Stimulatory Effect of N-[4-[2-(Dimethylamino)-ethoxy]benzyl]-3, 4-Dimethoxybenzamide Hydrochloride (HSR-803) on Normal and Delayed Gastrointestinal Propulsion

• Published in: The Japanese Journal of Pharmacology Vol. 56; no. 3; pp. 261 - 269
• Main Authors: Iwanaga, Yuji, Miyashita, Naoshi, Mizutani, Fujie, Morikawa, Kouji, Kato, Hideo, Ito, Yasuo, Itoh, Zen
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1991
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1254/jjp.56.261

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.