title: Inhibitory effect of zacopride on Cisplatin-induced delayed emesis in ferrets.
abstract: We evaluated the antiemetic effect of zacopride, a potent 5-HT3-receptor antagonist with 5-HT4-receptor agonist properties, on delayed emesis caused by cisplatin (5 mg/kg, i.p.) in ferrets, compared with granisetron, a selective 5-HT3-receptor antagonist. Multiple intravenous injections of zacopride at 1 mg/kg, a dose that completely inhibited acute emesis caused bycisplatin (10 mg/kg, i.v.), significantly reduced delayed emesis. Granisetron (3.2 mg/kg) also reduced delayed emesis but this failed to reach statistical significance. The present study suggests that a combined 5-HT3-receptor antagonist/5-HT4-receptor agonist, like zacopride, may be useful against both acute and delayed emesis induced by cancer chemotherapy.
authors.affiliation: Department of Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Yodogawa, Osaka, Japan. hisashi.yamakuni@jp.astellas.com
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamakuni
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakayama
authors.forename: Shigeo
authors.initials: S
authors.lastname: Matsui
authors.forename: Katsunori
authors.initials: K
authors.lastname: Imazumi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Matsuo
authors.forename: Seitaro
authors.initials: S
authors.lastname: Mutoh
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001549:Benzamides / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005289:Ferrets; D017829:Granisetron / Q000494:pharmacology; D008297:Male; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D001549:Benzamides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002945:Cisplatin; D017829:Granisetron; D012702:Serotonin Antagonists; C055971:zacopride