A NEW 5-HT3 RECEPTOR-LIGAND - II - STRUCTURE-ACTIVITY ANALYSIS OF 5-HT3 RECEPTOR AGONIST ACTION IN THE GUT

Several modified 2-piperazinyl benzoxazole derivatives, which exhibit an agonistic effect on gastrointestinal motility, were synthesized and their effects on the contraction of guinea-pig ileum were examined, T he quaternary piperazinyl benzoxazole structure has a restricted confo rmation and stereostructure compared to those of the other 5-HT3 recep tor agonists, serotonin and meta-chlorophenylbiguanide. The mutual pos itions of the aromatic ring, nitrogen atom and terminal amine are cons idered to form the pharmacophore of the 5-HT3 receptor agonist in the gut. In the serotonin-evoked reflex bradycardia [Bezold-Jarisch (B-J) reflex] inhibition test using rats the B-J reflex-inducing ratio was d ifferent for each synthesized compound. These results suggest that, in these 5-HT3 receptor agonists, the substituents of the benzoxazole ri ng influence the B-J reflex-inducing activity in rats.