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Stimulatory effect of N-[4-[2-(dimethylamino)-ethoxy] benzyl]-3,4-dimethoxybenzamide hydrochloride (HSR-803) on normal and delayed gastrointestinal propulsion.

Abstract
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.
AuthorsY Iwanaga, N Miyashita, F Mizutani, K Morikawa, H Kato, Y Ito, Z Itoh
JournalJapanese journal of pharmacology (Jpn J Pharmacol) Vol. 56 Issue 3 Pg. 261-9 (Jul 1991) ISSN: 0021-5198 [Print] Japan
PMID1895573 (Publication Type: Journal Article)
Chemical References
  • Benzamides
  • Benzyl Compounds
  • Piperidines
  • N-(4-(2-(dimethylamino)ethoxy)benzyl)-3,4-dimethoxybenzmide
  • Acetaminophen
  • Domperidone
  • Metoclopramide
  • Cisapride
  • Dopamine
Topics
  • Acetaminophen (administration & dosage, blood)
  • Administration, Oral
  • Animals
  • Benzamides (administration & dosage, pharmacology)
  • Benzyl Compounds (administration & dosage, pharmacology)
  • Cisapride
  • Dogs
  • Domperidone (administration & dosage, pharmacology)
  • Dopamine (pharmacology)
  • Dyspepsia (physiopathology)
  • Female
  • Gastric Emptying (drug effects)
  • Gastrointestinal Motility (drug effects)
  • Male
  • Metoclopramide (administration & dosage, pharmacology)
  • Mice
  • Piperidines (administration & dosage, pharmacology)
  • Rats
  • Rats, Inbred Strains
  • Stimulation, Chemical

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