RP 73870, a gastrin/cholecystokinin-B receptor antagonist with potent anti-ulcer activity in the rat.
RP 73870, the racemic potassium salt of (([N-(methoxy-3-phenyl)-N-(N-methyl-N-phenyl-carbamoylmethyl)- carbamoylmethyl]-3-ureido)-3-phenyl)-2-ethylsulfonate-(RS) is a potent, reversible antagonist of both gastrin and cholecystokinin-B receptors in guinea pig and rat tissues. This compound is a potent inhibitor of pentagastrin-stimulated gastric acid secretion in the perfused rat stomach. RP 73870 also inhibits basal gastric acid secretion in the rat, although at doses higher than that required for inhibition of pentagastrin-stimulated gastric acid secretion. RP 73870 is a potent inhibitor of aspirin-induced gastric damage in the rat. In the prevention of aspirin-induced gastric damage, RP 73870, given p.o., was 10-fold less potent than when given i.v. RP 73870 was as potent as a H2 receptor antagonist or proton pump inhibitor in the prevention of cysteamine-induced duodenal ulcers in the rat. Relative to other gastrin/cholecystokinin-B antagonists, RP 73870 demonstrates greater affinity to gastrin binding sites, and possesses a unique spectrum of in vivo biological activities appropriate for an anti-ulcer indication.
Pendley
C E
CE
Department of General Pharmacology, Rhône-Poulenc Rorer Central Research, Collegeville, Pennsylvania, USA.
Fitzpatrick
L R
LR
Capolino
A J
AJ
Davis
M A
MA
Esterline
N J
NJ
Jakubowska
A
A
Bertrand
P
P
Guyon
C
C
Dubroeucq
M C
MC
Martin
G E
GE
D000818:Animals; D000897:Anti-Ulcer Agents / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D004381:Duodenal Ulcer / Q000517:prevention & control; D005753:Gastric Mucosa / Q000378:metabolism; D006168:Guinea Pigs; D010671:Phenylurea Compounds / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013276:Stomach Ulcer / Q000517:prevention & control
D000897:Anti-Ulcer Agents; D010671:Phenylurea Compounds; C094193:RP 73870; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin