Hemodynamic properties of a new quinidine analog, cupreidine (6'-hydroxycinchonine).
Cupreidine 96'-hydroxycinchonine) is a recently synthesized analog of quinidine (6'-methoxycinchonine). Previous studies in mice have shown that quinidine and cupreidine have equivalent antiarrhythmic potencies, whereas the acute toxicity of cupreidine is about 50% less than that of quinidine. Many of the serious adverse effects of quinidine are due to undesirable cardiovascular properties. We have, therefore, compared the effects of the two drugs on blood pressure, heart rate, and peripheral vasodilation in rats, and on myocardial contractility in isolated rabbit hearts at a series of comparable doses. Quinidine produces a more marked bradycardia and depression of blood pressure than does cupreidine. The vasodilation produced by intraarterial administration of quinidine was significantly greater than cupreidine. Furthermore, quinidine elicited a greater negative inotropic effect. Cupreidine exhibited a much more favorable hemodynamic profile than quinidine with regard to the properties that were examined. These results, coupled with the fact that cupreidine has significant antiarrhythmic activity and a lower acute toxicity profile, suggest that this drug may be useful in the therapy of cardiac arrhythmias.
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects*; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D011802:Quinidine / Q000009:adverse effects; D011803:Quinine / Q000009:adverse effects / Q000031:analogs & derivatives*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D014655:Vascular Resistance / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; C029819:6'-hydroxycinchonidine; D011803:Quinine; D011802:Quinidine