Pharmacological properties of the novel antimuscarinic agent 4-[2-(1,2-benzisoxazol-3-yl)-2-(hexahydro-1H-azepin-1-yl)a cetoxy]-1-et hyl-1- methylpiperidinium iodide.

Pharmacological properties of 4-[2-(1, 2-benzisoxazol-3-yl)-2-(hexahydro-1H-azepin-1-yl)acetoxy]-1- ethyl-1- methylpiperidinium iodide (SX-810) were investigated and the following results were obtained. 1. In isolated guinea-pig ileum, SX-810 showed a competitive antagonistic effect against acetylcholine with a pA2 value of 7.93. 2. SX-810 (10-50 mg/kg p.o. or 10-50 micrograms/kg i.v.) inhibited the gastroduodenal contractions induced by bethanechol and carbachol in anaesthetized rats. 3. SX-810 (10-100 mg/kg p.o.) inhibited spontaneous gastric motility in conscious rats and rabbits. 4. SX-810 (10-100 mg/kg p.o.) inhibited gastric secretion in pylorus-ligated rats. 5. SX-810 (20-200 mg/kg p.o. or 1-10 mg/kg s.c.) inhibited the ulceration induced by pylorus ligation or by exposure to restrained and water-immersed stress in rats. 6. When administered orally to rats, SX-810 had no mydriatic effect even at 3000 mg/kg, but subcutaneously administered SX-810 (0.5-10 mg/kg) exhibited such action. 7. When administered orally to rats, SX-810 (100-500 mg/kg) caused no significant inhibition of the salivation induced by pilocarpine, but subcutaneously administered SX-810 (0.5-10 mg/kg) exhibited an inhibition of the salivation. In rabbits, SX-810 (200-500 mg/kg p.o.) also caused no significant inhibition of the salivation except at an extremely high dose of 1000 mg/kg p.o. 8. SX-810 (100-500 mg/kg p.o.) caused no significant effect on urine and electrolyte excretion in rats. These results indicate that oral use of SX-810 exhibits marked spasmolytic and antiulcerative activities without exerting systemic antimuscarinic side effects.