Related Experiment Videos
3-O-methyldopa administration does not alter fluorodopa transport into the brain
M Guttman1, G Léger, J M Cedarbaum
1Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Annals of Neurology
|June 1, 1992
Summary
3-O-methyldopa (3OMD) does not inhibit the brain transport of 6-[18F]fluorodopa (6-FD) at typical L-dopa therapy concentrations. This finding suggests 3OMD is not responsible for the declining therapeutic response in advanced Parkinson's disease patients.
Area of Science:
- Neuroscience
- Pharmacology
- Radiochemistry
Background:
- L-dopa is a primary treatment for Parkinson's disease.
- A declining therapeutic response is observed in advanced Parkinson's disease.
- 3-O-methyldopa (3OMD) is a metabolite of L-dopa that accumulates during therapy.
Purpose of the Study:
- To investigate if 3-O-methyldopa (3OMD) inhibits the brain uptake of 6-[18F]fluorodopa (6-FD).
- To determine the role of 3OMD in the reduced efficacy of L-dopa in advanced Parkinson's disease.
Main Methods:
- Positron emission tomography (PET) studies were conducted in cynomolgus monkeys.
- 6-[18F]fluorodopa (6-FD) brain transport was measured with and without 3OMD infusion.
- 3OMD plasma concentrations mimicked those in patients undergoing chronic L-dopa therapy.
Main Results:
- Elevated plasma 3OMD levels (39 +/- 4 microM) did not affect the blood-brain transfer rate of 6-FD.
- The brain uptake of 6-FD remained unchanged in the presence of 3OMD.
Conclusions:
- 3-O-methyldopa (3OMD) does not significantly inhibit 6-[18F]fluorodopa (6-FD) brain transport at therapeutic concentrations.
- The presence of 3OMD in parkinsonian patients on L-dopa therapy is unlikely to alter 6-FD PET study results.
- These findings do not support the hypothesis that 3OMD-induced inhibition of L-dopa brain transport causes the declining response in advanced Parkinson's disease.