Benzimidazolone derivatives act as 5-HT4 receptor ligands in rat oesophagus.

Three benzimidazolone derivatives have been evaluated in the tunica muscularis mucosae preparation of the rat oesophagus for activity at the 5-HT4 receptor. BIMU 1 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]oct-3-yl)-2,3-dihydro-3-ethyl-2-ox o- 1H-benzimidazole-1-carboxamide HCl) and BIMU 8 (endo-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)eth yl- 2-oxo-1H-benzimidazole-1-carboxamide HCl) acted as potent but partial agonists relative to 5-HT whereas DAU 6215 (N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)2,3-dihydro-2-oxo-1H- benzimidazole-1-carboxamide HCl) behaved as a competitive antagonist with a pA2 of 6.5. The pEC50 values for BIMU 1 and BIMU 8 were 8.0 and 7.9, respectively, compared with 8.2 for 5-HT. Intrinsic activity values were 0.7 and 0.9, respectively. BIMU 1 and BIMU 8 are the most potent synthetic agonists so far tested in rat oesophagus, and DAU 6215 exhibits an equivalent affinity to ICS 205 930 at the 5-HT4 receptor.