Pharmacological characteristics of DQ-2511 as a prokinetic agent.
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.
Hatanaka
S
S
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co., Ltd', Tokyo, Japan.
Hosokami
T
T
Kawarabayashi
K
K
Iseri
M
M
Tsubokura
K
K
Furuhama
K
K
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000097:blood / Q000494:pharmacology*; D001549:Benzamides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000633:toxicity; D020117:Cisapride; D002945:Cisplatin / Q000633:toxicity; D019327:Copper Sulfate / Q000633:toxicity; D004285:Dogs; D004298:Dopamine / Q000378:metabolism / Q000633:toxicity; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009116:Muscarine / Q000378:metabolism / Q000633:toxicity; D009538:Nicotine / Q000378:metabolism / Q000633:toxicity; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D011869:Radioligand Assay; D012844:Sincalide / Q000378:metabolism / Q000633:toxicity; D013329:Structure-Activity Relationship; D014839:Vomiting / Q000188:drug therapy
D000897:Anti-Ulcer Agents; D001549:Benzamides; D010880:Piperidines; C058308:ecabapide; D009538:Nicotine; D009116:Muscarine; D015740:Calcitonin Gene-Related Peptide; D019327:Copper Sulfate; D012844:Sincalide; D002945:Cisplatin; D020117:Cisapride; D004298:Dopamine