THE LONG-DURATION ACTION OF LEVODOPA MAY BE DUE TO A POSTSYNAPTIC EFFECT

A single dose of levodopa (L-DOPA) reduces motor disability in Parkins on's disease (PD) for a few hours, a short-duration effect. However, t here are suggestions that L-DOPA may also produce a long-duration bene fit of some days. In the present study, we examined the long-duration action of L-DOPA by observing the time taken to achieve maximum stable benefit after starting a constant dose of sinemet-CR (sinemet-CR) (20 0 g L-DOPA/50 mg carbidopa) twice daily in nine newly diagnosed patien ts, and the time taken to deteriorate back to baseline after stopping treatment. A single dose of sinemet-CR (200 rug L-DOPA/50 mg carbidopa ) had little obvious short-duration action on the Unified PD Rating Sc ale (UPDRS) motor scores in the majority of patients, either before st arting chronic sinemet-CR therapy (200 mg L-DOPA/50 mg carbidopa, b,i. d,) or after chronic treatment, However, all patients gradually improv ed on chronic sinemet-CR therapy, laking 9.3 +/- 1.8 days to achieve m aximum response, On stopping chronic sinemet-CR treatment, it took 6.8 +/- 3.0 days for the same patients to deteriorate back to baseline mo tor disability. In similar experiments, the time taken to deteriorate back to baseline after stopping treatment with the directly acting dop amine agonist ropinirole (9-21 mg daily) in eight other de novo patien ts with PD was found to be 6.2 +/- 1.7 days. The long-duration effect of L-DOPA and ropinirole may, therefore, be due to some slowly evolvin g postsynaptic pharmacodynamic change in the central nervous system (C NS). Loss of this long-duration action may be responsible for the emer gence of motor fluctuations an chronic L-DOPA therapy.