Antithrombotic Effect of Monamine Oxidase Inhibitor (Nialamide)

Abstract

A new type of antithrombotic substance, nialamide, was compared with phenindione and warfarin in its preventive effect against experimental thrombosis produced in rabbits. One hundred fifty-seven rabbits were subjected to quantitative traumatization of the endothelial surface of the retroauricular artery and marginal vein of the ear. Pretreatment of animals with 3 to 5 mg./Kg. of nialamide, which did not prolong the one-stage prothrombin time, was much more effective in preventing thrombosis than either phenindione or warfarin, both of which prolonged the prothrombin time markedly. Even in the animals pretreated by 600 to 900 mg. of phenindione, which reduced the prothrombin activity to less than 6 per cent, the preventive effect of phenindione is significantly less than the antithrombotic effect of 3 to 5 mg./Kg. of nialamide. Pretreatment of animals with 1.5 mg./Kg. of nialamide was found to be ineffective. However, the concomitant application of subeffective doses of both phenindione, 150 mg., and nialamide, 1.5 mg., was found to be effective. On the other hand, the addition of phenindione, even in doses as large as 300 to 900 mg., to an effective dose of nialamide, 3 to 5 mg./Kg., did not further enhance the antithrombotic effect of nialamide. The antithrombotic effect of nialamide was not shown to be significantly modified by sympathectomy or by denervation of the blood vessels tested. Nialamide was found to prevent the aggregation of platelets on the injured endothelial surface.