A novel positive inotropic series. 1st communication: in vitro studies of 3-, 4-, 5-, 6-, 7- and 8-pyridyl-2(1H)-quinolone derivatives.

A series of 3-, 4-, 5-, 6-, 7- and 8-pyridyl-2(1H)-quinolones and related compounds were evaluated for positive inotropic and vasodilatory activities in vitro. Most of them produced dose-related increases in myocardial contractility on guinea pig isolated atria and perfused heart. In guinea pig atria, the 6-pyridyl molecules were more active than the 5-pyridyl ones; the mean ED50 of compounds 14, 32 and 33 was 4.0 x 10(-7) mol/l i.e. 33 times that of sulmazole; that of compounds 6 and 7 was 2.0 x 10(-5) mol/l. The potencies of the 5- and the 6-pyridyl series also differed by 2 log units on perfused guinea pig heart. The 5- and 6-pyridyl series induced relaxation in precontracted pig coronary artery and coronary vasodilation on perfused guinea pig heart. Compounds 14, 32 and 33 also showed alpha-adrenolytic properties, which were by 0.7 log unit lower than that of phentolamine. These results indicate that this novel cardiotonic series exert positive inotropic and coronary vasodilatory effects.