Effect of some new cardiotonic agents on synaptosomal sodium uptake

The new positive inotropic agents sulmazole, piroximone, milrinone and 1,5-dihydro-6-chloro-3-methy-limidazo [2,1-b]quinazolone-2 enhance 22Na uptake in rat brain synaptosomes. In comparison, theophylline, a cyclic nucleotide phosphodiesterase inhibitor, has no effect on synaptosomal 22Na uptake. Tetrodotoxin inhibits the stimulation induced by the new inotropic agents. The quinazolone is about three times more potent than protoveratrine B and milrinone and ten times more potent than sulmazole and piroximone. There is a direct correlation between the 22Na uptake and the positive inotropic effect on guinea pig left atria of the new cardioactive drugs. The dose-response curves for synaptosomal 22Na uptake and for the inotropic effect on guinea pig left atria are parallel for sulmazole and the quinazolone drug, with first an increase and then a decrease in activity.