Five methoxy-2-methyl-3-indole acetic acid. A metabolite and alkali hydrolysis product of indomethacin, markedly inhibits platelet aggregation only in the presence of aorta or a product released by aorta.

W I Rosenblum, B Landa

Index: Prostaglandins. Leukot. Med. 8(2) , 125-32, (1982)

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Abstract

5-methoxy-2-methyl-3-indole acetic acid (5MIAA) is a metabolite and alkali hydrolysis product of indomethacin. This indole derivative was previously found to be an effective in vivo inhibitor of platelet aggregation in an experimental model of microvascular injury in the mouse. In a standard aggregometer assay, the in vitro inhibitory action of 5MIAA was weak and failed to explain its in vivo effect. The present study employed two assay systems testing the capacity of 5MIAA to increase the aggregate inhibiting activity of the aorta. In one series of experiments the aorta, the drug and platelet rich plasma were incubated together, and in another series aliquots of aortic incubation media were transferred to PRP. Both types of study showed that 5MIAA interacts with the aorta and with a substance(s) produced by aortic wall to markedly inhibit aggregation stimulated by arachidonic acid. Thus, when 100 micrograms/ml of 5MIAA, which by itself had a negligible effect on aggregation, was added to a cuvette containing both aorta and PRP, the inhibitory effect of the aorta was enhanced three fold. The substance with which 5MIAA interacts was eliminated by cyclooxygenase inhibitors, but direct tests of 5MIAA's ability to potentiate the effect of prostacyclin were unsuccessful.