Antiarrhythmic activity of p-hydroxy-N-(2-diethylaminoethyl) benzamide (the p-hydroxy isostere of procainamide) in dogs and mice.

doi:10.1021/JM00212A017

Paper

Antiarrhythmic activity of p-hydroxy-N-(2-diethylaminoethyl) benzamide (the p-hydroxy isostere of procainamide) in dogs and mice.

Published Feb 1, 1977 · D. Drayer, B. Slaven, M. Reidenberg

Journal of medicinal chemistry

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5

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Abstract

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.

In Vitro Study

Study Snapshot

Phenolic 2 shows antiarrhythmic and hypotensive effects in dogs and mice, with similar properties to procainamide (1), suggesting similar electron densities on their carbons.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Antiarrhythmic activity of p-hydroxy-N-(2-diethylaminoethyl) benzamide (the p-hydroxy isostere of procainamide) in dogs and mice.

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References

Citations

Clinical Consequences of the Lipophilicity and Plasma Protein Binding of Antiarrhythmic Drugs and Active Metabolites in Man

Antiarrhythmic drugs with higher lipophilicity may experience more central nervous system side effects, while hydrophilic drugs may have less protein binding and less brain tissue penetration.

Comparison of Antiarrhythmic Effects of Procainamide, N-Acetylprocainamide, and p-Hydroxy-N-(3-diethylaminopropyl)benzamide

P-hydroxy-N-(3-diethylaminopropyl)benzamide (PP) has antiarrhythmic potency and efficacy intermediate to procainamide and N-acetylprocainamide (NAPA).

Prevention of chloroform-induced ventricular tachycardia in mice as an index of antiarrhythmic activity.

The revised screening technique for antiarrhythmic activity in mice effectively predicts antiarrhythmic activity and provides information on potential CNS side effects.

Steady‐state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function

Quinidine, its metabolites, and their metabolites contribute to its antiarrhythmic effects in cardiac patients, with varying degrees of renal function.