In Vitro

In vitro, Omecamtiv mecarbil selectively activates cardiac myosin by increasing the myosin ATPase rate. ^[1] In isolated cardiac myocytes, Omecamtiv mecarbil results in increase of myocyte contractility and overcomes of the myosin inhibitor BDM without increasing the calcium transient or inhibiting the PDE pathway. ^[1]

In Vivo

Omecamtiv mecarbil significantly increases fractional shortening starting at 0.4 mM plasma concentrations in SD rats, sham animals and in rats with heart failure. ^[1] In conscious dogs with myocardial infarction (MI-sHF), Omecamtiv mecarbil leads to a significant increase in wall thickening (25%), stroke volume (44%), cardiac output (22%) and left ventricular (LV) systolic ejection time (26%). In addition, Omecamtiv mecarbil also results in the decreases of some hemodynamic parameters including heart rate, mean left atrial pressure, and LV end-diastolic pressure. In conscious dogs with left ventricular hypertrophy (LVH-sHF), Omecamtiv mecarbil leads to similar and not statistically different effects on hemodynamic parameters. ^[2]

Clinical Trials

Omecamtiv mecarbil is currently in Phase II clinical trials in patients with Left Ventricular Systolic Dysfunction Hospitalized for Acute Heart Failure.

Features