title: Pemirolast reduces cisplatin-induced kaolin intake in rats.
abstract: Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK(1) receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT(3) receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK(1) receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan. youko820@pharmst.med.kyushu-u.ac.jp
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tatsushima
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Naohiro
authors.initials: N
authors.lastname: Matsushita
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kurobe
authors.forename: Takehiro
authors.initials: T
authors.lastname: Kawashiri
authors.forename: Takahisa
authors.initials: T
authors.lastname: Yano
authors.forename: Ryozo
authors.initials: R
authors.lastname: Oishi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077608:Aprepitant; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D007616:Kaolin / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D017294:Ondansetron / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D011744:Pyrimidinones / Q000494:pharmacology*; D051381:Rats; D013373:Substance P / Q000134:cerebrospinal fluid
chemical_list: D000970:Antineoplastic Agents; D009025:Morpholines; D011725:Pyridines; D011744:Pyrimidinones; D000077608:Aprepitant; D007616:Kaolin; C055139:pemirolast; D013373:Substance P; D017294:Ondansetron; D003907:Dexamethasone; D002945:Cisplatin