Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.
1. The histamine H2-receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H2 blocker ranitidine. 2. In vitro, JB-9315 is a competitive antagonist of histamine H2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H2 receptor because, at high concentration, it did not affect histamine- or acetylcholine-induced contractions in guinea-pig isolated ileum or rat isolated duodenum, respectively. 3. JB-9315 dose dependently inhibited histamine-, pentagastrin- or carbachol-stimulated acid secretion and basal secretion in the perfused stomach preparation of the anesthetized rat. In the pylorus-ligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID50 of 32.8 mg/kg, confirming its H2-receptor antagonist properties. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID50 of 6.8 mg/kg. 5. JB-9315, 50 and 100 mg/kg, inhibited macroscopic gastric hemorrhagic lesions induced by ethanol. In contrast, ranitidine (50 mg/kg) failed to reduce these lesions. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.
Palacios
B
B
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Montero
M J
MJ
Sevilla
M A
MA
San Román
L
L
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000494:pharmacology*; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D003517:Cyclopentanes; D005663:Furans; D006635:Histamine H2 Antagonists; D006632:Histamine; D011899:Ranitidine; D002217:Carbachol; D010418:Pentagastrin; C111342:JB 9315