Effect of benzydamine, a topically administered NSAID onin vitro prostanoid synthesis by human and rat gastric mucosa and rat kidney, aorta and urinary bladder: Lack of effect on cyclooxygenase but potent inhibition of receptor-linked prostanoid synthesis

Abstract

Orally administered NSAIDs are notorious for their frequent and severe side-effects in the gastrointestinal tract and kidney, whereas topically administered NSAIDs may avoid these untoward effects. Since NSAID-induced side-effects are largely prostaglandin (PG)-mediated, the effects of the topically administered NSAID, benzydamine, onin vitro PGI2 and PGE2 synthesis by the rat and human gastric mucosa and rat kidney slices was investigated. The effect on receptor-linked PG synthesis in the isolated rat aorta (adrenergic) and urinary bladder (cholinergic) was also investigated since NSAIDs may disrupt mobilization of calcium therein. Benzydamine was a very weak inhibitor of spontaneous PGI2 and PGE2 synthesis by human and rat gastric mucosa and rat kidney. In contrast, benzydamine was a potent inhibitor of noradrenaline- and carbachol-stimulated (but not arachidonate- or trauma-stimulated) PGI2 synthesis. It is concluded that: a) benzydamine is unlikely to elicit cyclooxygenase-mediated side-effects on the gastrointestinal tract or kidney, b) the anti-inflammatory action of benzydamine is mediated by disruption of calcium linked to receptor-PG synthesis coupling, and c) calcium-dependent inflammatory processes may also be affected by benzydamine.