Improvement of cisplatin-induced emesis and delayed gastric emptying by KB-R6933, a novel 5-HT3 receptor antagonist

The effects of a novel 5-hydroxytryptamine(3) (5-HT3) receptor antagonist, KB-R6933, 6-amino5-chloro-1-isopropyl-2-(4-methyl-1-piperazinyl)-benzimidaz ole dimaleate, on emesis and delayed gastric emptying induced by cisplatin were assessed in experimental models. Prophylactic intravenous or oral trea tment with KB-R6933 prolonged the latent period until the first emetic epis ode and decreased the number of emetic episodes induced by cisplatin in fer rets. KB-R6933 immediately inhibited the subsequent emesis when administere d 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. (C) 1999 Elsevier Science Inc. All rights reserved.