Long-duration effect and the postsynaptic compartment: Study using a dopamine agonist with a short half-life

A possible reason why levodopa induces a sustained, stable motor benefit du ring the first months to years of therapy may be its long duration of actio n. This lone-duration effect may be due either to a presynaptic storage mec hanism or to postsynaptic pharmacodynamic changes. We previously reported t hat the dopamine agonist ropinirole induced a long-duration response (LDR) in levodopa-naive patients with Parkinson's disease. In this study, we inve stigated motor responses to the short half-life dopamine agonist lisuride i n a group of levodopa naive parkinsonian patients. Once lisuride reached it s maximum effect, it was substituted, in randomized order, with placebo. Ne ither investigators nor patients knew when the active drug was switched to placebo. When patients were switched from lisuride to placebo, their Unifie d Parkinson's Disease Rating Scale (UPDRS) motor scores and tapping test an d screw scores declined to baseline values within a mean 9.0 +/- 1.9 days. The results confirmed that, like ropinirole and levodopa, the short-acting dopamine agonist lisuride induces a long-duration response, probably due to postsynaptic changes. (C) 2001 Movement Disorder Society.