Effects of SN-307, a Novel 5-HT3 Receptor Antagonist, on Rodential Gastrointestinal Motility

The effects of SN-307, selective and potent 5-HT3 receptor antagonist, on gastrintestinal motility were investigated using mouse, rat and guinea-pig models. Gastrointestinal transit of charcoal meal in mice was inhibited by pretreatment with SN-307, which was given orally and intravenously. In sham-operated or appendectomized mice, on the other hand, it was facilitated by pretreatment with SN-307, given intravenously. Gastric emptying in rats was enhanced by SN-307 at a low dose （0.01 mg/kg, i. v.） but was inhibited at a high dose （1.0 mg/kg, i. v.）. The spontaneous contractile activity of the isolated guinea-pig stomach was facilitated by SN-307 at a low dose but inhibited at a high dose. The muscle tone of the isolated stomach was increased by SN-307 at a low concentration （10-7M）, but decreased at a high concentration （10-5M）. The vagal stimulation-induced contraction of the isolated guinea-pig stomach was inhibited by 10-6M SN-307. From the above results, it seems likely that SN-307 causes dual effects in rodential gastrointestinal motility depending on the given doses of the drug.departmental bulletin pape