Involvement of 5-HT3 receptors and vagal afferents in copper sulfate- and cisplatin-induced emesis in monkeys.
The emetic effects of copper sulfate and cisplatin and the potential involvement of vagal afferent fibers and 5-HT3 receptors in the emesis were investigated in cynomolgus monkeys. Retching and vomiting induced by both oral (100 mg/kg) and intravenous (20 mg/kg) copper sulfate were inhibited markedly by abdominal vagotomy. Furthermore, the emetic response induced by oral copper sulfate was strongly inhibited by intravenous ICS 205-930 (0.1 mg/kg), a 5-HT3 receptor antagonist. Cisplatin (3 mg/kg, i.v.) caused severe retching and vomiting, and the number of emetic responses was much greater than that in other species. The emetic response induced by cisplatin was inhibited markedly by abdominal vagotomy or concurrent administration of ICS 205-930 (3 x 0.1 mg/kg, i.v.). These results suggest that the monkey is more sensitive to cisplatin than other species and that the vagal afferent terminals and 5-HT3 receptors play an important role in the emetic response induced by copper sulfate and cisplatin.
Fukui
H
H
Drug Safety Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Yamamoto
M
M
Sasaki
S
S
Sato
S
S
D000284:Administration, Oral; D000818:Animals; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity*; D003300:Copper / Q000008:administration & dosage / Q000633:toxicity*; D019327:Copper Sulfate; D005260:Female; D007211:Indoles / Q000494:pharmacology; D007275:Injections, Intravenous; D008252:Macaca fascicularis; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D000077526:Tropisetron; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014839:Vomiting / Q000139:chemically induced*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D000077526:Tropisetron; D003300:Copper; D019327:Copper Sulfate; D002945:Cisplatin