Effects of HSP-117, a novel tachykinin NK1-receptor antagonist, on cisplatin-induced pica as a new evaluation of delayed emesis in rats.
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.
Saeki
M
M
Fundamental Research Laboratories, Hisamitsu Pharmaceutical Co., Inc., Tsukuba, Japan. Masakazu_Saeki@hisamitsu.co.jp
Sakai
M
M
Saito
R
R
Kubota
H
H
Ariumi
H
H
Takano
Y
Y
Yamatodani
A
A
Kamiya
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001572:Benzofurans / Q000494:pharmacology*; D002945:Cisplatin / Q000009:adverse effects*; D006801:Humans; D064729:Neurokinin-1 Receptor Antagonists; D010842:Pica / Q000139:chemically induced*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D001572:Benzofurans; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C119466:HSP 117; D002945:Cisplatin