Biomaterial Database

Lipophilicity and pharmacodynamics of cardiotonic steroids in guinea-pig isolated heart muscle preparations. 1988

N Dzimiri, and U Fricke

Pharmakologisches Institut der Universität zu Köln, Fed. Rep. Germany.

1. The inhibitory potency of cardiotonic steroids on myocardial Na+-K+-ATPase increases with increasing lipophilicity. Employing the inotropic action on guinea-pig isolated left atria, the relationship between lipophilicity, chemical structure and the pharmacodynamic properties of cardiac glycosides was further examined. Nineteen digitoxigenin- and digoxigenin-derivatives, whose lipophilic nature and inhibitory effects on the myocardial Na+-K+-ATPase have been previously investigated, were tested. 2. All steroids exhibited positive inotropic effects which varied with the lipophilicity of these drugs. The dependence of the relationship between these two parameters on structural transformations of the steroids showed qualitatively very close parallelism to that between lipophilicity and their inhibitory effects on myocardial Na+-K+-ATPase. 3. The positive inotropic effects and the inhibitory effects on myocardial Na+-K+-ATPase also correlated very well, exhibiting similar patterns in their respective correlations with the individual lipophilicity parameters. 4. It is inferred that (a) the positive inotropic effects of the cardiac glycosides vary with their lipophilicity, exhibiting trends similar to those shown for their inhibitory effects on myocardial Na+-K+-ATPase, (b) this interdependence is secondary to the influence of structural changes, particularly on the steroid nucleus, and (c) both the lipophilic nature and pharmacodynamic behaviour of the cardiac glycosides almost exclusively depend on the steroid nucleus itself.

UI	MeSH Term	Description	Entries
D008055	Lipids	A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)	Lipid
D008297	Male		Males
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D002316	Cardiotonic Agents	Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).	Cardiac Stimulant,Cardiac Stimulants,Cardioprotective Agent,Cardioprotective Agents,Cardiotonic,Cardiotonic Agent,Cardiotonic Drug,Inotropic Agents, Positive Cardiac,Myocardial Stimulant,Myocardial Stimulants,Cardiotonic Drugs,Cardiotonics,Agent, Cardioprotective,Agent, Cardiotonic,Drug, Cardiotonic,Stimulant, Cardiac,Stimulant, Myocardial
D002627	Chemistry, Physical	The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.	Physical Chemistry,Chemistries, Physical,Physical Chemistries
D004071	Digitalis Glycosides	Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis.	Glycosides, Digitalis
D005260	Female		Females
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts