Itanoxone, An Inhibitor Of Cyclo-Oxygenase, Acts Preferentially On Platelet Than On Vascular Enzyme

Several attaints have been made to dissociate the inhibitory effects of aspirin on platelet and vascular cells, but no definite results have been obtained. Other drugs, presumably acting on cyclo-oxygenase, are therefore being investigated for their relative inhibitory effect on platelet and vascular prostaglandin synthesis.

The present study was performed in male CD-COBS rats. Itanoxone [ (chloro-2' -diphenyl) -4-oxo-4 methylene 2-butyric acid ], a newly developed, hypolipidemic and hypouricemic compound with moderate anti-inflanmatory activity, showed a short lived, dose dependent (20-200 mg/kg, orally) apparently competitive inhibition of platelet MDA stimulated by either thrombin or arachidonic acid. Repeated doses did not result in any cumulative effect. At doses which completely blocked MDA production, itanoxone also inhibited thrombin-stimulated thromboxane B₂ production in platelets but had no measurable effect on vascular prostacyclin generation measured both by a bioassay and a radioimmunoassay of its stable derivative 6-Keto-PGF_1α . Pretreatment with itanoxone partially prevented therrhibitory effect of aspirin on both platelet and vascular prostaglandin synthesis. This suggests that itanoxone - like aspirin - acts at the level of cyclo-oxygenase but has much greater selectivity on the platelet enzyme.

This pharmacological activity is of great theoretical interest for potential use of this compound as an antithrombotic drug.