Comparative evaluation of DQ-2511, a novel gastroprokinetic agent, with cisapride in ameliorative action on experimentally induced delayed gastric emptying.
We compared the main pharmacological effect of DQ-2511 (3-[[[2-(3,4-dimethoxyphenyl)- ethyl]carbamoyl]methyl]amino-N-methylbenzamide), a novel gastroprokinetic agent, with that of cisapride. Single oral administration of DQ-2511 (3-10 mg kg-1) caused similar significant improvements to delays in gastric emptying of semi-solid meals evoked by cholecystokinin-octapeptide (CCK8: 5 micrograms kg-1, i.v.) in monkeys, to that with cisapride (3 mg kg-1). A 2-week oral treatment of unilaterally vagotomized rats with DQ-2511 (1-10 mg kg-1) lessened delays in gastric emptying, whereas cisapride (0.3-10 mg kg-1) had no effect under the same experimental protocols. In anesthetized rats, bolus intravenous injection of either compound (60 micrograms kg-1) enhanced gastric motility determined by means of strain gauge force transducers. Electrophysiological investigations revealed that bolus injection of DQ-2511 (6-60 micrograms kg-1) depressed the afferent discharge rate of the ventral gastric branch of the vagus nerve, while cisapride showed no effect. These results suggest that the mechanism of ameliorative action of DQ-2511 on delayed gastric emptying may differ from that of cisapride.
Hatanaka
S
S
Exploratory Research Laboratories III, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan.
Kawarabayashi
K
K
Iseri
M
M
Tsubokura
K
K
Furuhama
K
K
Nijima
A
A
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D020117:Cisapride; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012453:Saimiri; D012844:Sincalide / Q000494:pharmacology*; D013270:Stomach / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D000897:Anti-Ulcer Agents; D001549:Benzamides; D010880:Piperidines; C058308:ecabapide; D012844:Sincalide; D020117:Cisapride