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-flammatory 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 non-steroidal anti-flammatory drugs, they fail to inhibit the acute anti-flammatory and anti-nociceptive effects of these drugs. They are anti-flammatory 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 inhibition per 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.