In vivo and in vitro effects of CM 57755, a new gastric antisecretory agent acting on histamine H2 receptors.
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.
D000818:Animals; D000897:Anti-Ulcer Agents; D002415:Cats; D002927:Cimetidine / Q000494:pharmacology; D017259:Dimaprit; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007082:Ileum; D066298:In Vitro Techniques; D009130:Muscle, Smooth / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013890:Thiourea / Q000037:antagonists & inhibitors
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D009536:Niacinamide; D002927:Cimetidine; D011899:Ranitidine; C041784:ramixotidine; D013890:Thiourea; D017259:Dimaprit