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 during the first months to years of therapy may be its long duration of action. This long-duration effect may be due either to a presynaptic storage mechanism or to postsynaptic pharmacodynamic changes. We previously reported that the dopamine agonist ropinirole induced a long-duration response (LDR) in levodopa-naive patients with Parkinson's disease. In this study, we investigated motor responses to the short half-life dopamine agonist lisuride in a group of levodopa naive parkinsonian patients. Once lisuride reached its maximum effect, it was substituted, in randomized order, with placebo. Neither investigators nor patients knew when the active drug was switched to placebo. When patients were switched from lisuride to placebo, their Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and tapping test and 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.
Stocchi
F
F
Dipartimento di Scienze Neurologiche and IRCCS NEUROMED, University of Rome La Sapienza, Italy. fabstocc@tin.it
Vacca
L
L
Berardelli
A
A
De Pandis
F
F
Ruggieri
S
S
D000328:Adult; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D006207:Half-Life; D006801:Humans; D008090:Lisuride / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D013995:Time
D018491:Dopamine Agonists; D008090:Lisuride