Document Detail


Antimuscarinic action of an alkane-bis-ammonium compound alone and in combination with (+)-benzetimide.
MedLine Citation:
PMID:  1242377     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heptane-1,7-bis-(dimethyl-3'-phthalimidopropylammonium bromide) ('C7/3-phthalimido-propyl') in concentrations of 10(-7) to 0.5 X 10(-3) inhibited negative inotropic responses to carbachol or acetylcholine to a similar extent in the electrically stimulated isolated guinea-pig left atrium. However, the degree of antagonism of responses to carbachol was less than expected for a competitive antagonist when the higher concentrations of 'C7/3-phthalimido-propyl' were employed. When 'C7/3-phthalimido-propyl' was combined with competitive antagonists such as (+)-benzetimide, atropine or homatropine the degree of antagonism was greater than expected for combination of 2 competitive antagonists. Qualitatively similar results were obtained in the presence of practolol (1.5 X 10(-5) M). The results obtained with 'C7/3-phthalimido-propyl' are shown to agree with theoretical predictions for a metaffinoid antagonist which influences the affinities of both agonists and competitive antagonists by combining with a regulatory site distinct from, but interdependent with the binding sites for agonists and competitive antagonists. Further, it is shown that the alkane-bis-ammonium compound produces a much greater reduction in the affinity of carbachol than that of the competitive antagonists and as a consequence causes 'supra-additive' effects when combined with a competitive antagonist. The reduction in the affinity of (+)-benzetimide produced by 'C7/3-phthalimido-propyl' did not differ significantly from the reduction in the affinities of atropine or homatropine.
Authors:
F Mitchelson
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  European journal of pharmacology     Volume:  33     ISSN:  0014-2999     ISO Abbreviation:  Eur. J. Pharmacol.     Publication Date:    1975 Sep-Oct
Date Detail:
Created Date:  1976-01-26     Completed Date:  1976-01-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  237-46     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Atropine / pharmacology
Carbachol / pharmacology
Dexetimide / pharmacology*
Drug Interactions
Electric Stimulation
Guinea Pigs
Heart Atria / drug effects
Heart Rate / drug effects
Mathematics
Models, Biological
Parasympatholytics / pharmacology*
Phthalimides / pharmacology*
Piperidines / pharmacology*
Practolol / pharmacology
Quaternary Ammonium Compounds / pharmacology*
Tropanes / pharmacology
Chemical
Reg. No./Substance:
0/Parasympatholytics; 0/Phthalimides; 0/Piperidines; 0/Quaternary Ammonium Compounds; 0/Tropanes; 21888-98-2/Dexetimide; 51-55-8/Atropine; 51-83-2/Carbachol; 51-84-3/Acetylcholine; 6673-35-4/Practolol

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


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