Antisecretory effect of imidazole and its derivatives in an isolated gastric mucosa preparation and an anesthetized young chicken preparation; comparison with a histamine H2-receptor antagonist.

We invesigated the influences of imidazole on the basal and the secretagogue-stimulated gastric acid secretion in isolated bullfrog gastric mucosa preparations and in anesthetized young chickens. Imidazoles (1 x 10(-4) g/ml) readily depressed the basal acid secretion in gastric mucosa in vitro. The inhibitory effect of imidazole was diminished considerably after washing out of the drug. The maximum acid secretion elicited by tetragastrin or bethanechol was completely antagonized by imidazole (1 x 10(-4) g/ml). The stimulatory action of histamine or dibutyryl cyclic AMP was also remarkably depressed in the presence of imidazole (3 x 10(-4) g/ml). after dibenamine pretreatment (5 x 10(-5) g/ml) for 60 min, the isolated gastric mucosa preparation became refractory to tetragastrin, bethanechol and histamine, but responded to dibutyryl cyclic AMP. Imidazole protected the histamine sensitivity against dibenamine blockade in the concentration of 5 x 10(-4) g/ml. In anesthetized young chickens, imidazole (200 mg/kg, s.c.) depressed tetragastrin- and histamine-stimulated gastric acid secretion. The effects of the imidazole derivatives and several antagonists (metiamide, atropine, diphenhydramine, acetazolamide and 2,4-dinitrophenol) on acid production were compared with that of imidazole. From these results, it is concluded that imidazole has a potent antisecretory effect on the basal and the secretagogue-stimulated acid secretion.

Dibenamine blockade on gastric acid secretion in vitro and its protection by histamine antagonists.

Experiments to protect the histamine receptor against dibenamine blockade were carried out to elucidate the pharmacological characteristics of the H2-histamine receptor system for gastric acid secretion in isolated bullfrog gastric mucosa. Dibenamine alone (5 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml) irreversibly blocked both basal and histamine-stimulated acid secretion. However, when the preparation was treated with dibenamine in combination with histamine (1 times 10-minus 5 g/ml), the acid secretory response to histamine was restored after washing out dibenamine. Burimamide, an H2-receptor antagonist, also protected the histamine sensitivity against dibenamine blockade in the concentration of 1 times 10-minus 4 g/ml. Diphenhydramine and pyribenzamine were also protected with histamine receptor against dibenamine blockade. The acid secretion induced by the action of histamine on the diphenhydramine-protected receptor was antagonized by diphenhydramine as well as burimamide.