Resiniferatoxin antagonizes cisplatin-induced emesis in dogs and ferrets

• Published in: European journal of pharmacology Vol. 442; no. 3; pp. 273 - 278
• Main Authors: Yamakuni, Hisashi, Sawai-Nakayama, Hiroe, Imazumi, Katsunori, Maeda, Yasue, Matsuo, Masahiko, Manda, Toshitaka, Mutoh, Seitaro
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.05.2002; Elsevier
• Subjects: acute; Acute Disease; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - toxicity; Antiparkinson Agents - administration & dosage; Antiparkinson Agents - toxicity; Apomorphine; Apomorphine - administration & dosage; Apomorphine - toxicity; Biological and medical sciences; Cisplatin - administration & dosage; Cisplatin - toxicity; delayed; Diterpenes - pharmacology; Dog; Dogs; Drug toxicity and drugs side effects treatment; Emesis; Female; Ferret; Ferrets; Male; Medical sciences; Pharmacology. Drug treatments; Time Factors; Toxicity: digestive system; Vanilloid; Vomiting - chemically induced; Vomiting - prevention & control; Vanilloid; Dog; Ferret; Emesis; Apomorphine; Antineoplastic agent; Fissipedia; Carnivora; Drug combination; Capsaicin; Toxicity; Biological activity; Cisplatin; Prevention; Toxin; Vertebrata; Mammalia; Vomiting; Analog; Animal; Digestive diseases; Subcutaneous administration; Vanilloid receptor; Antiemetic; Platinum II Complexes
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(02)01541-8

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 μg/kg, s.c.) 30 min before the injection of cisplatin markedly prevented acute emesis induced by cisplatin. When animals were given resiniferatoxin (10 μg/kg, s.c.) 24 h prior to cisplatin, the emesis was still inhibited, but not significantly. Resiniferatoxin (10 μg/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 μg/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 μg/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 μg/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.