Improvement of cisplatin-induced emesis and delayed gastric emptying by KB-R6933, a novel 5-HT3 receptor antagonist.
The effects of a novel 5-hydroxytryptamine3 (5-HT3) receptor antagonist, KB-R6933, 6-amino-5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)-benzimidazole dimaleate, on emesis and delayed gastric emptying induced by cisplatin were assessed in experimental models. Prophylactic intravenous or oral treatment with KB-R6933 prolonged the latent period until the first emetic episode and decreased the number of emetic episodes induced by cisplatin in ferrets. KB-R6933 immediately inhibited the subsequent emesis when administered to the ferrets which exhibited established vomiting after administration of cisplatin. In rats treated with cisplatin, the gastric emptying rate was significantly reduced. KB-R6933 reversed the reduction of gastric emptying induced by cisplatin. These results suggest that KB-R6933 is an antiemetic agent, and could improve the cisplatin-induced delay of gastric emptying.
Ozaki
A
A
Pharmaceuticals R&D Center, Kanebo, Ltd., Osaka, Japan. ozaki-a@po.iijnet.or.jp
Sukamoto
T
T
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001562:Benzimidazoles / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002945:Cisplatin / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D005746:Gastric Emptying / Q000187:drug effects*; D017829:Granisetron / Q000494:pharmacology; D008297:Male; D017294:Ondansetron / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002945:Cisplatin; D017829:Granisetron; D017294:Ondansetron; D010078:Oxazines; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; C121292:KB R6933; C070671:azasetron