Antiemetic Effects of a Potent and Selective Neurokinin-1 Receptor Antagonist, FK886, on Cisplatin- and Apomorphine-Induced Emesis in Dogs
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- Yoshino Furukawa Takako
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Nakayama Hiroe
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Kikuchi Aya
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Imazumi Katsunori
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Yamakuni Hisashi
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Sogabe Hajime
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Yamasaki Sachiko
- Astellas Analytical Science Laboratories, Inc.
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- Takeshita Koji
- Astellas Analytical Science Laboratories, Inc.
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- Matsuo Masahiko
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Manda Toshitaka
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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- Uchida Wataru
- Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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抄録
The antiemetic properties of a novel neurokinin-1 (NK1) receptor antagonist, FK886 ([3,5-bis(trifluoromethyl)phenyl][(2R)-2-(3-hydroxy-4-methylbenzyl)-4-{2-[(2S)-2-(methoxymethyl)morpholin-4-yl]ethyl}piperazin-1-yl]methanone dihydrochloride), were studied in dog models of cisplatin- and apomorphine-induced emesis. Intravenously administered FK886 (0.32–1 mg/kg) significantly inhibited cisplatin-induced acute emesis during the 5-h observation period. Nearly complete inhibition was observed at 1 mg/kg. At an equivalent dose range, orally administered FK886 also significantly inhibited emesis, indicating good oral absorption. Similarly, FK886 inhibited apomorphine-induced emetic responses effectively following both intravenous and oral administration. The effects were long lasting, with 1.6 mg/kg of FK886 completely blocking apomorphine-induced retching and vomiting after a 12-h pretreatment period. Furthermore, FK886 showed rapid onset of antiemetic activity after oral administration. At doses of 0.32 mg/kg or more, a pretreatment time of 0.5 h was sufficient for complete inhibition of apomorphine-induced emetic responses. This fast onset after oral administration was supported by pharmacokinetic data, which demonstrated plasma levels of FK886 after oral administration reached levels similar to those 30 min after intravenous administration. These results suggest that FK886 has excellent antiemetic properties in dogs, and that its rapid-onset and long-lasting properties might make it a promising antiemetic agent.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (6), 974-979, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204631393792
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- NII論文ID
- 130003361444
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3snovFSjsA%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024524373
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- PubMed
- 23727919
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可