Levetiracetam potentiates the antidyskinetic action of amantadine in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of Parkinson’s disease.

M. P. Hill
Journal of Pharmacology and Experimental Therapeutics. 2004-04-02; 310(1): 386-394
DOI: 10.1124/jpet.104.066191

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1. J Pharmacol Exp Ther. 2004 Jul;310(1):386-94. Epub 2004 Mar 5.

Levetiracetam potentiates the antidyskinetic action of amantadine in the
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned primate model of
Parkinson’s disease.

Hill MP(1), Ravenscroft P, Bezard E, Crossman AR, Brotchie JM, Michel A, Grimée
R, Klitgaard H.

Author information:
(1)Motac Neuroscience Ltd, Manchester, United Kingdom.

Levetiracetam (LEV) (Keppra; UCB Pharma, Brussels, Belgium) has recently been
reported to have antidyskinetic activity against levodopa (L-DOPA)-induced
dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned
marmoset and macaque models of Parkinson’s disease. Amantadine is frequently used
as adjunctive therapy for L-DOPA-induced dyskinesia, but adverse effects limit
its clinical utility. The current study was designed to investigate whether LEV
can potentiate the antidyskinetic action of amantadine. The antiparkinsonian and
antidyskinetic effects of LEV (13 and 60 mg/kg) and amantadine (0.01, 0.03, 0.1,
and 0.3 mg/kg), administered alone and in combination, were assessed in the
MPTP-lesioned marmoset model of L-DOPA-induced dyskinesia (n = 12). LEV (60
mg/kg) and amantadine (0.3 mg/kg) administered alone significantly reduced
l-DOPA-induced dyskinesia without compromising the antiparkinsonian action of
l-DOPA. Lower doses were without any significant effects. The combination of LEV
(60 mg/kg) and amantadine (0.01, 0.03, 0.1, and 0.3 mg/kg) significantly
decreased dyskinesia severity, without compromising the antiparkinsonian action
of L-DOPA, more efficaciously than LEV or amantadine monotherapy. These results
support the concept that normalization of different pathophysiological mechanisms
(i.e., altered synchronization between neurons and enhanced N-methyl-D-aspartate
transmission) has a greater efficacy. Combined LEV/amantadine therapy might be
useful as an adjunct to L-DOPA to treat dyskinetic side effects and to expand the
population of Parkinson’s disease patients who benefit from treatment with
amantadine alone.

DOI: 10.1124/jpet.104.066191
PMID: 15004218 [Indexed for MEDLINE]

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