Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID: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. 1500 18

We evaluated the tolerability and preliminary efficacy of levetiracetam (LEV; Keppra) in reducing levodopa-induced dyskinesias in Parkinson's disease (PD) in an open-label pilot study. Nine PD patients who were experiencing peak-dose dyskinesias for at least 25% of the awake day and were at least moderately disabling were treated with LEV in doses up to 3,000 mg for up to 60 days. The primary outcome measure was the percent of the awake day that patients spent on without dyskinesia or with nontroublesome dyskinesia (good on time). The mean dose of LEV at endpoint was 625+/-277 mg/day. LEV significantly improved percent of the awake day on without dyskinesia or with nontroublesome dyskinesia at endpoint compared to baseline (43% +/- 12% vs. 61% +/- 17%; P=0.02). Percent on time with troublesome dyskinesia decreased from 23% +/- 10% at baseline to 11% +/- 6% at endpoint, although not significantly. There was no significant increase in off time from baseline to endpoint. There was a 56% dropout rate, mostly due to somnolence. In PD patients who experienced peak-dose dyskinesia for at least 25% of the awake day, LEV significantly improved on time without dyskinesia or with nontroublesome dyskinesia.
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PMID:Open-label pilot study of levetiracetam (Keppra) for the treatment of levodopa-induced dyskinesias in Parkinson's disease. 1595 35