The disappearance of adenosine in blood effect of lidoflazine and other drugs

Abstract

Of 23 different drugs, tested at 1 × 10 −6M, only the three specific coronary vasodilators, lidoflazine, dipyridamole and hexobendine markedly decreased the rate of uptake of addedadenosine by erythrocytes in whole human blood. The inhibitory action of lidoflazine on adenosine permeability of human erythrocyte membranes was much more resistant to repeated washes than that of the two other inhibitors, suggesting the formation of a more stable complex with some unknown erythrocytic membrane component. Plasma or lysed blood adenosine deaminase activity was unaffected by lidoflazine at 1 × 10 −6M, in man and in dogs. The inhibitory effect of lidoflazine on the rate of disappearance of added adenosine from dog whole blood was due to a permeability decreasing action on the platelet membranes; the erythrocytes of the dog were, suprisingly unaffected by the drug. The effect of lidoflazine on the rate of disappearance of added adenosine in whole blood was found to be species dependent. At 10 −7M the drug had a pronounced rate decreasing effect in the chicken, the rabbit, the pig, the human and the dog and a more moderate effect in the guinea-pig. It was virtually ineffective, at 10 t-7M, in the cat, the sheep and the rat. The potency of the drug was directly correlated with the adenosine uptake capacity of the blood corpuscules ( p = 0.002) and inversely correlated with the plasma denosine deaminase activity ( p = 0.008). The adenosine uptake capacity, deaminase activity and lidoflazine sensitivity were qualitatively and quantitatively strikingly similar in the blood of the human and of the pig, suggesting that the pig is a better experimental model for studying the coronary effects of lidoflazine than any one of the seven other speicies studied.