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Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II.
Ann Neurol. 1988 Sep; 24(3):372-8.AN

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 antiparkinsonian and dyskinetic effects suggest involvement of separate 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 the motor fluctuations, especially of the on-off type, which complicate levodopa therapy of patients with advanced Parkinson's disease.

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)

Journal Article

Language

eng

PubMed ID

3228271

Citation

Mouradian, M M., et al. "Motor Fluctuations in Parkinson's Disease: Central Pathophysiological Mechanisms, Part II." Annals of Neurology, vol. 24, no. 3, 1988, pp. 372-8.
Mouradian MM, Juncos JL, Fabbrini G, et al. Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II. Ann Neurol. 1988;24(3):372-8.
Mouradian, M. M., Juncos, J. L., Fabbrini, G., Schlegel, J., Bartko, J. J., & Chase, T. N. (1988). Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II. Annals of Neurology, 24(3), 372-8.
Mouradian MM, et al. Motor Fluctuations in Parkinson's Disease: Central Pathophysiological Mechanisms, Part II. Ann Neurol. 1988;24(3):372-8. PubMed PMID: 3228271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Motor fluctuations in Parkinson's disease: central pathophysiological mechanisms, Part II. AU - Mouradian,M M, AU - Juncos,J L, AU - Fabbrini,G, AU - Schlegel,J, AU - Bartko,J J, AU - Chase,T N, PY - 1988/9/1/pubmed PY - 1988/9/1/medline PY - 1988/9/1/entrez SP - 372 EP - 8 JF - Annals of neurology JO - Ann Neurol VL - 24 IS - 3 N2 - 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 antiparkinsonian and dyskinetic effects suggest involvement of separate 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 the motor fluctuations, especially of the on-off type, which complicate levodopa therapy of patients with advanced Parkinson's disease. SN - 0364-5134 UR - https://www.unboundmedicine.com/medline/citation/3228271/Motor_fluctuations_in_Parkinson's_disease:_central_pathophysiological_mechanisms_Part_II_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0364-5134&date=1988&volume=24&issue=3&spage=372 DB - PRIME DP - Unbound Medicine ER -