Pharmacological profiles of the new histamine H2-receptor antagonist N-ethyl-N'-[3-[3-(piperidinomethyl)phenoxy] propyl] urea.
The histamine H2-receptor antagonistic activity and antisecretory effects of KU-1257 (N-ethyl-N'-[3-[3-(piperidinomethyl) phenoxy]propyl]urea, CAS 120958-90-9) were studied. The Ki values of KU-1257, roxatidine acetate, famotidine and cimetidine for the inhibition of [3H]-tiotidine binding to guinea-pig cerebral cortex were 0.040, 0.13, 0.016 and 0.40 mumol/l, respectively. The KB values of KU-1257, roxatidine acetate, famotidine and cimetidine for the antagonism against histamine-induced positive chronotropic response of isolated guinea-pig right atrium were 0.041, 0.14, 0.031 and 0.51 mumol/l, respectively. In pylorus-ligated rats, KU-1257, roxatidine acetate and famotidine inhibited gastric acid secretion with respective intraduodenal ID50 values of 12.3, 18.5 and 0.45 mg/kg. In dogs with Heidenhain pouch, the ID50 values of KU-1257 for the inhibition of acid output stimulated by histamine, tetragastrin and meat meal were 0.08, 0.39 and 0.15 mg/kg p.o., respectively. KU-1257 was 2-3 times more potent than roxatidine acetate regardless of secretagogues and twice less than famotidine in meat meal stimulation. These results indicate that KU-1257 is a potent and competitive histamine H2-receptor antagonist.
Sekiguchi
H
H
Central Research Laboratories, Kyorin Pharmaceutical Co., Ltd., Tochigi, Japan.
Hamada
K
K
Kobayashi
F
F
Taga
F
F
Uchida
H
H
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002927:Cimetidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004285:Dogs; D015738:Famotidine / Q000494:pharmacology; D005502:Food; D005744:Gastric Acid / Q000378:metabolism; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011708:Pylorus / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013758:Tetragastrin / Q000494:pharmacology
D006635:Histamine H2 Antagonists; D010671:Phenylurea Compounds; D010880:Piperidines; D013758:Tetragastrin; C080362:KU 1257; D015738:Famotidine; D002927:Cimetidine; C023990:tiotidine; C053742:roxatidine acetate