title: Inotropic activity of hydroindene amidinohydrazones.
abstract: 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).
authors.affiliation: Facultad de Farmacia, Laboratorio de Química Orgánica y Farmacéutica, Campus Miguel de Unamuno, E-37007 Salamanca, Spain.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Sevillano
authors.forename: Concepción P
authors.initials: CP
authors.lastname: Melero
authors.forename: Esther
authors.initials: E
authors.lastname: Caballero
authors.forename: Fernando
authors.initials: F
authors.lastname: Tomé
authors.forename: Lionel G
authors.initials: LG
authors.lastname: Lelièvre
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
authors.forename: Rosalía
authors.initials: R
authors.lastname: Carrón
authors.forename: Manuel
authors.initials: M
authors.lastname: Medarde
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000578:Amidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002316:Cardiotonic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D009200:Myocardial Contraction; D009865:Oocytes / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D014162:Transfection; D014982:Xenopus laevis
chemical_list: D000578:Amidines; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D006835:Hydrazones; D007192:Indenes; D007527:Isoenzymes; D000254:Sodium-Potassium-Exchanging ATPase