Cardiovascular effects of an antiarrhythmic aminosteroid ORG 6001 in the anesthetized pig.
The hemodynamic effects of 3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride (ORG 6001), an aminosteroid possessing antiarrhythmic properties, were studied in 14 anesthetized pigs. ORG 6001 was administered i.v. cumulatively until a toxic level was reached. Doses less than 20mg/kg had, in spite of the negative inotropic properties of ORG 6001, no effect on the pump function of the heart, as the afterload was reduced and the filling pressure was not significantly altered. After administration of 40 mg/kg A-V conduction was depressed and second degree A-V block appeared. This was associated with deterioration of the pump function and for 6 of the 14 animals this was fatal. In the survivors, the alterations were reversible after cessation of drug administration. Since ORG 6001 has been shown to be effective against arrhythmias at doses less than 20 mg/kg, though in a different species (dog), it seems likely that it can be used safely for antiarrythmic treatment.
D015068:17-Ketosteroids / Q000494:pharmacology; D000731:Androstanes / Q000494:pharmacology*; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D015068:17-Ketosteroids; D000731:Androstanes; D000889:Anti-Arrhythmia Agents