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Effect of BMY‐25368, a potent and long‐acting histamine H 2 ‐receptor antagonist, on gastric secretion and aspirin‐induced gastric lesions in the dog
Author(s) -
CAVANAGH R. L.,
BUYNISKI J. P.
Publication year - 1989
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.1989.tb00217.x
Subject(s) - histamine , medicine , gastric secretion , aspirin , antagonist , secretion , histamine h2 receptor , pharmacology , receptor antagonist , gastric acid , gastroenterology , endocrinology , receptor
SUMMARY BMY‐25368, 1‐amino‐2‐[3‐(3‐piperidinomethylphenoxy) propylamino]‐1‐cyclobutene‐3,4‐dione, a new histamine H 2 ‐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.