Antiemetic Effects of YM060, a Potent and Selective Serotonin (5HT)3-Receptor Antagonist, in Ferrets and Dogs.

• Kamato Takeshi

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Miyata Keiji

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Ito Hiroyuki

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Yuki Hidenobu

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Yamano Mayumi

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

• Honda Kazuo

  Medicinal Research Laboratories 1, Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd.

抄録

YM060, (R)-5-[(1-methyl-3-indolyl)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole hydrochloride, is a new serotonin (5HT)₃-receptor antagonist. We examined the effects of YM060 on chemotherapeutic agent-, apomorphine- and copper sulfate-induced emesis. Intravenous YM060 potently prevented cisplatin (10 mg/kg, i.v.)-induced emesis with ED₅₀ values of 0.06 (0.05-0.07) μg/kg, i.v. in ferrets. Based on the ED₅₀ values, YM060 was 300, 20 and 100 times more potent than ondansetron, granisetron and the S-isomer of YM060, respectively. The relative potencies of these drugs described above were similar to those in the previously reported 5HT₃-receptor antagonism. YM060 given orally also potently inhibited cisplatin (10 mg/kg, i.p.)- and cyclophosphamide (200 mg/kg, i.p.)-induced emesis in ferrets with ED₅₀ values of 0.1 (0.09-0.11) and 0.02 (0.16-0.27) μg/kg, p.o., respectively. All tested 5HT₃-receptor antagonists including YM060 failed to prevent apomorphine (0.1 mg/kg, s.c.)-induced emesis in dogs and copper sulfate (1%, 10ml, p.o.)-induced emesis in ferrets. Our data indicate that YM060 is a highly potent inhibitor of chemotherapeutic agent-induced emesis and that the antiemetic effect of YM060 may be depend on 5HT₃-receptor antagonism.

収録刊行物

• Jpn.J.Pharmacol.

  Jpn.J.Pharmacol. 57 (3), 387-395, 1991

  公益社団法人 日本薬理学会

キーワード

• Pharmacology

詳細情報

• CRID: 1390282679264163072
• NII論文ID: 130000833242
• NII書誌ID: AA00691188
• DOI: 10.1254/jjp.57.387
• COI: 1:CAS:528:DyaK38XltFeruw%3D%3D
• ISSN: 13473506
• ISSN: 00215198
• PubMed: 1813664
• Web Site: https://search.jamas.or.jp/link/ui/1993146369
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
• 抄録ライセンスフラグ: 使用不可