Effect of the novel histamine H2-antagonist 5,6-dimethyl-2-[4-[3-(1- piperidinomethyl)phenoxy]-(z)-2-butenylamino]-4(1H)-pyrimidine dihydrochloride on histamine-induced gastric acid secretion in Heidenhain pouch dogs.
Effects of IGN-2098 (5,6-dimethyl-2-[4-[3-(1-piperidinomethyl)phenoxy]- (z)-2-butenylamino]-4(1H)-pyrimidone dihydrochloride, CAS 126869-04-3) a novel histamine H2-antagonist, on histamine-induced gastric acid secretion were investigated in Heidenhain pouch dogs in comparison with those of famotidine, roxatidine acetate HCl and cimetidine. Orally administered IGN-2098 (0.03-1.0 mg/kg), famotidine (0.01-0.3 mg/kg), roxatidine acetate HCl (0.1-1.0 mg/kg) and cimetidine (0.3-3.0 mg/kg) showed dose-dependent inhibition on histamine-induced gastric acid secretion, and ED50 values of IGN-2098, famotidine, roxatidine acetate HCl and cimetidine were 0.077, 0.024, 0.200 and 0.585 mg/kg, respectively. IGN-2098 was effective even at 6 h after administration and ED50 value was 0.315 mg/kg. IGN-2098 was effective also by intravenous route. The inhibitory effect of IGN-2098 on histamine-induced gastric secretion was not affected by the repeated administration of IGN-2098 (1 mg/kg b.i.d. for 14 days). These results show that IGN-2098 is a potent and long acting antisecretory agent and is a useful antisecretory drug for the treatment of peptic ulcer disease.
Uchida
M
M
Pharmacological Laboratory, Grelan Pharmaceutical Co., Ltd., Tokyo, Japan.
Ohba
S
S
Ikarashi
Y
Y
Misaki
N
N
Kawano
O
O
D000284:Administration, Oral; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015738:Famotidine / Q000494:pharmacology; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D010880:Piperidines; D011744:Pyrimidinones; C076167:IGN 2098; D015738:Famotidine; D002927:Cimetidine; D006632:Histamine; C053742:roxatidine acetate