Antiulcerogenic effect of a pyrido-benzodiazepine derivative (L-S 519) on experimental ulcers

Effects of a tricyclic, pyrido-benzodiazepnie derivative, 5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-6][1,4]-benzodiazepin-6-one-dihydrochloride (L-S 519) on experimental ulcers produced by pylorus ligation, cold restraint-stress, and reserpine, and on gastric secretions stimulated by histamine, tetragastrin and carbachol in rats were studied. L-S 519 was half as potent as atropine in preventing these experimental acute ulcers and in decreasing the spontaneous gastric secretion. This compound inhibited to various degrees the gastric secretion stimulated by histamine, tetragastrin and carbachol in acute fistula rats. On the other hand, the antimuscarinic effects of L-S 519 were much weaker than those of atropine in both in vivo and in vitro experiments. Furthermore, the antigastric secretory effect of L-S 519 was observed even in pylorus-ligated, vagotomized rats. By contrast, the effect of L-S 519 was reduced by pretreatment with 6-hydroxydopamine. These results suggest that the adrenergic mechanisms, in addition to a weak antimuscarinic property, are involved in antisecretory and antiulcerogenic effects of L-S 519.