Effect of alpha2 agonists clonidine, guanfacine and B-HT 920 on gastric acid secretion and ulcers in rats.

The antisecretory and gastric ulcer protective effects of clonidine were studied in four different experimental models in rats. The effects were compared with two other alpha2 agonists guanfacine and B-HT 920 at equimolar dose basis. Clonidine (0.05-1 mg/kg) produced antisecretory effect at all doses but the maximum effect was noticed at 0.1 mg/kg. Its ulcer protective effect against immobilization stress-induced ulcers was comparable to diazepam but was not completely reversed by Ro 15-1788, a benzodiazepine antagonist. Clonidine showed an inhibitory response on basal gastric secretion in the continuous perfusion technique. It also reversed the effects of systemically administered indomethacin on gastric acid secretion and ulcers. Guanfacine produced a biphasic response on basal gastric secretion. The excitatory response was prolonged by bilateral vagotomy and inhibited by cimetidine treatment. Tachyphylaxis was observed in its excitatory response. It also showed inhibitory effects on pyloric ligation and indomethacin-induced gastric acid secretion. While B-HT 920 shared the antisecretory effects of clonidine and guanfacine in pyloric ligation, stress and drug-induced gastric secretion and ulcer protection, it had little or no effect on basal secretion in the continuous perfusion of the stomach. Since yohimbine was able to reverse the inhibitory effects of alpha2 agonists, the antisecretory effect of these agents predominantly involved the action on alpha2 adrenoceptors.