Pharmacological characteristics of DQ-2511 as a prokinetic agent

• Published in: Archives internationales de pharmacodynamie et de thérapie Vol. 330; no. 3; p. 332
• Main Authors: Hatanaka, S, Hosokami, T, Kawarabayashi, K, Iseri, M, Tsubokura, K, Furuhama, K
• Format: Journal Article
• Language: English
• Published: Belgium 01.11.1995
• Subjects: Administration, Oral; Analysis of Variance; Animals; Anti-Ulcer Agents - blood; Anti-Ulcer Agents - pharmacology; Benzamides - administration & dosage; Benzamides - blood; Benzamides - pharmacology; Benzamides - therapeutic use; Calcitonin Gene-Related Peptide - metabolism; Calcitonin Gene-Related Peptide - toxicity; Cisapride; Cisplatin - toxicity; Copper Sulfate - toxicity; Dogs; Dopamine - metabolism; Dopamine - toxicity; Female; Gastric Emptying - drug effects; Injections, Intraperitoneal; Male; Mice; Muscarine - metabolism; Muscarine - toxicity; Nicotine - metabolism; Nicotine - toxicity; Piperidines - administration & dosage; Piperidines - pharmacology; Piperidines - therapeutic use; Radioligand Assay; Sincalide - metabolism; Sincalide - toxicity; Structure-Activity Relationship; Vomiting - drug therapy
• ISSN: 0003-9780

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.