thiourea and ramixotidine

The antisecretory effects of CM 57755, a new histamine-H2 receptor antagonist, have been compared with those of cimetidine on gastric acid secretion induced by intravenous infusions of dimaprit or pentagastrin into conscious cats with chronically implanted gastric fistulae. Intravenous infusion of CM 57755 induced a parallel shift to the right of the dimaprit dose-response curve. The potency of CM 57755 was comparable with that of cimetidine as shown by similar doses causing a 5-fold displacement to the right of the dimaprit dose-response curve (4.9 mumol kg-1 h-1 for CM 57755 and 4.7 mumol kg-1 h-1 for cimetidine). Unlike that with dimaprit, the acid secretion stimulated by increasing doses of pentagastrin was inhibited by CM 57755 with depression of the maximal effect, indicating non-competitive antagonism. In a second series of experiments the time course of the anti-secretory action of intragastrically administered CM 57755 was studied from the gastric acid secretion induced by constant infusion of dimaprit. At equieffective doses, CM 57755 caused more sustained inhibition than cimetidine.

Topics: Animals; Cats; Cimetidine; Dimaprit; Gastric Acid; Histamine H2 Antagonists; Kinetics; Male; Niacinamide; Pentagastrin; Thiourea

The pharmacological activity of CM 57755, a new gastric antisecretory compound of the anti-H2 type, was studied in certain in vivo and in vitro preparations. In stomach-lumen perfused rats it proved to be, on a molar basis, half as active as cimetidine and 1/13 as active as ranitidine in inhibiting histamine-induced gastric acid secretion. On the other hand, CM 57755 administered to conscious gastric-fistula cats, either i.v. or intragastrically, depressed the hypersecretory plateau evoked by constant infusion of dimaprit with a potency comparable to that of cimetidine. In this preparation, the inhibition at equieffective doses of antagonists was more sustained for CM 57755 than for cimetidine and ranitidine. Applied to isolated guinea-pig right atria and gastric mucosa, CM 57755 competitively antagonized histamine effects (respective pA2's: 5.4 and 5.9) but was less potent than expected from its in vivo antisecretory activity. Bioavailability and/or biotransformation are the factors most likely to account for the differences observed between species, and between in vivo and in vitro studies for this long-acting antisecretory agent.

Topics: Animals; Anti-Ulcer Agents; Cats; Cimetidine; Dimaprit; Female; Gastric Acid; Gastric Mucosa; Guinea Pigs; Heart Rate; Histamine H2 Antagonists; Ileum; In Vitro Techniques; Muscle, Smooth; Niacinamide; Ranitidine; Rats; Rats, Inbred Strains; Thiourea