From the FDA Drug Label
Current evidence indicates that symptoms of Parkinson’s disease are related to depletion of dopamine in the corpus striatum. However, levodopa, the metabolic precursor of dopamine, does cross the blood-brain barrier, and presumably is converted to dopamine in the brain. This is thought to be the mechanism whereby levodopa relieves symptoms of Parkinson’s disease
The goal of pharmacological therapy in Parkinson's disease regarding dopamine receptors in presynaptic and postsynaptic receptors is to increase dopaminergic activity by:
- Converting levodopa to dopamine in the brain, which then acts on dopamine receptors to relieve symptoms of Parkinson's disease 1
- Inhibiting the breakdown of dopamine by monoamine oxidase (MAO) type B, allowing more dopamine to be available to act on dopamine receptors 2 Key points:
- Levodopa is converted to dopamine in the brain, which then acts on dopamine receptors to relieve symptoms of Parkinson's disease
- Carbidopa inhibits the decarboxylation of levodopa outside the brain, allowing more levodopa to be available for conversion to dopamine in the brain 1, 3
- Selegiline inhibits MAO type B, allowing more dopamine to be available to act on dopamine receptors 2
From the Research
The goal of pharmacological therapy in Parkinson's disease is to increase dopamine activity in the brain by targeting presynaptic and postsynaptic dopamine receptors, not to block them. Parkinson's disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra, leading to dopamine deficiency 4. Treatment aims to restore dopamine function through several approaches, including the use of levodopa, a dopamine precursor that crosses the blood-brain barrier and converts to dopamine, typically combined with carbidopa to prevent peripheral conversion and reduce side effects. Other medications include dopamine agonists that directly stimulate dopamine receptors, MAO-B inhibitors that prevent dopamine breakdown, and COMT inhibitors that extend levodopa's effect 5.
Some key points to consider in the pharmacological management of Parkinson's disease include:
- The use of levodopa and other dopaminergic drugs, such as dopamine agonists and MAO-B inhibitors, to increase dopamine activity in the brain 4
- The importance of considering patient-specific factors, such as age, disability, and tolerance of drugs, when selecting pharmacotherapy 6
- The potential for motor complications, such as the wearing-off phenomenon and dyskinesias, and the use of adjunct therapies, such as long-acting dopamine agonists and catechol-O-methyltransferase inhibitors, to manage these complications 4
- The role of non-dopaminergic pharmacological approaches, such as zonisamide and istradefylline, in the treatment of Parkinson's disease 4
Overall, the goal of pharmacological therapy in Parkinson's disease is to improve symptoms and quality of life by increasing dopamine activity in the brain, rather than blocking dopamine receptors 5.