CP-66,948: an antisecretory histamine H2-receptor antagonist with mucosal protective properties.
CP-66,948 is a histamine H2-receptor antagonist with gastric antisecretory activity and mucosal protective properties. The affinity of CP-66,948 for the guinea pig atria histamine H2-receptor is 15 times greater than that of cimetidine and seven times greater than that of ranitidine. In vivo, the ED50 value for inhibition of gastric acid secretion in pylorus-ligated rats is 2 mg/kg intraduodenally, and in histamine or pentagastrin-stimulated Heidenhain pouch dogs the antisecretory ED50 values are 0.3 mg/kg per os and 1.0 mg/kg per os, respectively. CP-66,948 also inhibits ethanol-induced gastric hemorrhagic lesions in rats following either oral or systemic administration (ED50 values of 12 mg/kg per os and 6 mg/kg subcutaneously). In addition, the mucosal protective activity is independent of prostaglandin synthesis. CP-66,948 inhibits gastric acid secretion in man, and its mucosal protective activity may provide additional benefits in peptic ulcer therapy.
Hakkinen
J P
JP
Department of Metabolic Diseases, Central Research Division, Pfizer Inc., Groton, CT 06340.
Holt
W F
WF
Goddard
C J
CJ
Oates
P J
PJ
Murphy
W R
WR
Maciejko
J J
JJ
Reiter
L A
LA
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000473:pathology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
D007093:Imidazoles; D013844:Thiazoles; C072015:CP-66,948; D000431:Ethanol; D002927:Cimetidine; D006632:Histamine; D011899:Ranitidine; D010418:Pentagastrin; D007213:Indomethacin