Effect of Y-25130, a selective 5-hydroxytryptamine3 receptor antagonist, on gastric emptying in mice.
The effect of Y-25130 on gastric emptying of nutrient test meals (solid chow) was examined in mice. In a dose range of 0.01-1 mg/kg, p.o., Y-25130 significantly accelerated gastric emptying of solid meals in a dose-dependent manner, at an ED30 of 0.021 mg/kg. Other 5-hydroxytryptamine3 receptor antagonists and prokinetic agents having 5-hydroxytryptamine3 receptor antagonistic properties accelerated the emptying of solid meals in the following rank order of potency: Y-25130 = granisetron > or = tropisetron > ondansetron > cisapride > metoclopramide. The acceleration of the gastric emptying showed a good correlation with the antagonistic potencies of these compounds on 5-hydroxytryptamine3 receptors, determined by the inhibition test of the von Bezold-Jarisch reflex in anesthetized rats (r2 = 0.99). Domperidone (1 and 10 mg/kg, p.o.) and trimebutine (10 and 100 mg/kg, p.o.) failed to increase the rate of emptying from the stomach. Cisplatin (30 mg/kg, i.p.), a chemotherapeutic agent, significantly delayed the gastric emptying of solid meals, and Y-25130 (0.1-1 mg/kg, p.o.) prevented such a delay in emptying in a dose-dependent manner. These results suggest that Y-25130 accelerates the gastric emptying in mice by antagonism of the 5-hydroxytryptamine3 receptor.
Haga
K
K
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Asano
K
K
Inaba
K
K
Morimoto
Y
Y
Setoguchi
M
M
D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020117:Cisapride; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects*; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D017294:Ondansetron / Q000008:administration & dosage / Q000494:pharmacology; D010078:Oxazines / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D014287:Trimebutine / Q000008:administration & dosage / Q000494:pharmacology; D000077526:Tropisetron
D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D020117:Cisapride; D004294:Domperidone; D017829:Granisetron; D007211:Indoles; D008787:Metoclopramide; D017294:Ondansetron; D010078:Oxazines; D010880:Piperidines; D012702:Serotonin Antagonists; D014287:Trimebutine; D000077526:Tropisetron; C070671:azasetron