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- W2010489357 abstract "Abstract The cardiovascular properties of bemarinone (5, 6‐dimethoxy‐4‐methyl‐2‐(1H)‐quinazolinone), a new chemical entity with positive inotropic and vasodilator activity, were investigated. Bemarinone (10 −6 −10 −3 M) selectively increased contractile force 144 ± 15% in electrically paced guinea pig left atria while marginally affecting sinus rate (16 ± 13%, peak effect) in spontaneously beating right atria. In anesthetized dogs, bemarinone (0.125–0.875 mg/kg, i.v.) increased myocardial contractile force (21–114%) and left ventricular dP/dt max (7–45%) in a dose‐related manner. Selective inotropic activity was observed in vivo since no significant change in mean arterial pressure or heart rate occurred at a 50% increase in contractile force (ED 50 = 0.23 mg/kg). In conscious instrumented dogs, oral administration of bemarinone (2.5–10 mg/kg) produced peak increases in left ventricular dP/dt max ranging from 28% to 87% (ED 50 = 3.7 mg/kg). The onset of positive inotropic activity after 10 mg/kg p.o. occurred within 5 min, and the duration exceeded 3 hr. Bemarinone decreased mean arterial blood pressure (0.4–16%) via a reduction in total peripheral resistance. Direct vascular effects were observed in vitro since bemarinone relaxed rabbit aortic strips contracted with phenylephrine or KCl. In an acute model of ischemic left ventricular failure, bemarinone increased cardiac output (41%) and stroke volume (34%) while reducing left ventricular end diastolic pressure (63%) and total peripheral resistance (29%) without significantly changing mean arterial pressure or heart rate. The positive inotropic effect of bemarinone was not antagonized by propranolol and atropine pretreatment. The compound selectively and competitively inhibited cyclic AMP phosphodiesterase fraction III from canine ventricle (K i = 15.8.μM). In summary, bemari none is an orally active, positive inotropic and vasodilator agent with potential clinical utility in the management of congestive heart failure." @default.
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- W2010489357 title "Cardiovascular properties of bemarinone: A new orally active quinazolinone cardiotonic agent" @default.
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