Furan H2-antagonist ranitidine inhibits pentagastrin-stimulated gastric secretion stronger than cimetidine.
In each of 7 healthy volunteers, the new furan H2-antagonist ranitidine (0.125, 0.25, 0.5, and 1.0 mg . kg-1 . hr-1) or the imidazole derivative cimetidine or normal saline were intravenously infused in the midhour of a 3-hr pentagastrin period (1.5 micrograms . kg-1 . hr-1 i.v.). With increasing doses of ranitidine, gastric acid secretion dropped dose dependently: 62, 78, 89, and 94%, respectively (P < 0.05 for all doses). A cimetidine dose of 0.82 mg . kg-1 . hr-1 (2.8 mumol . kg-1 . hr-1), equivalent to the highest ranitidine dose, led to a similar reduction of acid output (54%) as an eightfold smaller ranitidine dose. Apparently in human gastric mucosa, recognition of H2-receptors is not exclusively determined by the imidazole ring. Strong inhibitory efficacy of ranitidine was also reflected by the low calculated mean ID50 of 54 micrograms (0.15 mumol) . kg-1 . hr-1 and the IC50 of 36 ng/ml (0.1 microM). Acid inhibition by ranitidine involved both reduction in volume and acidity. The lowering effect on pepsin output was less pronounced though significant. Secretion of free N-acetylneuraminic acid and N-acetylneuraminic acid bound to glycoproteins did not change after H2-blocker administration indicating an unimpaired mucus secretion. In these short-term experiments, there were no obvious side effects or alterations in routine laboratory parameters including serum gastrin and prolactin attributable to either drug.
D000328:Adult; D000863:Antacids; D055598:Chemical Phenomena; D002621:Chemistry; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000008:administration & dosage / Q000494:pharmacology*; D005750:Gastric Juice / Q000378:metabolism*; D006635:Histamine H2 Antagonists / Q000008:administration & dosage* / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011899:Ranitidine; D013268:Stimulation, Chemical
D000863:Antacids; D005663:Furans; D006635:Histamine H2 Antagonists; D006728:Hormones; D002927:Cimetidine; D011899:Ranitidine; D010418:Pentagastrin