Cardiopulmonary effects of antimalarial drugs: Coronary vascular effects of pyridoquinolines

Abstract

The prototype pyridoquinoline compound used in this investigation was azacrin (2-methoxy-7-chloro-10[4,diethylamino-1-methylbutylamino]-pyrido[3,2- b]-quinoline). In the anesthetized dog, azacrin, quinacrine and primaquine had a similar cardiopulmonary pattern of effects: no change in pulmonary resistance and compliance, cardiac depression and a decrease in coronary vascular resistance. The decrease in coronary vascular resistance was independent of myocardial depression because in the perfused ventricular segment that was fibrillating each of the 3 drugs still produced its vascular effect. All 3 drugs exerted an antiarrhythmic effect in mice and antagonized the cardiac effects of adenosine in rats. There was no pharmacologic action that was characteristic of the pyridoquinoline, 8-aminoquinoline or aminoacridine group. The second pyridoquinoline compound was WR 10,488 (2- N-butoxy-7,10-dichloropyrido[3,2- b]quinoline). It suppressed the parasitemia of mice infected with Plasmodium berghei. WR 10,488 depressed the excitability of the isolated atrial muscle of the rat, prevented ventricular fibrillation in mice and reduced cardiac output in dogs. These signs of cardiac depression produced by WR 10,488 are not unique but are effects expected of aminoacridines, 8-aminoquinolines and pyridoquinolines.