Pharmacological profile of etintidine, a new histamine H2-receptor antagonist.
Etintidine is a potent competitive antagonist of histamine H2-receptors. It is 4.6 and 2.2 times more potent than cimetidine in the isolated guinea pig atrium (pA2 = 7.18) and the isolated rabbit parietal cell (pA2 = 6.51), respectively. Etintidine is 2.0 (ED50 = 1.8 mg/kg, i.g.) times more potent than cimetidine at inhibiting betazole-stimulated total acid output in the chronic gastric fistula dog. In the 4 hr pylorus-ligated rat etintidine is a potent inhibitor of total acid output (ED50 = 22 mg/kg, i.d.), total pepsin output, and is well absorbed from the gastrointestinal tract. Additional pharmacological and biochemical studies indicate that etintidine displays minimal competition with appropriate ligands for the alpha 1, alpha 2, cholinergic and neuroleptic receptors in vitro, and has minimal effects on the immunological, autonomic and central nervous systems at doses much higher than antisecretory doses. While high doses of both cimetidine and etintidine increase serum prolactin levels in rats, the effect of etintidine is less than that of cimetidine. Similarly, the prolongation of hexobarbital-induced sleep time in rats is less than with cimetidine. These data indicate that etintidine may be potentially useful and safe in the treatment of peptic ulcer disease and may offer some advantages over cimetidine in terms of less potential for side effects.
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D003250:Constriction; D004285:Dogs; D005260:Female; D005750:Gastric Juice / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006386:Hemagglutination Tests; D006591:Hexobarbital / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010295:Parietal Cells, Gastric / Q000187:drug effects / Q000378:metabolism; D010434:Pepsin A / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011708:Pylorus; D011817:Rabbits; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects
D006635:Histamine H2 Antagonists; D007093:Imidazoles; D002927:Cimetidine; D006632:Histamine; D011388:Prolactin; C036616:etintidine; D006591:Hexobarbital; D010434:Pepsin A