Levetiracetam interferes with the L-dopa priming process in MPTP-lesioned drug-naive marmosets

Objective: Levetiracetam (LEV; Keppra, UCB Pharma) has been shown to reduce established L-3,4 dihydroxyphenylalanine (L-dopa)-induced dyskinesia. This study investigated whether LEV can modify induction of dyskinesia by L-dopa or the process of priming. Methods: Drug-naive MPTP (1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine) -lesioned marmosets were treated for 21 days with L-dopa/LEV or L-dopa alone. Subsequently, the animals were left untreated for 1 week and then both groups were challenged with a single dose of L-dopa alone on day 29. Behavior was assessed by automated activity counts and by post hoc analysis of videotapes using validated rating scales. Results: LEV had no significant effect on the appearance of dyskinesia when administered de novo in combination with L-dopa. However, after a week of drug holiday, the 2 groups exhibited a different response to an acute L-dopa challenge. Thus, animals previously treated with L-dopa alone exhibited a similar level of dyskinesia to that seen on day 21 of the repeated treatment phase of the study. However, animals previously treated with L-dopa/LEV demonstrated significantly reduced dyskinesia compared with day 21 of the repeated treatment phase of the study. Conclusions: LEV does not modify the onset of dyskinesia following de novo treatment with L-dopa. However, concomitant treatment with L-dopa/LEV reduces the level of dyskinesia induced by L-dopa following a drug holiday. Thus, prior treatment with LEV appears to modify the mechanisms responsible for the maintenance of L-dopa-induced dyskinesia.