Fifteen quinolizidine derivatives have been tested for antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig (gp) heart tissues and to assess calcium antagonist activity. All compounds exhibited from moderate to high antiarrhythmic activity, and five of them (3, 4, 6, 13, and 15) were more active and potent than the reference drugs (amiodarone, lidocaine, procainamide, and quinidine). These compounds were studied on spontaneously beating Langendorff-perfuse gp heart; even at concentration 17-67 times higher than the corresponding EC(50) for antiarrhythmic activity, they prolonged the QT intervals only moderately, comparing favorably with amiodarone and quinidine. Compounds 3 and 15 deserve further investigation due to their interesting cardiovascular profiles.
|Titolo:||Novel quinolizidinyl derivatives as antiarrhythmic agents: 2. Further investigation|
|Parole Chiave:||pharmacological interest; atrial-fibrillation; receptor antagonists; 1-lupinylquinoxalin-2(1H)-ones; metoclopramide; arrhytmias; lupinne; ligands; drugs; 5-HT3|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
Settore BIO/14 - Farmacologia
|Data di pubblicazione:||24-giu-2010|
|Digital Object Identifier (DOI):||10.1021/jm100298d|
|Appare nelle tipologie:||01 - Articolo su periodico|