Antispasmodic and visceral analgesic effects of new 5-HT 3 receptor antagonist emetazol in experiment

Abstract

The ability of emetazol (RU-1276, l-piperiduiopropil-2-(4-fluorophenyl)imidazo[l,2-a]benzimidazole dihydrochloride) to reduce the serotonin-induced ileum spasm on the Guinea pig model in vitro and to decrease pain sensitivity on the model of abdominal pain in dogs was investigated. Emetazol has a potent antispasmodic action comparable with that of ondansetron and 2.5 times greater than that of metoclopramide (p < 0.05), as well as a significant visceral analgesic effect manifested by the drug-induced attenuation of visceromotor and cardiovascular responses of awake dogs to noxious rectal distension(by 46.7 ± 6.8% and 29.4 ± 7.9%, respectively, p < 0.0001). These results show that emetazol has a high potential as a biologically active substance for the treatment of intestinal hyperkinesia and hypersensitivity in irritable bowel syndrome and is worth of carrying out relevant preclinical trials.