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 [3H]ouabain binding in guinea-pig cardiac membranes correlates well with their effects on myocardial contractile force. However, the latter effect was exerted by tenfold 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.
Herzig
S
S
Institute of Pharmacology, University of Kiel, Fed. Rep. of Germany.
Heber
D
D
Mescheder
A
A
Reifenstein-Herzig
U
U
Thormann
T
T
Verborg
M
M
Mohr
K
K
D000818:Animals; D002264:Carboxylic Acids / Q000493:pharmacokinetics*; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000493:pharmacokinetics; D011869:Radioligand Assay; D013552:Swine
D002264:Carboxylic Acids; D002316:Cardiotonic Agents; D010042:Ouabain