1 The effects of the new H2-receptor antagonist famotidine, administered orally, on gastric secretion and emptying as well as on experimentally-induced gastric and duodenal ulcers were studied in the rat. Ranitidine was used as a reference compound.2 Both compounds inhibited acid secretion in a dose-dependent manner. Calculated ED_, values were 0.80 and 6.84mg kg' for famotidine and ranitidine, respectively. However, the duration of the antisecretory action was the same for both drugs. 3 The effect of the two drugs, administered at equiactive antisecretory doses, on gastric emptying was different. Ranitidine significantly accelerated the emptying rate whereas famotidine had no effect. 4 Famotidine reduced, in a dose-dependent manner, ulcer incidence in stomachs of dimaprit-treated rats and in duodena of cysteamine-treated animals with a potency respectively 2 and 7 times higher than that of ranitidine. 5 Famotidine is therefore an effective antisecretory and untiulcer'compound. Its potency, but not its efficacy, is higher than that of ranitidine. Moreover, the duration of the antisecretory action is virtually the same for both drugs.

Guinea‐pig duodenum contracted by histamine or by acetylcholine was relaxed dose‐dependently by a series of H2‐receptor selective agonists namely dimaprit, impromidine, clonidine and tolazoline. This relaxation was not neurally mediated since it was not modified by tetrodotoxin nor was it exerted through sympathetic receptors because it was not modified by pretreatment with propranolol or phentolamine. Apparently it was connected with the H2‐receptor stimulation more than to peculiarities of the single compounds. However a series of H2‐blockers (metiamide, cimetidine, ranitidine or oxmetidine) were unable to counteract the effect of the H2‐agonists or the relaxant effect of histamine in the presence of chlorpheniramine. This peculiar situation seems to indicate the existence of anomalous H2‐receptors, susceptible to the action of the agonists but not to that of the antagonists.

1 Histamine and a series of compounds acting selectively on H1-and H2-receptors were tested on the isolated oestrous uterus of the rat. 2 Histamine had a dose-dependent inhibitory effect on the contractions elicited by acetylcholine. This action was unaffected by H1-blockers but was competitively inhibited by H2-blockers. The H1-selective agonist, 2-(2-aminoethyl)thiazole was ineffective at doses 100 times greater than those of histamine. Conversely, all the H2-agonists showed activity in the order of potency: N'-methylhistamine > histamine > N'-N'-dimethylhistamine > 5-methylhistamine > 5-methyl-N'-methylhistamine. Among the non-imidazole compounds, dimaprit had an activity identical to that of histamine, but all the dimaprit-like compounds showed negligible activity. 3 The data obtained suggest that in the rat uterus, (a) the activation of H2-receptors is responsible for the inhibitory effect of histamine and its analogues; (b) the integrity of the histamine molecule seems to be less crucial than that of the dimaprit molecule for the maintenance of the H2-activity, since changes in its structure modify but do not abolish the biological activity as they do in the case of dimaprit; (c) the order of activity of the various H2-receptor agonists is different from that observed in other tissues.