A relatively specific and quantitative assay for histamine H2-receptor blocking activity by determination of inhibition of histamine-induced gastric acid secretion in the rat.
A relatively specific method for the quantitative assay of histamine H2-receptor antagonists has been developed. The method is based on the antagonism of the histamine-induced, and the spontaneous, gastric acid secretion in the stomach-perfused, urethane-anesthetized acute rat. For the induced gastric acid secretion, the animal received two consecutive equal injections of histamine (2 mg/kg, intrajugularly), the second 1.7 h after the termination of the first histamine-induced acid hypersecretion. Atropine (5 mg/kg), chlorisondamine (2 mg/kg), imipramine (10 mg/kg) and tripelennamine (5 mg/kg), administered i.p., failed to inhibit the histamine-induced, or the spontaneous, gastric acid secretion. Metiamide inhibited the histamine-induced acid secretion (ED50 1.85 mg/kg, i.p.) and the spontaneous acid secretion (10 mg/kg, i.p.). These results suggest that in the rat model employed in this study, histamine and H2-receptors play a very important role in the regulation of the gastric acid secretion. Other mechanisms involving cholinergic tone, biogenic amine uptake and histamine H1-receptors do not seem to intervene.
D000818:Animals; D005750:Gastric Juice / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D008722:Methods; D051381:Rats; D013997:Time Factors
D006635:Histamine H2 Antagonists; D006632:Histamine