| 9085045 |
Minami M, Endo T, Tamakai H, Ogawa T, Hamaue N, Hirafuji M, Monma Y, Yoshioka M, Hagihara K: Antiemetic effects of N-3389, a newly synthesized 5-HT3 and 5-HT4 receptor antagonist, in ferrets. Eur J Pharmacol. 1997 Mar 5;321(3):333-42.
The antiemetic activity of N-3389 (endo-3,9-dimethyl-3,9-diazabicyclo [3,3,1] non-7-yl-1 H-indazole-3-carboxamide dihydrochloride), a new 5-HT3 and 5-HT4 receptor antagonist, against cisplatin-, cyclophosphamide- and copper sulfate-induced emesis was investigated using ferrets. We also examined the effects of these agents on abdominal afferent vagus nerve activity in anesthetized ferrets. Both intraperitoneal (0.1-1.0 mg/kg) and oral (0.1-1.0 mg/kg) administration of N-3389 produced dose-dependent antiemetic effects. The time-course of cisplatin (10 mg/kg, i.p.)-induced emesis in another group of ferrets paralleled the increase in abdominal afferent vagus nerve activity induced by cisplatin (10 mg/kg, i.p.) and was inhibited by pretreatment with N-3389 (1.0 mg/kg, i.v.). Furthermore, the cisplatin (10 mg/kg, i.p.)-induced increase in abdominal afferent vagus nerve activity was markedly reduced by an additional injection of N-3389 (0.1-1.0 mg/kg, i.v.) in a dose-dependent manner. The antiemetic effects exhibited by N-3389 are probably due to the inhibition of 5-HT3 and 5-HT4 receptors on the abdominal afferent vagus nerves. |
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