Effect of the D3 dopamine receptor partial agonist BP897 [N-[4-(4-(2-methoxyphenyl)piperazinyl)butyl]-2-naphthamide] on L-3,4-dihydroxyphenylalanine-induced dyskinesias and parkinsonism in squirrel monkeys

The Journal of Pharmacology and Experimental Therapeutics
Albert HsuM Quik

Abstract

Although l-3,4-dihydroxyphenylalanine (L-dopa) is one of the most effective therapies for Parkinson's disease, continued treatment may result in excessive involuntary movements known as L-dopa-induced dyskinesias (LIDs). Because LIDs can become dose-limiting, there is great interest in finding ways to ameliorate or prevent this troubling side effect of L-dopa therapy. It was recently reported that the D3 receptor partial agonist BP897 [N-[4-(4-(2-methoxyphenyl)piperazinyl)butyl]-2-naphthamide] reduces LIDs without diminishing antiparkinsonian effects of L-dopa in macaques. In the present study, we tested the effects of BP897 on LIDs in squirrel monkeys, a nonhuman primate particularly prone to dyskinesias. Parkinsonism was induced using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Animals were then gavaged with L-dopa/carbidopa (7.5 or 15 mg/kg/dose) without and with BP897. The effects of BP897 treatment were evaluated on several components of LIDs, including time course, peak dyskinesias, and area under the curve (AUC), a measure that encompasses both peak and duration of the response. Analyses of the time course and overall dyskinetic response (AUC) showed that BP897 significantly reduced LIDs but at the expense of the antip...Continue Reading

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Citations

Mar 7, 2012·Cold Spring Harbor Perspectives in Medicine·Gregory PorrasErwan Bezard
Mar 5, 2010·The Journal of Pharmacology and Experimental Therapeutics·Tanuja BordiaMaryka Quik
May 11, 2005·Expert Opinion on Investigational Drugs·Spiros Konitsiotis
Oct 26, 2007·Annals of Neurology·Maryka QuikDonato Di Monte
May 20, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Souha MahmoudiPierre J Blanchet
Jul 22, 2014·Movement Disorders : Official Journal of the Movement Disorder Society·Peter Jenner
Jul 12, 2005·Neurobiology of Disease·Maya G PurisaiDonato A Di Monte
Jul 26, 2015·Progress in Neurobiology·Matthieu F BastideErwan Bézard
Jul 5, 2005·Drug Discovery Today·Jeffrey N Joyce, Mark J Millan
Oct 3, 2006·Movement Disorders : Official Journal of the Movement Disorder Society·Laura Silveira-MoriyamaAndrew J Lees
Mar 11, 2018·The Journal of Pharmacology and Experimental Therapeutics·Nicolas VeyresPhilippe Huot
Jan 16, 2013·Pharmacological Reviews·Philippe HuotJonathan M Brotchie
May 6, 2020·Expert Opinion on Emerging Drugs·Sohaila AlShimemeriNaomi P Visanji
Apr 4, 2021·Biomedicines·Kathryn Lanza, Christopher Bishop

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