Pharmacological characteristics of DQ-2511 as a prokinetic agent.

Abstract

The pharmacological characteristics of DQ-2511, a substituted benzamide (3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl] amino-N-methylbenzamide), as a prokinetic agent were studied. Cholecystokinin-octapeptide, dopamine, and alpha-calcitonin gene-related peptide, all suppressed gastric emptying in mice. Reversal of the depressed emptying occurred when DQ-2511 was administered by the oral or intraperitoneal route. When the action of eight proposed metabolites of DQ-2511 on the mouse cholecystokinin-octapeptide model was investigated, the main metabolite in plasma, MA-2, showed no effect, although two minor metabolites ameliorated or aggravated the delayed gastric emptying. This finding implies that DQ-2511, as the parent compound itself, exerts the ameliorative action. In dogs treated with cisplatin or copper sulfate, DQ-2511 had no antiemetic activity, as assessed by the number of vomiting episodes. The concern that the mechanism of action of DQ-2511 was blockade of receptors for cholecystokinin-octapeptide, dopamine, serotonin, alpha-calcitonin gene-related peptide, nicotine or muscarine, was resolved by results of radioligand binding studies showing the absence of a DQ-2511 binding to any of these receptor types. Evidence is accumulating that the mechanism of the prokinetic action of DQ-2511 involves the intrinsic and extrinsic autonomic innervation.

• Authors: S Hatanaka, T Hosokami, K Kawarabayashi, M Iseri, K Tsubokura, K Furuhama
• Journal: Archives internationales de pharmacodynamie et de therapie (Arch Int Pharmacodyn Ther) 1995 Nov-Dec Vol. 330 Issue 3 Pg. 332-44 ISSN: 0003-9780 [Print] Belgium
• PMID: 8836452 (Publication Type: Journal Article)

Chemical References

• Anti-Ulcer Agents
• Benzamides
• Piperidines
• ecabapide
• Nicotine
• Muscarine
• Calcitonin Gene-Related Peptide
• Copper Sulfate
• Sincalide
• Cisplatin
• Cisapride
• Dopamine

Topics

• Administration, Oral
• Analysis of Variance
• Animals
• Anti-Ulcer Agents (blood, pharmacology)
• Benzamides (administration & dosage, blood, pharmacology, therapeutic use)
• Calcitonin Gene-Related Peptide (metabolism, toxicity)
• Cisapride
• Cisplatin (toxicity)
• Copper Sulfate (toxicity)
• Dogs
• Dopamine (metabolism, toxicity)
• Female
• Gastric Emptying (drug effects)
• Injections, Intraperitoneal
• Male
• Mice
• Muscarine (metabolism, toxicity)
• Nicotine (metabolism, toxicity)
• Piperidines (administration & dosage, pharmacology, therapeutic use)
• Radioligand Assay
• Sincalide (metabolism, toxicity)
• Structure-Activity Relationship
• Vomiting (drug therapy)