Effect of BMY-25368, a potent and long-acting histamine H2-receptor antagonist, on gastric secretion and aspirin-induced gastric lesions in the dog

BMY-25368, 1-amino-2-[3-(3-piperidinomethylphenoxy) propylamino]-1-cyclobutene-3,4-dione, a new histamine H2-receptor antagonist, has been compared to ranitidine as an inhibitor of gastric acid secretion in the Heidenhain pouch dog. Intravenous infusion of BMY-25368 antagonized histamine-stimulated gastric secretion in a competitive manner. BMY-25368 also antagonized gastric secretion stimulated by pentagastrin, bethanechol and food. When compared to ranitidine in histamine-stimulated dogs, BMY-25368 was nine times more potent after bolus intravenous administration. Oral potency relative to ranitidine and ranged from 2.8 to 4.4, depending on the secretagogue used. BMY-25368 also exhibited a significantly longer duration of action than ranitidine. Thus, its potency relative to ranitidine after oral administration, in histamine-stimulated dogs, increased from 3.2 to 28 when determined 1-3 and 10-12 h post dose, respectively. BMY-25368 administered orally also antagonized aspirin-induced gastric lesions in the dog and was nine times more potent than ranitidine in this respect.