Clinical neuropharmacology · 2004
Levetiracetam Interferes With the L-dopa priming process in MPTP-lesioned drug-naive marmosets.
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Hill Michael P, Brotchie Jonathan M, Crossman Alan R, Bezard Erwan, Michel Anne, Grimée Renee, Klitgaard Henrik
Аннотация
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.
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.