Document Detail

Antiarrhythmic activity of p-hydroxy-N-(2-diethylaminoethyl) benzamide (the p-hydroxy isostere of procainamide) in dogs and mice.
MedLine Citation:
PMID:  836498     Owner:  NLM     Status:  MEDLINE    
p-Hydroxy-N-(2-diethylaminoethyl)benzamide (2), the p-hydroxy isostere of procainamide (1), shows antiarrhythmic activity against acontine-induced atrial arrhythmia and lowers mean arterial blood pressure after iv infusion in dogs. In isolated canine Purkinje fibers, phenolic 2 in a bath concentration of 20 mug/ml significantly reduced the rate of phase O depolarization, prolonged the repolarization time, and reduced automaticity. These in vitro and the above in vivo activities of phenolic 2 were similar to those observed for procainamide (1). Bioisosters, phenolic 2 and procainamide (1), have almost identical respective 13C NMR chemical shifts indicating that electron densities on the respective carbons are very similar. This may explain their similar antiarrhythmic and hypotensive effects. Phenolic 2 and procainamide (1) therapeutic ratios in ICR male mice (acute LD50/ED50 against chloroform hypoxia induced ventricular fibrillation) are 2.1 and 1.8, respectively. Procainamide analogues with electron-donating groups [OH, NH2, NHC(=O)CH3] on the aromatic ring possess more antiarrhythmic activity in mice than the analogue with an electron-withdrawing group (NO2). This indicates that a shift in electron density toward the amide region in the former analogues, as determined by 13C NMR spectroscopy, is one of the factors influencing antiarrhythmic potency in this series.
D E Drayer; B H Slaven; M M Reidenberg; E E Bagwell; M Cordova
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  20     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1977 Feb 
Date Detail:
Created Date:  1977-04-01     Completed Date:  1977-04-01     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  270-4     Citation Subset:  IM    
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MeSH Terms
Action Potentials / drug effects
Anti-Arrhythmia Agents* / blood,  chemical synthesis
Atrial Fibrillation / physiopathology
Mice, Inbred ICR
Myocardial Contraction / drug effects
Procainamide / analogs & derivatives*,  blood,  chemical synthesis,  pharmacology
Purkinje Fibers / drug effects,  physiology
Refractory Period, Electrophysiological / drug effects
Structure-Activity Relationship
Ventricular Fibrillation / physiopathology
Reg. No./Substance:
0/Anti-Arrhythmia Agents; 51-06-9/Procainamide

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