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Central levodopa influx and the clinical motor response to levodopa in patients with Parkinson disease complicated with motor fluctuations and dyskinesias.
Clin Neuropharmacol. 2009 Nov-Dec; 32(6):321-5.CN

Abstract

OBJECTIVE

To study the possible relationship between central levodopa influx and short-term antiparkinsonian and dyskinetic responses to levodopa in patients with Parkinson disease.

METHODS

The clinical response to a single oral dose of standard and controlled-release levodopa/carbidopa was assessed in 12 patients with Parkinson disease complicated with motor fluctuations and dyskinesias. Plasma concentrations of levodopa and large neutral amino acids were determined, and the theoretical central levodopa influx was calculated using a model based on competitive inhibition of substrates to cross the blood-brain barrier.

RESULTS

The mean (SD) central levodopa influxes at the onset of the antiparkinsonian clinical effect were 19.7 (10.9 x 10(-3) and 19.1 (7.4 x 10(-3) nmol min(-1) g(-)1 (P >0.1) for standard and controlled-release levodopa, respectively. The mean (SD) central levodopa influxes at the onset of choreic dyskinesias were 20.1 (8.2 x 10 (-3) and 19.9 (10.8 x 10(-3) nmol min (-1) g(-)1 (P 9 0.1) for standard and controlled-release levodopa, respectively. During the tests, choreic dyskinesias were associated with a central levodopa influx of 10 x 10(-3) nmol min(-1) g(-1) or greater, and foot dystonia occurred with a central levodopa influx less than 9 x 10(-3) nmol min(-1) g(-1).

CONCLUSIONS

The clinical response to levodopa in patients with advanced Parkinson disease may be related to central levodopa influx. We found no differences in the central levodopa influx threshold for clinical improvement with different levodopa formulations. The central levodopa influxes at the onset of choreic dyskinesias and antiparkinsonian effect were similar. Choreic dyskinesias and foot dystonia were associated with high and low central levodopa influx, respectively.

Authors+Show Affiliations

Movement Disorders Research Unit, Hospital Universitario Gregorio Marañón, c/ Doctor Esquerdo 46, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

19667975

Citation

López-Ariztegui, Nuria, et al. "Central Levodopa Influx and the Clinical Motor Response to Levodopa in Patients With Parkinson Disease Complicated With Motor Fluctuations and Dyskinesias." Clinical Neuropharmacology, vol. 32, no. 6, 2009, pp. 321-5.
López-Ariztegui N, Arévalo MA, de Ceballos ML, et al. Central levodopa influx and the clinical motor response to levodopa in patients with Parkinson disease complicated with motor fluctuations and dyskinesias. Clin Neuropharmacol. 2009;32(6):321-5.
López-Ariztegui, N., Arévalo, M. A., de Ceballos, M. L., & Grandas, F. (2009). Central levodopa influx and the clinical motor response to levodopa in patients with Parkinson disease complicated with motor fluctuations and dyskinesias. Clinical Neuropharmacology, 32(6), 321-5. https://doi.org/10.1097/WNF.0b013e3181b40378
López-Ariztegui N, et al. Central Levodopa Influx and the Clinical Motor Response to Levodopa in Patients With Parkinson Disease Complicated With Motor Fluctuations and Dyskinesias. Clin Neuropharmacol. 2009 Nov-Dec;32(6):321-5. PubMed PMID: 19667975.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Central levodopa influx and the clinical motor response to levodopa in patients with Parkinson disease complicated with motor fluctuations and dyskinesias. AU - López-Ariztegui,Nuria, AU - Arévalo,Maria Angeles, AU - de Ceballos,Maria L, AU - Grandas,Francisco, PY - 2009/8/12/entrez PY - 2009/8/12/pubmed PY - 2010/2/26/medline SP - 321 EP - 5 JF - Clinical neuropharmacology JO - Clin Neuropharmacol VL - 32 IS - 6 N2 - OBJECTIVE: To study the possible relationship between central levodopa influx and short-term antiparkinsonian and dyskinetic responses to levodopa in patients with Parkinson disease. METHODS: The clinical response to a single oral dose of standard and controlled-release levodopa/carbidopa was assessed in 12 patients with Parkinson disease complicated with motor fluctuations and dyskinesias. Plasma concentrations of levodopa and large neutral amino acids were determined, and the theoretical central levodopa influx was calculated using a model based on competitive inhibition of substrates to cross the blood-brain barrier. RESULTS: The mean (SD) central levodopa influxes at the onset of the antiparkinsonian clinical effect were 19.7 (10.9 x 10(-3) and 19.1 (7.4 x 10(-3) nmol min(-1) g(-)1 (P >0.1) for standard and controlled-release levodopa, respectively. The mean (SD) central levodopa influxes at the onset of choreic dyskinesias were 20.1 (8.2 x 10 (-3) and 19.9 (10.8 x 10(-3) nmol min (-1) g(-)1 (P 9 0.1) for standard and controlled-release levodopa, respectively. During the tests, choreic dyskinesias were associated with a central levodopa influx of 10 x 10(-3) nmol min(-1) g(-1) or greater, and foot dystonia occurred with a central levodopa influx less than 9 x 10(-3) nmol min(-1) g(-1). CONCLUSIONS: The clinical response to levodopa in patients with advanced Parkinson disease may be related to central levodopa influx. We found no differences in the central levodopa influx threshold for clinical improvement with different levodopa formulations. The central levodopa influxes at the onset of choreic dyskinesias and antiparkinsonian effect were similar. Choreic dyskinesias and foot dystonia were associated with high and low central levodopa influx, respectively. SN - 1537-162X UR - https://www.unboundmedicine.com/medline/citation/19667975/Central_levodopa_influx_and_the_clinical_motor_response_to_levodopa_in_patients_with_Parkinson_disease_complicated_with_motor_fluctuations_and_dyskinesias_ L2 - https://doi.org/10.1097/WNF.0b013e3181b40378 DB - PRIME DP - Unbound Medicine ER -