title: Prostaglandin synthetase inhibitors. Drugs which affect arachidonic acid metabolism.
abstract: Drugs may alter prostaglandin production by acting on the various pathways of arachidonic acid metabolism. The liberation of arachidonic acid from membrane-bound phospholipids, induced by the enzyme phospholipase A2, may be inhibited by mepacrine and the steroidal anti-inflammatory agents. The bio-transformation of the free arachidonic acid, by the enzyme cyclooxygenase, to the unstable endoperoxide intermediates is inhibited by non-steroidal anti-inflammatory agents. Thus, the generation of all the prostaglandin products is prevented. This action can explain the anti-inflammatory, analgesic, antipyretic actions as well as the ulcerogenic properties of these aspirin-like compounds. An alternative metabolic pathway of arachidonic acid, via the lipoxygenase system, can be inhibited by an acetylenic analogue and a newer compound, phenidone. The unstable endoperoxide intermediates can be transformed by blood platelets into the pro-aggregating products, thromboxanes. This pathway can be selectively inhibited by a variety of experimental compounds. Prostacyclin, a potent vasodilator and inhibitor of platelet aggregation is the major product of endoperoxide transformation in blood vessels. Its formation can be inhibited by lipid peroxides. Selective actions on one or more steps in arachidonic acid metabolism can lead to a different profile of the products subsequently generated. Such a diversion of biosynthetic pathways may be an underlying mechanism in certain pathological conditions, perhaps even in dysmenorrhea.
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001095:Arachidonic Acids / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D011464:Epoprostenol / Q000378:metabolism; D006801:Humans; D016859:Lipoxygenase Inhibitors; D010740:Phospholipases / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D013929:Thromboxane B2; D013928:Thromboxane A2; D011464:Epoprostenol; D010740:Phospholipases