PHARMACOLOGICAL CHARACTERIZATION OF POSITIVE INOTROPIC DERIVATIVES OF 4-AMINO-7-METHYL-1,8-NAPHTHYRIDINE-3-CARBOXYLIC ACID

The positive inotropic effect of a series of 4-amino-7- methyl-1,8-naphthyridine-3-carboxylic acid derivatives was compared with the effects of known inotropic agents (ouabain, dihydroouabain, isoproterenol, adrenaline, histamine and isobutylmethylxanthine) in guinea-pig atrial and ventricular myocardial preparations. With respect to their functional effects the 1,8-naphthyridine compounds are clearly different from drugs acting on the cAMP system, whereas several similarities with cardiac glycoside effects were found. Their ability to inhibit [H-3]ouabain binding in guinea-pig cardiac membranes correlates well with their effects on myocardial contractile force. However the latter effect was exerted by ten-fold lower concentrations. The dissimilarities found between the 1,8-naphthyridines and digitalis may be due to a different type of interaction with the binding site on the (Na++K+)-ATPase.