Investigations of the mode of action of a new antidysrhythmic drug, Kö 1173

Summary 1 Kö 1173, 1‐(2′,6′‐dimethyl‐phenoxy)‐2‐amino‐propane, was equal to lignocaine in potency as a local anaesthetic on stripped frog sciatic nerve at pH 7·5. 2 In anaesthetized guinea‐pigs in which ventricular fibrillation had been produced by an intravenous infusion of ouabain, intravenous adm...

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Bibliographic Details
Published in:British journal of pharmacology 1972-01, Vol.44 (1), p.1-9
Main Authors: SINGH, B. N., WILLIAMS, E. M. VAUGHAN
Format: Article
Language:English
Subjects:
Action Potentials - drug effects
Anesthetics, Local - pharmacology
Animals
Anti-Arrhythmia Agents - pharmacology
Anura
Bradycardia - chemically induced
Guinea Pigs
Heart Atria - drug effects
Heart Conduction System - drug effects
Heart Rate - drug effects
In Vitro Techniques
Injections, Intravenous
Lidocaine - pharmacology
Muscle Contraction - drug effects
Ouabain - antagonists & inhibitors
Ouabain - toxicity
Phenols - pharmacology
Propylamines
Rabbits
Sciatic Nerve - drug effects
Systematic Pharmacology
Time Factors
Ventricular Fibrillation - prevention & control
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Summary:Summary 1 Kö 1173, 1‐(2′,6′‐dimethyl‐phenoxy)‐2‐amino‐propane, was equal to lignocaine in potency as a local anaesthetic on stripped frog sciatic nerve at pH 7·5. 2 In anaesthetized guinea‐pigs in which ventricular fibrillation had been produced by an intravenous infusion of ouabain, intravenous administration of Kö 1173 caused reversion to sinus rhythm in ten out of ten animals. The mean dose of Kö 1173 required was 3·3 mg (15·3 μmol)/kg. When the ouabain infusion was continued, ventricular fibrillation did not recur, and the lethal dose of ouabain was greater than in controls. 3 Pretreatment with Kö 1173, however, did not influence the toxicity of ouabain infusion, implying great brevity of action. 4 Kö 1173 given intravenously caused a bradycardia which was maximal in 2–3 min, and which did not last more than 5 minutes. 5 Kö 1173 reduced the maximum driven frequency of isolated rabbit atria, raised electrical threshold, slowed conduction velocity and depressed contractions. 6 Kö 1173 reduced the maximum rate of depolarization of intracellularly recorded rabbit atrial and ventricular potentials, but did not affect the resting potential or the duration of the action potential.
ISSN:0007-1188
1476-5381
DOI:10.1111/j.1476-5381.1972.tb07232.x