Effects of a new forskolin derivative, NKH477, on canine ventricular arrhythmia models

J Cardiovasc Pharmacol. 1993 Dec;22(6):847-51. doi: 10.1097/00005344-199312000-00011.

Abstract

Using two-stage coronary ligation-, digitalis- and epinephrine-induced canine ventricular arrhythmia models, we examined whether a new positive inotropic agent, NKH477, 6-(3-dimethylaminopropionyl)forskolin hydrochloride, a water-soluble derivative of forskolin, had deleterious effects on arrhythmias. NKH477 increased heart rate (HR) and decreased blood pressure (BP) in dogs with all the arrhythmia models. Unexpectedly, NKH477 suppressed digitalis- and epinephrine-induced arrhythmias, but did not suppress two-stage coronary ligation arrhythmia or aggravate it. These results indicate that NKH477, unlike other new positive inotropic agents such as amrinone, milrinone, sulmazole and vesnarinone, did not worsen these arrhythmias; thus, NKH477 may be a useful positive inotropic agent with little arrhythmogenic effect.

MeSH terms

  • Analysis of Variance
  • Animals
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / drug therapy*
  • Blood Pressure / drug effects*
  • Colforsin / administration & dosage
  • Colforsin / analogs & derivatives*
  • Colforsin / blood
  • Colforsin / pharmacology
  • Colforsin / therapeutic use
  • Disease Models, Animal
  • Dogs
  • Electrocardiography / drug effects
  • Epinephrine / pharmacology
  • Female
  • Heart Rate / drug effects*
  • Injections, Intravenous
  • Male
  • Myocardial Contraction / drug effects
  • Ouabain / pharmacology
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*

Substances

  • Vasodilator Agents
  • Colforsin
  • Ouabain
  • Epinephrine