Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II

Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II The contribution of central pharmacodynamic mechanisms to the pathogenesis of motor fluctuations in advanced Parkinson's disease was studied in 29 patients by evaluating their acute response to intravenously injected. levodopa. While the threshold dose for an antiparkinsonian effect did not change, that for induction of dyskinesia showed a progressive reduction in 4 groups: (1) levodopa‐naive patients, (2) those with a stable response to oral administration, and (3) those with wearing‐off or (4) on‐off fluctuations. Concomitantly, the therapeutic window for levodopa narrowed and the levodopa dose—antiparkinsonian response slope increased. The antiparkinsonian threshold dose correlated best with duration of symptoms; the dyskinesia threshold dose, therapeutic window, and dose‐response slope related most closely with the duration of levodopa treatment. The differing dose‐response profiles for the antiparkinosonian and dyskinetic effects suggest involvement of Septemberarate pharmacological mechanisms. The present results, taken together with previous observations that the wearing‐off phenomenon responds promptly to plasma levodopa stabilization while on‐off fluctuations tend to diminish over several days, suggest that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and motor fluctuations, especially of the on‐off type, which complicate levodopa therapy of patients with advance Parkinson's disease. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Neurology Wiley

Motor fluctuations in Parkinson's disease: Central pathophysiological mechanisms, part II

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Publisher
Wiley
Copyright
Copyright © 1988 American Neurological Association
ISSN
0364-5134
eISSN
1531-8249
D.O.I.
10.1002/ana.410240304
Publisher site
See Article on Publisher Site

Abstract

The contribution of central pharmacodynamic mechanisms to the pathogenesis of motor fluctuations in advanced Parkinson's disease was studied in 29 patients by evaluating their acute response to intravenously injected. levodopa. While the threshold dose for an antiparkinsonian effect did not change, that for induction of dyskinesia showed a progressive reduction in 4 groups: (1) levodopa‐naive patients, (2) those with a stable response to oral administration, and (3) those with wearing‐off or (4) on‐off fluctuations. Concomitantly, the therapeutic window for levodopa narrowed and the levodopa dose—antiparkinsonian response slope increased. The antiparkinsonian threshold dose correlated best with duration of symptoms; the dyskinesia threshold dose, therapeutic window, and dose‐response slope related most closely with the duration of levodopa treatment. The differing dose‐response profiles for the antiparkinosonian and dyskinetic effects suggest involvement of Septemberarate pharmacological mechanisms. The present results, taken together with previous observations that the wearing‐off phenomenon responds promptly to plasma levodopa stabilization while on‐off fluctuations tend to diminish over several days, suggest that postsynaptic modifications, presumably at the receptor level, serve as the major determinant for the increasing difficulty with optimal dose adjustment and motor fluctuations, especially of the on‐off type, which complicate levodopa therapy of patients with advance Parkinson's disease.

Journal

Annals of NeurologyWiley

Published: Sep 1, 1988

References

  • Levodopa pharmacokinetic mechanisms and motor fluctuations in Parkinson's disease
    Fabbrini, Fabbrini; Juncos, Juncos; Mouradian, Mouradian
  • Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, part I
    Fabbrini, Fabbrini; Mouradian, Mouradian; Juncos, Juncos
  • Motor fluctuations in Parkinson's disease: pathogenetic and therapeutic studies
    Mouradian, Mouradian; Juncos, Juncos; Fabbrini, Fabbrini; Chase, Chase
  • Changes in neostriatal dopamine concentrations in response to levodopa infusions
    Doller, Doller; Connor, Connor
  • Levodopa‐induced dopamine receptor hypersensitivity
    Klawans, Klawans; Goetz, Goetz; Nausieda, Nausieda; Weiner, Weiner
  • Long‐term L‐dopa pretreatment of mice: central receptor subsensitivity or supersensitivity
    Bailey, Bailey; Jackson, Jackson; Bracs, Bracs
  • Intravenous lisuride corrects oscillations of motor performance in Parkinson's disease
    Obeso, Obeso; Luquin, Luquin; Martinez Lage, Martinez Lage

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