CLINICAL IMPLICATIONS OF SUSTAINED DOPAMINERGIC STIMULATION

Fluctuations in motor performance are the major problems in chronic ma nagement of Parkinson's disease. Most of these fluctuations reflect th e decline of levodopa availability. As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic dopamine receptors at this point are exposed to a no nphysiologic shift in dopamine level, which may induce changes at the receptor site and contribute to the appearance of ''on-off'' phenomena and dyskinesias. We compared a group of 18 patients treated for 60 co nsecutive months with continuous subcutaneous lisuride infusion with a group of 20 patients treated with conventional oral levodopa treatmen t. The clinical evaluations performed during the study showed in the l isuride group only a worsening of dyskinesias, whereas the other sympt oms remained unchanged. In the other group the evaluation scores showe d a significant worsening of all long-term treatment complications. Th e slow-release preparations of levodopa may ensure a more continuous d opaminergic stimulation than standard formulations. However, the use o f these compounds is difficult in severely fluctuating patients becaus e the lack of a plasma peak level usually leads to a very long delay b efore patients turn ''on.'' We studied the pharmacokinetic and clinica l effects of the two slow-release preparations of levodopa [Madopar HB S and Sinemet controlled-release (CR)] and a combination of Sinemet CR plus standard Sinemet in 13 fluctuating parkinsonian patients. The re sults of this study show that the combination of standard Sinemet and Sinemet CR ensures a more prolonged clinical effect with a very short latency to the ''on'' phase.