Pharmacology of JB-9315, a new selective histamine H2-receptor antagonist.

Abstract 1. 1. The histamine H 2 -receptor antagonistic activity and antisecretory and antiulcer effects of JB-9315 were studied in comparison with the standard H 2 blocker ranitidine. 2. 2. In vitro , JB-9315 is a competitive antagonist of histamine H 2 receptors in the isolated, spontaneously beating guinea-pig right atrium, with a pA 2 value of 7.30 relative to a value of 7.36 for ranitidine. JB-9315 was specific for the histamine H 2 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. 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 pylorusligated rat after intraperitoneal administration, total acid output over 4 h was inhibited by JB-9315 with an ID 50 of 32.8 mg/kg, confirming its H 2 -receptor antagonist properties. 4. 4. JB-9315 showed antiulcer activity against cold stress plus indomethacin-induced lesions with an ID 50 of 6.8 mg/kg. 5. 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. 6. These results indicate that JB-9315 is a new antiulcer drug that exerts a cytoprotective effect in addition to its gastric antisecretory activity.