Resiniferatoxin antagonizes cisplatin-induced emesis in dogs and ferrets.
We evaluated the antiemetic activity of resiniferatoxin, an ultrapotent capsaicin analogue, on cisplatin- and apomorphine-induced emesis in dogs, and on cisplatin-induced acute and delayed emesis in ferrets. In the dog, resiniferatoxin (10 microg/kg, s.c.) 30 min before the injection of cisplatin markedly prevented acute emesis induced by cisplatin. When animals were given resiniferatoxin (10 microg/kg, s.c.) 24 h prior to cisplatin, the emesis was still inhibited, but not significantly. Resiniferatoxin (10 microg/kg, s.c.) 30 min before the administration of apomorphine also significantly reduced the emetic responses induced by apomorphine in dogs. In the ferret, resiniferatoxin (10 microg/kg, s.c.) 30 min prior to cisplatin completely inhibited acute emesis caused by cisplatin (10 mg/kg, i.p.). When ferrets were given resiniferatoxin (10 microg/kg, s.c.) 16 h prior to cisplatin, the emesis was still significantly inhibited. Cisplatin (5 mg/kg, i.p.) induced both acute (0-24 h) and delayed (24-72 h) phase emesis, and a single injection of resiniferatoxin (10 microg/kg, s.c.) at 36 h after cisplatin significantly reduced subsequent emetic responses during the 36-72 h period. These results suggest that resiniferatoxin-related vanilloids may be useful drugs against both acute and delayed emesis induced by cancer chemotherapy.
Yamakuni
Hisashi
H
Department of Cancer and Urology, Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Kashima 2-1-6, Yodogawa, Osaka 532-8514, Japan. hisashi_yamakuni@po.fujisawa.co.jp
Sawai-Nakayama
Hiroe
H
Imazumi
Katsunori
K
Maeda
Yasue
Y
Matsuo
Masahiko
M
Manda
Toshitaka
T
Mutoh
Seitaro
S
D000208:Acute Disease; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000633:toxicity; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000633:toxicity; D001058:Apomorphine / Q000008:administration & dosage / Q000633:toxicity; D002945:Cisplatin / Q000008:administration & dosage* / Q000633:toxicity; D004224:Diterpenes / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005289:Ferrets; D008297:Male; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000970:Antineoplastic Agents; D000978:Antiparkinson Agents; D004224:Diterpenes; C024353:resiniferatoxin; D001058:Apomorphine; D002945:Cisplatin