| 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. | |
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MedLine Citation:
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PMID: 20303948 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Kayhan A Tayarani-Binazir; Michael J Jackson; Ria Fisher; Ghada Zoubiane; Sarah Rose; Peter Jenner |
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Publication Detail:
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Type: Journal Article Date: 2010-03-19 |
Journal Detail:
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Title: European journal of pharmacology Volume: 635 ISSN: 1879-0712 ISO Abbreviation: Eur. J. Pharmacol. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-04-30 Completed Date: 2010-08-17 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1254354 Medline TA: Eur J Pharmacol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 109-16 Citation Subset: IM |
Affiliation:
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Neurodegenerative Diseases Research Centre, School of Health and Biomedical Sciences, King's College, London, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
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pharmacology* Animals Benserazide / administration & dosage, pharmacology Callithrix* Carbidopa / administration & dosage, pharmacology Dopa Decarboxylase / antagonists & inhibitors* Dose-Response Relationship, Drug Drug Administration Schedule Drug Synergism Enzyme Inhibitors / administration & dosage*, pharmacology* Female Levodopa / pharmacology*, therapeutic use Male Methyldopa / administration & dosage, pharmacology Motor Activity / drug effects Movement Disorders / drug therapy*, etiology, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Levodopa; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 322-35-0/Benserazide; 38821-49-7/Carbidopa; 555-30-6/Methyldopa; EC 4.1.1.-/Dopa Decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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