Antiarrhythmic activity of alpha-tocopherol nicotinate and related compounds and their physico-chemical properties.
The effect of alpha-tocopherol nicotinate (Renascin), alpha-tocopherol and dodecanoic acid (lauric acid) on the positive inotropic action of ouabain and digoxin and on cardiac glycoside induced arrhythmias has been tested in isolated guinea-pig left atria and in anaesthetized guinea-pigs. alpha-Tocopherol nicotinate and dodecanoic acid significantly decrease the positive inotropic action of digoxin, but not that of ouabain in isolated guinea-pig atria. Ouabain and digoxin induced arrhythmias are suppressed by the three compounds in isolated guinea-pig atria and in anaesthetized guinea-pigs: alpha-tocopherol nicotinate has the highest antiarrhythmic activity followed by dodecanoic acid and alpha-tocopherol. These results are further evidence for the dissociation between the positive inotropic and arrhythmogenic action of cardiac glycosides. The antiarrhythmic activity of the three compounds and the physico-chemical properties, as measured in liposomes, are compared with that of quinidine and aprindine. As nicotinic acid does not show any effect on cardiac glycoside induced arrhythmias, the ester linkage in alpha-tocopherol nicotinate seems to be of particular importance for its antiarrhythmic activity.
Schlieper
P
P
Institut für Pharmakologie, Universität Düsseldorf, Fed. Rep. of Germany.
Tawfik
H
H
D000758:Anesthesia; D000818:Animals; D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004077:Digoxin / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008081:Liposomes; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009539:Nicotinic Acids / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010316:Particle Size; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000959:Antihypertensive Agents; D008081:Liposomes; D009539:Nicotinic Acids; D014810:Vitamin E; C012581:alpha-tocopheryl nicotinate; D010042:Ouabain; D004077:Digoxin