Levodopa infusion does not decrease the onset of abnormal involuntary movements in parkinsonian rats

Authors

  • Maria Papathanou PhD,

    1. Abbott Healthcare Products B.V., Weesp, the Netherlands
    2. Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Science, School of Biomedical Sciences, King's College London, London, United Kingdom
    Current affiliation:
    1. Institute of Cancer Research, Stockholm Branch, Karolinska, Institutet, Sweden
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  • Rika van der Laan,

    1. Abbott Healthcare Products B.V., Weesp, the Netherlands
    Current affiliation:
    1. Vrije Universitat, UPC (Faculteit Aard-en Levenswetenschappen), Amsterdam, The Netherlands
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  • Peter Jenner DSC,

    1. Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Science, School of Biomedical Sciences, King's College London, London, United Kingdom
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  • Sarah Rose PhD,

    1. Neurodegenerative Diseases Research Group, Institute of Pharmaceutical Science, School of Biomedical Sciences, King's College London, London, United Kingdom
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  • Andrew C. McCreary PhD

    1. Abbott Healthcare Products B.V., Weesp, the Netherlands
    Current affiliation:
    1. Brains On-Line, Groningen, The Netherlands
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  • Funding agencies: This work was supported by Abbott Healthcare B.V. (formerly Solvay Pharmaceuticals Laboratories).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Full financial disclosures and author roles may be found in the Acknowledgments section online.

Correspondence to: Dr. Andrew C. McCreary, Brains On-Line, P.O. Box 4030, 9701 EA Groningen, The Netherlands; andymccreary@yahoo.co.uk

Abstract

The short duration of effect of levodopa is linked to pulsatile stimulation of striatal dopamine receptors and dyskinesia induction. However, the recent introduction of intraduodenal (i.d.) infusions and novel oral controlled release formulations of l-dopa may prevent dyskinesia induction and reduce the severity of established involuntary movements. We have compared the effects of twice-daily intraperitoneal (i.p.) administration and daily i.d. infusion of l-dopa on the induction and expression of abnormal involuntary movements in 6-hydroxydopamine (6-OHDA)-lesioned rats. Animals were treated with either twice-daily i.p. administration of l-dopa/carbidopa (7.85/12.5 mg/kg) or an 8-hour i.d. infusion of l-dopa/carbidopa (20/5 mg/mL; infusion rate: 0.04 mL/h) for 14 days, after which treatments were switched between groups and continued for a further 14 days. Pulsatile i.p. administration of l-dopa induced moderate to severe abnormal involuntary movements, which gradually increased in severity over the 14 days, but i.d. infusion of l-dopa induced abnormal involuntary movements of a similar severity. Switching from continuous i.d. to pulsatile i.p. administration of l-dopa continued to provoke severe abnormal involuntary movements expression. Switching from pulsatile i.p. to continuous i.d. l-dopa administration did not alter the peak abnormal involuntary movement severity but tended to reduce their duration. Treatment with less pulsatile l-dopa administration using i.d. infusion does not reduce the risk of the appearance of dyskinesia. By contrast, the duration of established dyskinesia can be reduced by more continuous l-dopa delivery in agreement with clinical experience. © 2012 Movement Disorder Society

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