piperidines and ecabapide

We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)- ethyl]carbamoyl]methyl]amino-N-methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ-2511 (3-10 mg kg-1) caused similar significant improvements to delays in gastric emptying of semi-solid meals evoked by cholecystokinin-octapeptide (CCK8: 5 micrograms kg-1, i.v.) in monkeys, to that with cisapride (3 mg kg-1). A 2-week oral treatment of unilaterally vagotomized rats with DQ-2511 (1-10 mg kg-1) lessened delays in gastric emptying, whereas cisapride (0.3-10 mg kg-1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 micrograms kg-1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ-2511 (6-60 micrograms kg-1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric emptying may differ from that of cisapride.

Topics: Afferent Pathways; Analysis of Variance; Animals; Anti-Ulcer Agents; Benzamides; Cisapride; Female; Gastric Emptying; Gastrointestinal Motility; Male; Muscle, Smooth; Nerve Fibers; Piperidines; Rats; Rats, Sprague-Dawley; Saimiri; Sincalide; Stomach; Vagotomy; Vagus Nerve