DUAL INHIBITION OF PLATELET-ACTIVATING-FACTOR AND ARACHIDONIC-ACID METABOLISM BY AJMALINE AND EFFECT ON CARRAGEENAN-INDUCED RAT PAW EDEMA

The effects of ajmaline on human platelet aggregation, arachidonate me tabolism and platelet activating factor (PAF)-induced lethality in rab bits were examined. Platelet aggregation induced by several stimuli (A DP, collagen, and PAF) was inhibited by increasing concentrations of a jmaline. The potency of ajmaline was higher when PAF was employed as s timulating agent in comparison with other agonists (IC50 70, 270 and 3 80 muM for PAF, ADP and collagen, respectively) whereas ajmaline had n o effect against arachidonic acid-induced aggregation. In contrast how ever, ajmaline inhibited arachidonate metabolism by platelet homogenat es. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraeno ic acid was inhibited by ajmaline with comparable potencies. Pretreatm ent of rabbits with ajmaline (50 mg kg-1) completely abolished the let hal effects of PAF (11 mug kg-1) given intravenously (P < 0.001). In a ddition, ajmaline at doses ranging from 50 to 100 mg kg-1 inhibited ca rrageenan-induced rat paw oedema (P < 0.001). In this test ajmaline wa s three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF anta gonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygena se enzymes with anti-inflammatory properties.