H2-receptor antagonist and gastric acid antisecretory properties of Wy-45,662.
Investigations were carried out to delineate the biological activity of Wy-45,662, a new H2-receptor antagonist. In the pylorus-ligated rat after intraduodenal administration, total acid output (TAO) over 4 hours was inhibited by Wy-45,662 with an ED50 of 0.3 mg/kg as compared to ranitidine (ED50 = 7 mg/kg) and cimetidine (ED50 = 12 mg/kg); i.v. or i.m. administration increased Wy-45,662's potency 10-fold. In dogs with innervated gastric pouches Wy-45,662 inhibited food-stimulated TAO with ED50's of 0.35 mg/kg (p.o.), 0.045 mg/kg (i.v.) and 0.065 mg/kg (i.m.); cimetidine (ED50 = 6 mg/kg p.o.) and ranitidine (ED50 = 1 mg/kg p.o.) were less potent. Wy-45,662 also inhibited pentagastrin- or histamine-stimulated acid secretion in the conscious fistula rat. In vitro, Wy-45,662 antagonized the histamine-stimulated a) positive chronotropism in guinea pig atria and b) [14C]aminopyrine uptake by rat gastric mucosal cells, confirming its H2-receptor antagonist properties.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists; D008297:Male; D050198:Phenoxypropanolamines; D011708:Pylorus / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D050198:Phenoxypropanolamines; D013844:Thiazoles; D005576:Colforsin; D003994:Bucladesine; C051466:Wy 45662