NSP-805 is a potent and selective inhibitor of guinea pig cardiac phosphodiesterase 3 (PDE3).

In isolated guinea pig left atria, the positive inotropic EC50 values (microM) ranked by potency were approximately 0.18 (NSP-805), 0.39 (indolidan), 1.1 (MCI-154), 1.7 (NSP-804, milrinone), 2.0 (denopamine), 4.0 (papaverine), 4.4 3-isobutyl-1-methylxanthine (IBMX), 6.5 (imazodan), and 27 (amrinone)[1].

In anesthetized dogs, intravenous (i.v.) injection of NSP-804 and NSP-805 produced dose-dependent increases in left ventricular VVdp/dtmax and decreases in aortic blood pressure (ABP) with relatively small increases in heart rate (HR). The ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, denopamine, milrinone, MCI-154, and indolidan were 15, 12, 22, 23, 15, and 7.3, respectively. When administered intraduodenally to anesthetized dogs, the ED50 values (micrograms/kg) for LVdP/dtmax of NSP-804, NSP-805, milrinone, and indolidan were approximately 30, 10, 200, and 25, respectively. In the propranolol-induced heart failure model, NSP-804 and NSP-805 completely normalized the hemodynamic state. The in vitro positive inotropic effects of NSP-804 and NSP-805 were accompanied by increases in tissue cyclic AMP and abolished by carbachol. NSP-805 was the most potent and selective inhibitor of guinea pig cardiac phosphodiesterase (PDE) III among the agents examined, while NSP-804 was a potent and selective inhibitor of PDE III similar to indolidan[1].