Study on pyridazinone derivative MCI-154 as a cardiotonic agent

The effect of a cardiotonic agent, MCI-154, 6-[4-(4’-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride trihydrate, is a Ca2+ sensitizer on the contractile properties and adenosine triphosphatase ATPase activity on skeletal muscle fibers. As in cardiac m uscle, MCI-154 potentiated isometric tension and improved isometric tension cost at full Ca 2+ activation. However, MCI-154 decreased all the kinetic parameters. The MCI-154 improves not only cardiac systolic function but also diastolic relaxation in CHF. The possible mechanisms are Ca2 + transient and cell shortening in ventricular myocytes and also L-type Ca 2+ current and Na+/Ca 2+ exchange current. The MCI-154 exhibited hemodynamic, inotropic, mechano-energetic and oxidative metabolic effects.