Differential effects of itanoxone--a new hypolipidemic and hypouricemic drug--on platelet and vascular prostaglandin generation in rats.
Itanoxone ((chloro-2'-diphenyl)-4-oxo-4 methylene 2-butyric acid), a newly developed, hypolipidemic and hypouricemic compound with moderate anti-inflammatory activity, showed a short-lived, dose-dependent (20--200 mg/kg, orally), apparently competitive inhibition of platelet malondialdehyde (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. Pretreatment with itanoxone partially prevented the inhibitory effect of aspirin on both platelet and vascular prostaglandin synthesis. This suggests that itanoxone--like aspirin--acts at the level of cyclo-oxygenase but with greater selectivity on the platelet enzyme. This pharmacological activity is of great theoretical interest for the potential use of this compound as an antithrombic drug.
D000818:Animals; D001241:Aspirin / Q000037:antagonists & inhibitors; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D002090:Butyrophenones / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D013929:Thromboxane B2 / Q000096:biosynthesis; D014528:Uricosuric Agents / Q000494:pharmacology*
D001713:Biphenyl Compounds; D002090:Butyrophenones; D000960:Hypolipidemic Agents; D011453:Prostaglandins; D014528:Uricosuric Agents; C024140:itanoxone; D008315:Malondialdehyde; D013929:Thromboxane B2; D001241:Aspirin