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The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset.
Eur J Pharmacol. 2010 Jun 10; 635(1-3):109-16.EJ

Abstract

Dopa decarboxylase inhibitors are routinely used to potentiate the effects of L-DOPA in the treatment of Parkinson's disease. However, neither in clinical use nor in experimental models of Parkinson's disease have the timing and dose of dopa decarboxylase inhibitors been thoroughly explored. We now report on the choice of dopa decarboxylase inhibitors, dose and the time of dosing relationships of carbidopa, benserazide and L-alpha-methyl dopa (L-AMD) in potentiating the effects of L-DOPA in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated common marmoset. Pre-treatment with benserazide for up to 3h did not alter the motor response to L-DOPA compared to simultaneous administration with L-DOPA. There was some evidence of a relationship between carbidopa and benserazide dose and increased locomotor activity and the reversal of motor disability. But in general, commonly used dose levels of dopa decarboxylase inhibitors appeared to produce a maximal motor response to L-DOPA. In contrast, dyskinesia intensity and duration continued to increase with both carbidopa and benserazide dose. The novel dopa decarboxylase inhibitor, L-AMD, increased locomotor activity and improved motor disability to the same extent as carbidopa or benserazide but importantly this was accompanied by significantly less dyskinesia. This study shows that currently, dopa decarboxylase inhibitors may be routinely employed in the MPTP-treated primate at doses which are higher than those necessary to produce a maximal potentiation of the anti-parkinsonian effect of L-DOPA. This may lead to excessive expression of dyskinesia in this model of Parkinson's disease and attention should be given to the dose regimens currently employed.

Authors+Show Affiliations

Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College, London, UK.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

20303948

Citation

Tayarani-Binazir, Kayhan A., et al. "The Timing of Administration, Dose Dependence and Efficacy of Dopa Decarboxylase Inhibitors On the Reversal of Motor Disability Produced By L-DOPA in the MPTP-treated Common Marmoset." European Journal of Pharmacology, vol. 635, no. 1-3, 2010, pp. 109-16.
Tayarani-Binazir KA, Jackson MJ, Fisher R, et al. The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset. Eur J Pharmacol. 2010;635(1-3):109-16.
Tayarani-Binazir, K. A., Jackson, M. J., Fisher, R., Zoubiane, G., Rose, S., & Jenner, P. (2010). The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset. European Journal of Pharmacology, 635(1-3), 109-16. https://doi.org/10.1016/j.ejphar.2010.03.006
Tayarani-Binazir KA, et al. The Timing of Administration, Dose Dependence and Efficacy of Dopa Decarboxylase Inhibitors On the Reversal of Motor Disability Produced By L-DOPA in the MPTP-treated Common Marmoset. Eur J Pharmacol. 2010 Jun 10;635(1-3):109-16. PubMed PMID: 20303948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The timing of administration, dose dependence and efficacy of dopa decarboxylase inhibitors on the reversal of motor disability produced by L-DOPA in the MPTP-treated common marmoset. AU - Tayarani-Binazir,Kayhan A, AU - Jackson,Michael J, AU - Fisher,Ria, AU - Zoubiane,Ghada, AU - Rose,Sarah, AU - Jenner,Peter, Y1 - 2010/03/19/ PY - 2009/10/02/received PY - 2010/02/15/revised PY - 2010/03/03/accepted PY - 2010/3/23/entrez PY - 2010/3/23/pubmed PY - 2010/8/18/medline SP - 109 EP - 16 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 635 IS - 1-3 N2 - Dopa decarboxylase inhibitors are routinely used to potentiate the effects of L-DOPA in the treatment of Parkinson's disease. However, neither in clinical use nor in experimental models of Parkinson's disease have the timing and dose of dopa decarboxylase inhibitors been thoroughly explored. We now report on the choice of dopa decarboxylase inhibitors, dose and the time of dosing relationships of carbidopa, benserazide and L-alpha-methyl dopa (L-AMD) in potentiating the effects of L-DOPA in the 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated common marmoset. Pre-treatment with benserazide for up to 3h did not alter the motor response to L-DOPA compared to simultaneous administration with L-DOPA. There was some evidence of a relationship between carbidopa and benserazide dose and increased locomotor activity and the reversal of motor disability. But in general, commonly used dose levels of dopa decarboxylase inhibitors appeared to produce a maximal motor response to L-DOPA. In contrast, dyskinesia intensity and duration continued to increase with both carbidopa and benserazide dose. The novel dopa decarboxylase inhibitor, L-AMD, increased locomotor activity and improved motor disability to the same extent as carbidopa or benserazide but importantly this was accompanied by significantly less dyskinesia. This study shows that currently, dopa decarboxylase inhibitors may be routinely employed in the MPTP-treated primate at doses which are higher than those necessary to produce a maximal potentiation of the anti-parkinsonian effect of L-DOPA. This may lead to excessive expression of dyskinesia in this model of Parkinson's disease and attention should be given to the dose regimens currently employed. SN - 1879-0712 UR - https://www.unboundmedicine.com/medline/citation/20303948/The_timing_of_administration_dose_dependence_and_efficacy_of_dopa_decarboxylase_inhibitors_on_the_reversal_of_motor_disability_produced_by_L_DOPA_in_the_MPTP_treated_common_marmoset_ DB - PRIME DP - Unbound Medicine ER -