EXPERIMENTAL STUDIES ON RELATIONSHIP OF CHEMICAL STRUCTURE OF PROTOCATECHUIC ACID DEIRVATIVES AND CARDIAC OXYGEN CONSUMPTION AND CORONARY FLOW

In an earlier paper we reported that administration of protocatechuic acid (PAC), isolated from leaves of Ilex chinensis Sims, decreased myocardial oxygen consumption in cats and increased tolerance to anoxia in rat heart-lung preparations. In this paper, three groups of PAC derivatives were studied on their influence on cardiac oxygen consumption and coronary flow in open chest cats. The first group of compound, PAC-1, was obtained by neutralizing PAC with tetramethylpyrazine. PAC-1 decreased the myocardial oxygen consumption with a potency higher than that of PAC, but didn't influence the coronary flow. On the contrary, tetramethyl pyrazine at the same dosage increased the coronary flow and didn't decrease the myocardial oxygen consumption. Three compounds of the second group were PAC derivatives bearing various functionary moieties of β-receptor blocking agents, namely: 7704-1: 1-(2-methoxy-4-methoxycarbonyl-1-phenoxy) 3-isopropyl-amino-2-propanol, 7704-T: 1-(2-methoxy-4-methoxycarbonyl)-3-tertiary butylamino-2-propanol, 7704-H: 1-(2-methoxyl-4-methoxycarbonyl-1-phenoxy)-3-(3,4-dimethoxy phenyl ethyl amino)-2-propanol. Their effects on myocardial oxygen consumption, coronary flow, arterial pressure and heart rate were similar to that of praetolol but weaker in potency. Two compounds of the third group were isomers of PAC, namely, 2,5-dihydrobenzoic acid and 2,6-dihydrobenzoic acid. Both drugs increased tolerance to anoxia in intact mice, but didn't influence tbe cardiac oxygen consumption and coronary flow.