Inotropic activity of hydroindene amidinohydrazones
Détails
ID Serval
serval:BIB_803D144992C8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Inotropic activity of hydroindene amidinohydrazones
Périodique
Journal of Medicinal Chemistry
ISSN
0022-2623 (Print)
Statut éditorial
Publié
Date de publication
01/2002
Volume
45
Numéro
1
Pages
127-36
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 3
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 3
Résumé
Several hydroindenic derivatives (7a-methyl-2,3,5,6,7,7a-hexahydro-1H-indenes), bearing an amidinohydrazone at C-5 and different moieties at C-1, have been synthesized and evaluated for their inotropic and chronotropic effects on right- and left-guinea-pig-atria activity. Three of them showed the same profile as digoxin, although with lower potency. The effect on Na(+),K(+)-ATPase (NKA) was also evaluated for these three compounds, observing that two of them, with the same absolute configuration as natural cardenolides, are also NKA inhibitors, while the compound with the opposite configuration lacks such an effect. More interestingly, both active compounds act without affecting the cardiac rhythm. This could be related to the selective inhibition of the human alpha2beta1 isozyme (associated with the inotropic effect) with respect to the alpha1beta1 isozyme (associated with the maintenance of basal ionic levels in the cell and the toxic effect of cardenolides).
Mots-clé
Amidines/chemical synthesis/chemistry/pharmacology
Animals
Biological Transport
Cardiotonic Agents/*chemical synthesis/chemistry/pharmacology
Enzyme Inhibitors/chemical synthesis/chemistry/pharmacology
Female
Guinea Pigs
Heart/drug effects/physiology
Heart Rate
Humans
Hydrazones/*chemical synthesis/chemistry/pharmacology
Indenes/*chemical synthesis/chemistry/pharmacology
Isoenzymes/metabolism
Male
Myocardial Contraction
Na(+)-K(+)-Exchanging ATPase/antagonists & inhibitors/metabolism
Oocytes/metabolism
Rats
Transfection
Xenopus laevis
Pubmed
Web of science
Création de la notice
24/01/2008 13:28
Dernière modification de la notice
20/08/2019 15:40