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Funded Studies

D3 Receptor Selective Drugs for Parkinson's Dyskinesia

Biomedical research has defined two categories of dopamine receptors, the D1-like (D1 and D5 receptor subtypes) and D2-like (D2, D3 and D4 receptor subtypes) receptors. Despite the similarities in the structure of the D2 and D3 receptors, these two receptors are found in different parts of the brain. Therefore, they are likely doing different jobs in the brain.

Historically it has been difficult to identify drugs that can bind just to the D2 or the D3 dopamine receptor subtypes. A current strategy to prevent or delay the onset of levodopa-induced dyskinesia in early-onset Parkinson's patients is to treat them with drugs characterized as D2-like (D2/D3) dopamine receptor agonists. These drugs interact with both D2 and D3 dopamine receptors in the brain. However, it is unclear whether it is the binding to the D2 receptor or the D3 receptor that is responsible for the therapeutic effects of these drugs. In addition, there is evidence from animal studies suggesting that drugs that bind only to the D3 receptors may alleviate the symptoms of both Parkinson's disease and levodopa-induced dyskinesia.

Our project investigates the possible use of D3 dopamine receptor selective drugs to delay or attenuate levodopa-induced dyskinesia. The goal is to determine if our novel D3 receptor selective compounds attenuate levodopa-induced dyskinesia using a pre-clinical model of human LID. This project brings together research groups with expertise in the areas of medicinal chemistry, molecular pharmacology and neurobiology to precisely define the role of the D2 and D3 dopamine receptors in the development of Parkinson's disease and to identify new drug candidates for the treatment of PD.

Final Outcome

Dr. Luedtke provided evidence suggesting that his novel compounds may have benefit in rodent models of LID. However, some questions remain to be answered in further studies.


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