Dopamine is a neurotransmitter, or cell signaling molecule, in the central nervous system that is responsible for several important functions, including learning, motor control, emotion, and executive function.
Dopamine exerts its activity in the brain and in other parts of the central nervous system via dopamine receptors ranging from D1 to D5.
Compounds that activate these dopamine receptors are called dopamine receptor agonists.
How do dopamine receptor agonists work in AADC deficiency?
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic disease caused by mutations in the DDC gene. This gene encodes for the AADC enzyme, which plays a role in the production of neurotransmitters such as dopamine and serotonin. The mutations affect the function of the AADC enzyme. As a result, the production of dopamine and serotonin is affected. This leads to symptoms that include muscle spasms, developmental delays, drops in blood pressure, and in some cases, cardiac arrest.
Dopamine receptor agonists are treatments that mimic the action of dopamine by binding to and enhancing the activity of the dopamine receptors in the central nervous system. They help compensate for the reduced dopamine levels, which is a characteristic of AADC deficiency.
What are the dopamine receptor agonists used to treat AADC deficiency?
The consensus guideline for the diagnosis and treatment of AADC deficiency recommends the use of medicines such as pramipexole, ropinirole, rotigotine patch, and bromocriptine as dopamine receptor agonists for first-line treatment of AADC deficiency symptoms.
Pergolide and cabergoline are also dopamine receptor agonists, but they have been withdrawn in many countries due to increased risk of cardiac valvulopathy, or disorders in the valves of the heart. These treatments have a preference for a class of dopamine receptors in the brain called D2-like receptors.
How effective are dopamine receptor agonists in treating AADC deficiency?
While dopamine receptor agonists cannot treat AADC deficiency by themselves, they are used as first-line treatments to reduce the severity of symptoms. They ease symptoms such as hypokinesia, or slowed movements, and chorea, which are involuntary movements. Dystonia, or involuntary muscle contractions, which lead to abnormal postures or repetitive movements, and hypotonia, or low muscle tone, also can be reduced with these medicines.
Research has shown that bromocriptine dosages between 1.25 and 6 mg a day can lead to tangible improvements in AADC deficiency symptoms, whereas in an another case, a dosage above 1.25 mg was not tolerated.
Therefore, the dosage and effectiveness of dopamine receptor agonists can vary between individuals, with some individuals showing no benefits at all.
They can cause several side effects including dizziness, nausea, low blood pressure, anxiety, and depression, and heart damage. Patients undergoing dopamine receptor agonist treatment also are at risk of experiencing dyskinesia, which are unintended and uncontrollable movements, and irritability, or a feeling of frustration or agitation.
Last updated: Sept. 18, 2019
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