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Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I.
Ann Neurol. 1988 Sep; 24(3):366-71.AN

Abstract

The duration of the antiparkinsonian action of levodopa was studied in 48 patients with various response patterns to the oral administration of the dopamine precursor. Deterioration in motor scores after abrupt cessation of a steady-state intravenous levodopa infusion occurred at two successive rates: an initial rapid phase followed by a terminal slower phase. Efficacy half-time decreased and initial efficacy decay slope increased with progression of levodopa response groups from never treated to stable responders, and then to fluctuating responders of the wearing-off type and finally of the on-off type. Efficacy half-time exceeded plasma levodopa half-life in the 2 nonfluctuating groups, approximated it in those patients with wearing-off responses, and was significantly shorter in patients with fluctuations of the on-off type. The half-times for the decline in antiparkinsonian efficacy and dyskinesia severity differed significantly, suggesting different pharmacological mechanisms. Motor fluctuation severity correlated best with initial efficacy decay slope, and both were best predicted by parkinsonian symptom severity. The dyskinesia decay rate correlated most closely with levodopa dose. These results support the view that progressive dopamine neuron degeneration reduces the brain's ability to buffer shifts in levodopa availability attending its periodic oral administration; the clinical result is wearing-off phenomenon. The on-off phenomenon as well as dyskinesia apparently reflects additional secondary changes related to levodopa therapy and occurring postsynaptically.

Authors+Show Affiliations

Experimental Therapeutics Branch, National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, MD 20892.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

3228270

Citation

Fabbrini, G, et al. "Motor Fluctuations in Parkinson's Disease: Central Pathophysiological Mechanisms, Part I." Annals of Neurology, vol. 24, no. 3, 1988, pp. 366-71.
Fabbrini G, Mouradian MM, Juncos JL, et al. Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I. Ann Neurol. 1988;24(3):366-71.
Fabbrini, G., Mouradian, M. M., Juncos, J. L., Schlegel, J., Mohr, E., & Chase, T. N. (1988). Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I. Annals of Neurology, 24(3), 366-71.
Fabbrini G, et al. Motor Fluctuations in Parkinson's Disease: Central Pathophysiological Mechanisms, Part I. Ann Neurol. 1988;24(3):366-71. PubMed PMID: 3228270.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part I. AU - Fabbrini,G, AU - Mouradian,M M, AU - Juncos,J L, AU - Schlegel,J, AU - Mohr,E, AU - Chase,T N, PY - 1988/9/1/pubmed PY - 1988/9/1/medline PY - 1988/9/1/entrez SP - 366 EP - 71 JF - Annals of neurology JO - Ann Neurol VL - 24 IS - 3 N2 - The duration of the antiparkinsonian action of levodopa was studied in 48 patients with various response patterns to the oral administration of the dopamine precursor. Deterioration in motor scores after abrupt cessation of a steady-state intravenous levodopa infusion occurred at two successive rates: an initial rapid phase followed by a terminal slower phase. Efficacy half-time decreased and initial efficacy decay slope increased with progression of levodopa response groups from never treated to stable responders, and then to fluctuating responders of the wearing-off type and finally of the on-off type. Efficacy half-time exceeded plasma levodopa half-life in the 2 nonfluctuating groups, approximated it in those patients with wearing-off responses, and was significantly shorter in patients with fluctuations of the on-off type. The half-times for the decline in antiparkinsonian efficacy and dyskinesia severity differed significantly, suggesting different pharmacological mechanisms. Motor fluctuation severity correlated best with initial efficacy decay slope, and both were best predicted by parkinsonian symptom severity. The dyskinesia decay rate correlated most closely with levodopa dose. These results support the view that progressive dopamine neuron degeneration reduces the brain's ability to buffer shifts in levodopa availability attending its periodic oral administration; the clinical result is wearing-off phenomenon. The on-off phenomenon as well as dyskinesia apparently reflects additional secondary changes related to levodopa therapy and occurring postsynaptically. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/3228270/Motor_fluctuations_in_Parkinson's_disease:_central_pathophysiological_mechanisms_Part_I_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1988&volume=24&issue=3&spage=366 DB - PRIME DP - Unbound Medicine ER -