[Effect of the 5-HT3 receptor antagonist granisetron on estramustine phosphate sodium (Estracyt)-induced emesis in ferrets].
Estracyt(R) is an antimitotic drug used for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. In this study, we investigated the effect of a 5-HT3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (EMP), the active ingredient of Estracyt. To clarify the mechanism of action of EMP-induced emesis, we also investigated the effect of EMP on the release of serotonin (5-HT) in the isolated rat ileum. EMP (3 mg/kg, per os) induced 75.3+/-10.2 retching episodes and 7.5+/-1.3 vomiting episodes during a 2-h observation period. The latency to the first emetic response was 58.0+/-13.5 min. Granisetron (0.1 mg/kg, per os) administered 1 h before the administration of EMP reduced the number of EMP-induced retching and vomiting episodes to 1.3+/-1.3 and 1.0+/-1.0, respectively, and prolonged the latency by a factor of almost two. EMP (10-5 and 10-4 M) increased 5-HT release from isolated rat ileum, and 10 -7 M granisetron almost completely inhibited the increase induced by 10-4 M EMP. These results suggest that EMP induces nausea and vomiting via 5-HT release from the ileum, and that 5-HT3 receptor antagonists may be useful to prevent gastrointestinal adverse effects that occur during treatment with Estracyt.
Higashioka
Masaya
M
Research Laboratories, Nippon Shinyaku Co., Ltd., Japan.
Yamaguchi
Emi
E
Takatori
Shingo
S
Tanaka
Mitsushi
M
Kyoi
Takashi
T
D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects* / Q000494:pharmacology*; D004961:Estramustine / Q000009:adverse effects*; D005289:Ferrets; D017829:Granisetron / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D014839:Vomiting / Q000139:chemically induced* / Q000188:drug therapy*
D000932:Antiemetics; D018906:Antineoplastic Agents, Alkylating; D004961:Estramustine; D017829:Granisetron