neurons which originate in the substantia nigra of the midbrain and project to the basal ganglia or striatum 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 of pharmacotherapy in Parkinson's disease regarding dopamine levels is to increase the net amount of dopamine available by blocking its catabolism through MAO-B inhibition, thereby increasing the pool of dopamine 2.
- Key points:
- Parkinson's disease is characterized by a deficiency of striatal dopamine.
- MAO-B inhibition increases the net amount of dopamine available.
- This is achieved by blocking the catabolism of dopamine.
From the Research
Goal of Pharmacotherapy in Parkinson's Disease
The goal of pharmacotherapy in Parkinson's disease is to manage the symptoms of the disease, primarily by modulating dopamine concentrations in the brain.
- The main objective is to compensate for the deficit in dopamine found in Parkinson's disease patients 3, 4, 5.
- Dopaminergic pharmacotherapy, including levodopa and other dopaminergic drugs, is used to replace dopamine in the brain 4, 6.
- The ideal pharmacological drug for Parkinson's disease should provide symptomatic relief and have a safe side-effect profile 3.
Dopamine Replacement Therapy
Dopamine replacement therapy is a well-established treatment for Parkinson's disease, based on the deficiency of dopamine in the brain.
- Levodopa is the most effective treatment available and is used as a dopamine precursor 3, 7.
- Other dopaminergic drugs, such as dopamine agonists and monoamine oxidase B inhibitors, are also used to modulate dopamine concentrations in the brain 4, 5.
- The goal of dopamine replacement therapy is to restore normal motor function and alleviate symptoms such as tremor, rigidity, and bradykinesia 3, 4.