Pharmacological characterization of a novel 5-HT4 receptor agonist, TS-951, in vitro.

The pharmacological effect of a novel selective 5-HT4 receptor agonist, TS-951 (N-[endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl]-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide) was investigated in vitro. TS-951 potently inhibited specific [3H]GR113808 binding both in guinea-pig striatum and in mouse brain. The affinity of TS-951 for the 5-HT4 receptor was higher than those of other agonists, 5-HT, cisapride, mosapride and renzapride. On the longitudinal muscle of the guinea-pig ileum, TS-951 caused a concentration-dependent increase in the amplitude of electrically induced submaximal twitch contractions. On the longitudinal muscle of the guinea-pig distal colon, TS-951 also caused concentration-dependent contractions. TS-951 is a high-affinity, selective and potent 5-HT4 receptor agonist. This compound therefore can be considered as a useful pharmacological tool for investigating 5-HT4 receptor-mediated events.