| AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties. | |
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MedLine Citation:
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PMID: 2533479 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The gastrokinetic effects of AS-4370, 4-amino-5-chloro-2-ethoxy-N-([4-(4-fluorobenzyl)-2-morpholinyl] methyl) benzamide citrate, were compared with those of metoclopramide in experimental animals. In rats, AS-4370 increased the gastric emptying of a semi-solid meal and of resin pellets at dose ranges of 0.03-30 mg/kg and 1-10 mg/kg p.o., respectively. The minimal effective doses were 3-10 times lower than those of metoclopramide. Gastric emptying, delayed by gastroduodenal surgical intervention, was improved with AS-4370 (0.3-3 mg/kg p.o.). In conscious dogs with strain gauges implanted, AS-4370 (0.5 and 1.0 mg/kg i.v.) enhanced antral and duodenal motility without affecting ileal and colonic motility, indicating a selective enhancing effect on upper gastrointestinal motility. AS-4370 (10(-7) - 3 x 10(-5) M) increased electrically evoked, cholinergically mediated contractions in isolated guinea-pig ileum. AS-4370 (3 mg/kg i.v.) was without effect on gastric acid secretion in anesthetized rats. Unlike metoclopramide, AS-4370 neither depressed the active avoidance response in mice nor the food-reinforced lever pressing response in rats, even at 100 mg/kg p.o. Moreover, AS-4370 (10(-4) M) showed no affinity for D2, alpha 1, alpha 2, 5-HT1 and 5-HT2 binding sites in rat brain synaptic membranes. These results suggest that AS-4370 is a new and potent gastrokinetic agent that lacks dopamine D2 receptor antagonist properties. |
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Authors:
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N Yoshida; H Omoya; M Oka; K Furukawa; T Ito; T Karasawa |
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Publication Detail:
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Type: Comparative Study; Journal Article |
Journal Detail:
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Title: Archives internationales de pharmacodynamie et de thérapie Volume: 300 ISSN: 0003-9780 ISO Abbreviation: Arch Int Pharmacodyn Ther Publication Date: 1989 Jul-Aug |
Date Detail:
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Created Date: 1990-03-06 Completed Date: 1990-03-06 Revised Date: 2012-01-12 |
Medline Journal Info:
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Nlm Unique ID: 0405353 Medline TA: Arch Int Pharmacodyn Ther Country: BELGIUM |
Other Details:
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Languages: eng Pagination: 51-67 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Avoidance Learning / drug effects Benzamides / pharmacology* Conditioning, Operant / drug effects Dogs Electric Stimulation Gastric Acid / secretion Gastric Emptying / drug effects Gastrointestinal Agents / pharmacology* Gastrointestinal Motility / drug effects Guinea Pigs Ileum / drug effects Male Metoclopramide / pharmacology Mice Morpholines / pharmacology* Muscle, Smooth / drug effects Radioligand Assay Rats Receptors, Dopamine / drug effects* Receptors, Dopamine D2 |
| Chemical | |
Reg. No./Substance:
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0/Benzamides; 0/Gastrointestinal Agents; 0/Morpholines; 0/Receptors, Dopamine; 0/Receptors, Dopamine D2; 112885-42-4/mosapride; 364-62-5/Metoclopramide |
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