Alpha 2-adrenoceptor-mediated inhibition of gastric acid secretion by medetomidine is efficiently antagonized by atipamezole in rats.

The effect of a novel highly selective alpha 2-adrenoceptor agonist, medetomidine (4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole), was studied on gastric secretion in conscious and anaesthetized rats. Medetomidine (3-30 micrograms/kg s.c.) inhibited basal gastric acid and fluid output in conscious rats in a dose-dependent manner, while in anaesthetized rats no effect was observed when administered i.v. at the doses of 1-1000 micrograms/kg. Furthermore, medetomidine did not modify gastric acid output stimulated by infusion of histamine i.v. in anaesthetized rats, suggesting also that a medetomidine-induced change in gastric secretion does not involve any action on histamine H2-receptors. Furthermore, evidence was given indicating that alpha 2-adrenoceptors mediate the antisecretory action of medetomidine, since a low dose (0.1 mg/kg s.c., -30 min) of a selective alpha 2-adrenoceptor antagonist, atipamezole [MPV 1248, 4-(2-ethyl-2,3-dihydro-1H-inden-2-yl)-1H-imidazole] efficiently antagonized the effects of medetomidine (30 micrograms/kg s.c.) in conscious rats. In summary, medetomidine inhibits gastric secretion in the rat via alpha 2-adrenoceptor activation, the antisecretory action being blocked by atipamezole. Probably due to its high specificity for alpha 2-adrenoceptors, medetomidine did not show a stimulatory effect on gastric acid secretion in anaesthetized rats.