Document Detail


Time-related changes in serum perphenazine, striatal 3H-spiperone binding and regional brain acid metabolites of dopamine and 5-hydroxy-tryptamine after a single dose of perphenazine.
MedLine Citation:
PMID:  1693589     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A single dose of perphenazine (5.0 mg/kg) was administered intraperitoneally to male Wistar rats. The time-related alterations in serum levels of perphenazine, striatal 3H-spiperone binding ex vivo and the regional brain metabolism of dopamine and 5-hydroxy-tryptamine were studied. Low serum levels of perphenazine were observed together with increased Kd of 3H-spiperone. No significant changes in Bmax were observed. Since Kd of 3H-spiperone binding peaked several hours after the maximal serum levels of perphenazine, perphenazine in serum appeared not to directly reflect the events at the receptor level. The concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy, 4-hydroxyphenylacetic acid (HVA) in the striatum were increased after perphenazine. They were maximal 1-3 h after the drug administration and showed positive correlations (correlation coefficient 0.93 and 0.80, respectively) with the serum levels of perphenazine. Increased levels of HVA were also observed both in the olfactory tubercle and in the frontal cortex. However, in the olfactory tubercle, administration of perphenazine did not significantly increase the DOPAC concentrations. In the olfactory tubercle 5-hydroxyindoleacetic acid (5-HIAA) was decreased 1-24 h after administration of perphenazine. In the striatum and in the frontal cortex only slight changes in 5-HIAA were seen. Thus, in the olfactory tubercle 5-hydroxytryptaminergic mechanisms could modulate the dopaminergic neurotransmission.
Authors:
T Mjörndal; S A Persson
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Fundamental & clinical pharmacology     Volume:  4     ISSN:  0767-3981     ISO Abbreviation:  Fundam Clin Pharmacol     Publication Date:  1990  
Date Detail:
Created Date:  1990-07-16     Completed Date:  1990-07-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8710411     Medline TA:  Fundam Clin Pharmacol     Country:  FRANCE    
Other Details:
Languages:  eng     Pagination:  213-22     Citation Subset:  IM    
Affiliation:
Department of Pharmacology, University of Umeå, Sweden.
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MeSH Terms
Descriptor/Qualifier:
3,4-Dihydroxyphenylacetic Acid / metabolism
5-Hydroxytryptophan / metabolism*
Animals
Brain / drug effects,  metabolism
Brain Chemistry / drug effects*
Corpus Striatum / drug effects,  metabolism*
Dopamine / metabolism*
Homovanillic Acid / metabolism
Hydroxyindoleacetic Acid / metabolism
Male
Perphenazine / pharmacology*
Rats
Rats, Inbred Strains
Receptors, Dopamine / drug effects
Spiperone / metabolism*
Stereoisomerism
Chemical
Reg. No./Substance:
0/Receptors, Dopamine; 102-32-9/3,4-Dihydroxyphenylacetic Acid; 306-08-1/Homovanillic Acid; 54-16-0/Hydroxyindoleacetic Acid; 56-69-9/5-Hydroxytryptophan; 58-39-9/Perphenazine; 749-02-0/Spiperone

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


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