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  • Title: In vitro and in vivo studies of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)- quinolinone (OPC-8212), a novel positive inotropic drug, in various animals.
    Author: Yamashita S, Hosokawa T, Kojima M, Mori T, Yabuuchi Y.
    Journal: Arzneimittelforschung; 1984; 34(3A):342-6. PubMed ID: 6331464.
    Abstract:
    The cardiovascular effects of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) were investigated in isolated ventricular muscles of various mammalian species, anaesthetized dogs and conscious dogs. In the isolated ventricular muscles of the dog, cat, rabbit and guinea pig, OPC -8212 (3 X 10(-6)-3 X 10(-4) mol/l) increased the developed tension in a concentration-related manner and these positive inotropic effects of OPC -8212 were 1/140-1/120 those of dobutamine but 5-17 times and 8-25 times those of amrinone and theophylline, respectively. The positive inotropic effect of OPC -8212 was not modified by pindolol or phentolamine. In the isolated rat ventricular muscle, OPC -8212, amrinone and theophylline exerted no positive inotropic effect, although dobutamine did. In anaesthetized dogs, OPC -8212 (0.1-3 mg/kg i.v.) was nearly as active as amrinone in producing an increase in left ventricular contractile force. However, OPC -8212 was much less active than amrinone in increasing heart rate and decreasing blood pressure. In conscious dogs OPC -8212 at doses of 1 and 3 mg/kg i.v. increased peak LV dP/dt by 27% and 59%, respectively, without significant changes in heart rate and blood pressure. OPC -8212 did not affect the dog heart Na+,K+-ATPase activity. These results suggest the following: (1) OPC -8212 has a mechanism of action different from those of catecholamines and cardiac glycosides, (2) it has a useful profile in the treatment of heart failure because it caused a selective positive inotropic effect with no obvious positive chronotropic and vascular effects.
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