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J Pharm Pharmacol. 1993 Aug;45(8):715-9.

Dual inhibition of platelet-activating factor and arachidonic acid metabolism by ajmaline and effect on carrageenan-induced rat paw oedema.

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  • 1Department of Pharmacology, Aga Khan University, Karachi, Pakistan.

Abstract

The effects of ajmaline on human platelet aggregation, arachidonate metabolism and platelet activating factor (PAF)-induced lethality in rabbits were examined. Platelet aggregation induced by several stimuli (ADP, collagen, and PAF) was inhibited by increasing concentrations of ajmaline. The potency of ajmaline was higher when PAF was employed as stimulating agent in comparison with other agonists (IC50 70, 270 and 380 microM for PAF, ADP and collagen, respectively) whereas ajmaline had no effect against arachidonic acid-induced aggregation. In contrast however, ajmaline inhibited arachidonate metabolism by platelet homogenates. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraenoic acid was inhibited by ajmaline with comparable potencies. Pretreatment of rabbits with ajmaline (50 mg kg-1) completely abolished the lethal effects of PAF (11 micrograms kg-1) given intravenously (P < 0.001). In addition, ajmaline at doses ranging from 50 to 100 mg kg-1 inhibited carrageenan-induced rat paw oedema (P < 0.001). In this test ajmaline was three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF antagonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygenase enzymes with anti-inflammatory properties.

PMID:
7901369
[PubMed - indexed for MEDLINE]
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