Document Detail


Behavioral and radioligand binding evidence for irreversible dopamine receptor blockade by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline.
MedLine Citation:
PMID:  6133202     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible alpha adrenergic antagonist, also acts as a potent and longlasting in vivo antagonist of D-2 dopamine receptors. Rats given EEDQ 3-10 mg/kg i.p. exhibit catalepsy and greatly reduced apomorphine-induced stereotypy, behavioral effects associated with D-2 dopamine receptor blockade. These effects are apparent up to 4 days after drug administration, with scores returning to control level by day 7. In vitro receptor binding assays of striatal membrane preparations from these animals using the radioligand 3H-spiroperidol directly demonstrate that EEDQ is a potent D-2 dopamine receptor antagonist, revealing the apparent basis of the behavioral effects of EEDQ. This antagonism proceeds via a reduction in D-2 receptor Bmax, with no change in the observed KD for 3H-spiroperidol, and is resistant to extensive washing of the membrane preparation after in vivo EEDQ exposure. These observations suggest that EEDQ inhibition of D-2 receptors is irreversible. Administration of behaviorally active doses of EEDQ effect a reduction of 50-85% in D-2 receptor number. Recovery of this loss roughly parallels recovery of normal catalepsy and apomorphine stereotypy scores. These doses of EEDQ also reduce binding of 3H-flupentixol to D-1 and 3H-dopamine to D-3 type dopaminergic binding sites, putative dopamine receptors with no known behavioral correlates. Recovery of D-1 and D-3 binding also occurs with a similar timecourse. Because of the apparent covalent nature of its interaction with dopamine receptors and because of its activity after peripheral administration, EEDQ may prove useful in the study of the function and turnover of dopamine receptors.
Authors:
M W Hamblin; I Creese
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Life sciences     Volume:  32     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  1983 May 
Date Detail:
Created Date:  1983-06-23     Completed Date:  1983-06-23     Revised Date:  2011-12-06    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  2247-55     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Antagonists / pharmacology*
Animals
Apomorphine / pharmacology
Catalepsy / chemically induced*
Dose-Response Relationship, Drug
Humans
Injections, Intraperitoneal
Male
Quinolines / administration & dosage,  pharmacology*
Rats
Receptors, Dopamine / drug effects*
Spiperone / metabolism
Stereotyped Behavior / drug effects*
Time Factors
Grant Support
ID/Acronym/Agency:
BM07198/BM/FDA HHS; MH00316/MH/NIMH NIH HHS; MH32990/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Quinolines; 0/Receptors, Dopamine; 16357-59-8/EEDQ; 58-00-4/Apomorphine; 749-02-0/Spiperone

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


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