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.
Hill
Michael P
MP
Motac Neuroscience, Ltd., Manchester, UK.
Brotchie
Jonathan M
JM
Crossman
Alan R
AR
Bezard
Erwan
E
Michel
Anne
A
Grimée
Renee
R
Klitgaard
Henrik
H
D000704:Analysis of Variance; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D000978:Antiparkinson Agents / Q000037:antagonists & inhibitors; D002144:Callithrix; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D020820:Dyskinesias / Q000188:drug therapy*; D000077287:Levetiracetam; D007980:Levodopa / Q000037:antagonists & inhibitors*; D020267:MPTP Poisoning / Q000188:drug therapy*; D010889:Piracetam / Q000031:analogs & derivatives / Q000627:therapeutic use*; D011897:Random Allocation; D013997:Time Factors
D000927:Anticonvulsants; D000978:Antiparkinson Agents; D000077287:Levetiracetam; D007980:Levodopa; D010889:Piracetam