To estimate the effect of a new gastroprokinetic agent, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803), on non-
ulcer dyspepsia, the influence of
HSR-803 on gastrointestinal propulsion was assayed in dogs, rats and mice in comparison with some gastroprokinetic agents.
HSR-803 (30 mg/kg, p.o.) significantly enhanced gastric emptying in dogs, and it significantly improved the delayed gastric emptying induced by
dopamine (0.4 mg/kg, i.p.) and
morphine (1 mg/kg, s.c.) in rats.
Metoclopramide (30 mg/kg, p.o.) also significantly restored the
dopamine-induced delay, but at a dose of 10 mg/kg, p.o., it enhanced the
morphine-induced delay in gastric emptying in rats.
HSR-803 (10-100 mg/kg, p.o.) increased small intestinal transit in mice in a dose-dependent manner, and the effect was abolished by
atropine (0.3 mg/kg, i.p.).
Metoclopramide also increased small intestinal transit, but
domperidone and
cisapride had no effect. In delayed small intestinal transit in mice,
HSR-803 (10-100 mg/kg, p.o.) improved the
morphine (0.3 mg/kg, s.c.)-induced delay in a dose-dependent manner. In conclusion, because of the promotion of normal and delayed gastrointestinal propulsion,
HSR-803 seems to be a promising gastroprokinetic agent for the treatment of non-
ulcer dyspepsia. The action of
HSR-803 is likely to be exerted through
cholinergic stimulation.