Masakazu Saeki1,*, Michinori Sakai1, Ryo Saito2, Hisahiko Kubota2, Hideto Ariumi2, Yukio Takano2, Atsushi Yamatodani3 and Hiro-o Kamiya2
1Fundamental Research Laboratories, Hisamitsu Pharmaceutical Co., Inc., Tsukuba 305-0856, Japan
2Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka 814-0180, Japan
3Department of Medical Physics, School of Allied Health Sciences, Faculty of Medicine, Osaka University, Osaka 565-0871, Japan
*Corresponding author. Present address for correspondence: Formulation Research Laboratories, Hisamitsu Pharmaceutical Co., Inc., 408 Tashirodaikan-machi, Tosu, Saga 841-0017, Japan
FAX: +81-942-85-0593, E-mail: Masakazu_Saeki@hisamitsu.co.jp
Abstract: The effects of a novel tachykinin NK1-receptor antagonist HSP-117 {(2S,3S)-3-[(5-isopropyl-2,3-dihydrobenzofuran-7-yl)methyl]amino-2-phenylpiperidine dihydrochloride} on cisplatin-induced pica, i.e., the eating of nonnutritive substances such as kaolin were examined in rats. HSP-117 inhibited kaolin intake in a dose-dependent manner for 2 days. The 5-HT3-receptor antagonist ondansetron inhibited only on the first day, but not on the second day. These results indicate that the cisplatin-induced kaolin intake on the first day is related to both 5-HT3- and NK1 receptors, while only the NK1 receptor is involved on the second day. Thus, cisplatin-induced continuous pica in rats represents a useful model of not only acute but also delayed emesis.
Keywords: Cisplatin-induced pica, Tachykinin NK1-receptor antagonist, Delayed emesis
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