The effect of a new positive inotropic agent, 3, 4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-qu inolinone (OPC-8212), on thin bundles of skinned fibers from cardiac muscle.

The effect of 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212), a new positive inotropic agent, on the contractile system and the sarcoplasmic reticulum (SR) was examined by using thin bundles of chemically skinned fibers from ventricular trabeculae of the guinea pig and the African clawed toad. Sulfolane , the solvent of OPC -8212 used in the present experiments, slightly increased the Ca-sensitivity of the contractile system of cardiac skinned fibers, and decreased the maximum tension developed at high enough concentrations of Ca. OPC -8212 up to 300 mumol/l did not add any further effects. Initial rate of Ca uptake by the SR was not affected by 300 mummol /l OPC -8212 plus 0.6% sulfolane . The Ca-sensitivity of the Ca-induced Ca release mechanism in the SR was increased by 0.6% sulfolane but no further effect was observed by an addition of OPC -8212 up to 300 mumol/l. Thus, no direct effect of 300 mumol/l OPC -8212 per se was found on the contractile system or the SR. In view of these findings, the mechanism of positive inotropic action of OPC -8212 was discussed.