Document Detail


D-dopa and L-dopa similarly elevate brain dopamine and produce turning behavior in rats.
MedLine Citation:
PMID:  3129126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the intact rat, intragastric administration of D-dihydroxyphenylalanine (D-DOPA) together with carbidopa (alpha-methyldopa hydrazine, a peripheral dopadecarboxylase inhibitor) increased striatal dopamine concentration to the same extent as a similar treatment with L-DOPA plus carbidopa. In rats with unilateral 6-hydroxydopamine-induced lesions of their substantia nigra, both stereoisomers of DOPA produced significant increases in dopamine and its metabolites in the intact striata. Although dopamine concentrations in the lesioned striata did not change, a significant increase in dopamine metabolites was observed, indicating some extraneuronal formation of dopamine. These results suggest that D-DOPA can be converted to dopamine in the normal striatum as well as in the striatum devoid of dopamine nerve terminals. D- and L-DOPA produced turning behavior in unilaterally lesioned rats with a similar efficacy. The onset of turning after D-DOPA was delayed compared with L-DOPA. Turning behavior elicited by these amino acids was attributed to stimulation of supersensitive dopamine receptors in the lesioned striata by the extraneuronally formed dopamine. Preliminary results suggest that D-DOPA is converted to dopamine via transamination and/or D-amino acid oxidation to 3,4-dihydroxyphenylpyruvic acid which upon further transamination gives rise to L-DOPA and hence dopamine. The relatively fast and slow onset of stimulation of dopamine receptors L-DOPA and D-DOPA respectively suggests that the use of the racemic mixture of DOPA combined with a peripheral dopadecarboxylase inhibitor may prove useful in the treatment of parkinsonism.
Authors:
F Karoum; W J Freed; L W Chuang; E Cannon-Spoor; R J Wyatt; E Costa
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Brain research     Volume:  440     ISSN:  0006-8993     ISO Abbreviation:  Brain Res.     Publication Date:  1988 Feb 
Date Detail:
Created Date:  1988-05-27     Completed Date:  1988-05-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  190-4     Citation Subset:  IM    
Affiliation:
Neuropsychiatry Branch, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, DC 20032.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
Animals
Brain / drug effects,  metabolism*
Carbidopa / pharmacology
Cerebral Ventricles / drug effects,  physiology
Dihydroxyphenylalanine / pharmacology*
Dopamine / metabolism*
Homovanillic Acid / metabolism
Levodopa / pharmacology*
Male
Rats
Rats, Inbred Strains
Stereotyped Behavior / drug effects*
Structure-Activity Relationship
Chemical
Reg. No./Substance:
0/Levodopa; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 38821-49-7/Carbidopa; 63-84-3/Dihydroxyphenylalanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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