Anomalous biological effects of salicylates and prostaglandins

While some salicylates (salicyclic acid and salicylaldehyde, especially) are as potent as aspirin as acute, orally-active anti-inflammatory drugs in the rat, they are either inactive or far less potent as PG synthesis inhibitors when added directly to isolated platelets or when given orally.Although PGE₁ and PGE₂ produce anti-ulcerogenic effects when given to rats in the presence of selected nonsteroidal anti-inflammatory drugs, they fail to inhibit the acute anti-inflammatory and anti-nociceptive effects of these drugs. They are anti-inflammatory and anti-nociceptive under certain experimental conditions. PGE₁ and PGE₂ can also behave as hypothermic agents when given subcutaneously. Related studies, using PG synthesis stimulators in vivo and in vitro (substituted phenylureas), also cause anti-nociception and hypothermia.All of these indirect studies, when taken together, infer that PG synthesis inhibitionper se fails to explain, entirely, the pharmacologic effects of non-steroidal anti-inflammatory drugs. They also suggest that the precise role of certain PGs in toxicopharmacology is far from simple and straightforward.