Document Detail


Thiol adducts of ethacrynic acid: a correlation of the rate of liberation of ethacrynic acid with the onset and magnitude of the diuretic response.
MedLine Citation:
PMID:  1123723     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is thought that a derivative of ethacrynic acid (EA) must possess an intact alpha, beta-unsaturated ketone group in order to be capable of eliciting a diuretic response. The 2,3-dimercapto-1-propanol and the cysteine adducts of ethacrynic acid lack such a functional group and still have diuretic activity, especially the cysteine adduct. An in vitro study showed that various thiol adducts of EA liberate EA and the accompanying thiol at a rate that is primarily dependent on the nature of the functional groups present in the thiol portion of the adduct. When the thiol adducts of EA were injected into dogs, the cysteine and mercaptoethylamine hydrochloride adducts which rapidly release EA under specific in vitro conditions were as effective as EA in producing a diuretic response. The onset of action was also similar to that of EA. The thiosalicylic acid adduct of EA releases the accompanying thiol at an intermediate rate in vitro and was less effective than EA in a small dose (3.3 mumol/kg) and the peak response to it was slower to develop. Other adducts that release EA and the accompanying thiol slowly in vitro either produce a very weak response which takes considerable time to develop or are completely devoid of diuretic activity. Thus, the onset and magnitude of the diuretic response produced by various thiol adducts of EA (with the possible exception of the cysteine adduct) are governed primarily by the rate of in vivo release of EA.
Authors:
D A Koechel; E J Cafruny
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  192     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1975 Jan 
Date Detail:
Created Date:  1975-07-01     Completed Date:  1975-07-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  179-94     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Biotransformation
Chlorides / urine
Cysteine / pharmacology
Diuresis / drug effects*
Dogs
Dose-Response Relationship, Drug
Drug Stability
Ethacrynic Acid / analogs & derivatives*,  metabolism,  pharmacology
Female
Male
Potassium / urine
Sodium / urine
Sulfhydryl Compounds*
Sulfides / pharmacology
Time Factors
Chemical
Reg. No./Substance:
0/Chlorides; 0/Sulfhydryl Compounds; 0/Sulfides; 52-90-4/Cysteine; 58-54-8/Ethacrynic Acid; 7440-09-7/Potassium; 7440-23-5/Sodium

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


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