[Antiulcerogenic action of 7-chloro-1-cyclopropylmethyl-1,3-dihydro-5-(2-fluorophenyl)-2H-1,4-benzodiazepin-2-one (KB-509), a new benzodiazepine derivative].
Effects of KB-509, a new derivative of benzodiazepines and expected to be classified as an antianxiety drug, were studied on the experimental stress ulcers and serum 11-hydroxycorticosterone (11-OHCS) in mice. Firstly, we looked for a stress procedure under which diazepam would show antiulcerogenic effects at a lower dose than those required for a muscle relaxant effect in this species. We found that diazepam possessed a strong antiulcerogenic activity under the stress procedure (26 degrees C, 5 hr restraint and water immersion). KB-509 had a potent protective effect on the erosions induced by the present mild stress method at a considerably low dose (ED50: 0.36 mg/kg, p.o.) and the potency was about 3 and 9 times greater than that of diazepam and atropine sulfate, respectively. KB-509 did not affect indomethacin-induced gastric erosions and thermal ulcers, as did diazepam. KB-509 and diazepam depressed stress-induced increase of serum 11-OHCS in mice, but not at the low doses required for antiulcerogenic effects. In conclusion, the results in this study suggest that the stress method described may be used to evaluate the antianxiety effect of benzodiazepines, especially in mice, and that KB-509 is superior to both diazepam and atropine in antiulcerogenic activity.
D015062:11-Hydroxycorticosteroids / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology / Q000627:therapeutic use*; D001570:Benzodiazepinones / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D006358:Hot Temperature; D007213:Indomethacin; D008297:Male; D051379:Mice; D013276:Stomach Ulcer / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D013312:Stress, Physiological
D015062:11-Hydroxycorticosteroids; D000927:Anticonvulsants; D001570:Benzodiazepinones; C029163:flutoprazepam; D007213:Indomethacin