Stimulatory effect of N-[4-[2-(dimethylamino)-ethoxy] benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803) on normal and delayed gastrointestinal propulsion.
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.
Iwanaga
Y
Y
Central Research Laboratories, Hokuriku Seiyaku, Co., Ltd., Fukui, Japan.
Miyashita
N
N
Mizutani
F
F
Morikawa
K
K
Kato
H
H
Ito
Y
Y
Itoh
Z
Z
D000082:Acetaminophen / Q000008:administration & dosage / Q000097:blood; D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D001593:Benzyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D020117:Cisapride; D004285:Dogs; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004415:Dyspepsia / Q000503:physiopathology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D001549:Benzamides; D001593:Benzyl Compounds; D010880:Piperidines; C064878:N-(4-(2-(dimethylamino)ethoxy)benzyl)-3,4-dimethoxybenzmide; D000082:Acetaminophen; D004294:Domperidone; D008787:Metoclopramide; D020117:Cisapride; D004298:Dopamine