Levodopa consumption reduces dopaminergic receptor responsiveness in Parkinson's disease

In seven patients with Parkinson's disease with daily motor fluctuations, we found that the same subcutaneous apomorphine dose that improved motor function when given in the morning after a normal night without taking levodopa failed to turn patients "on" during afternoon and evening "off" periods, and on a different morning after receiving levodopa during the night. No significant changes in levodopa or 3-O-methyldopa plasma levels that could explain these variations were detected. These findings suggest that increased daily levodopa consumption may reduce striatal responsiveness to dopaminergic stimulation.