EFFECT OF ZATOSETRON ON IPECAC-INDUCED EMESIS IN DOGS AND HEALTHY-MEN

Serotonin receptor (5-HT3) antagonists provide effective antiemetic th erapy in cancer patients receiving emetogenic chemotherapy, such as ci splatin. Animal studies have shown that 5-HT3 receptor antagonists als o have antiemetic activity in ipecac-induced emesis. The authors inves tigated the antiemetic activity of zatosetron maleate, a 5-HT3 recepto r antagonist, on ipecac-induced emesis in dogs and healthy men. They a lso evaluated the effect of ipecac administration on serotonin release and metabolism by measuring urinary 5-hydroxyindoleacetic acid (5-HIA A) excretion in healthy men. In separate randomized, placebo-controlle d trials, 20 dogs received zatosetron intravenously and eight healthy men received zatosetron (50 mg) orally, followed by ipecac syrup. In b oth trials, emetic response to ipecac was recorded, including the numb er and time of vomits and retches. Zatosetron treatment inhibited and delayed ipecac-induced emesis in both groups. In dogs, zatosetron inhi bited ipecac-induced emesis in a dose-dependent manner with a 100-mu g /kg dose producing complete inhibition. In men, zatosetron administrat ion resulted in fewer emetic episodes after ipecac than had occurred w ith placebo administration (P = .03); vomiting was completely inhibite d by zatosetron. In men, ipecac administration did not affect the urin ary 5-HIAA/creatinine ratio (mg/g) or 5-HIAA excretion rate (mu g/hour ). Our study demonstrates that zatosetron has similar efficacy on ipec ac-induced emesis in healthy men, as has been shown previously with ot her 5-HT3 receptor antagonists in chemotherapy-induced emesis in cance r patients. We did not observe the increase of urinary 5-HIAA in our s tudy with ipecac-induced emesis, however, as has been described previo usly in cisplatin-induced emesis. Our study indicates that ipecac-indu ced emesis may be a useful model for testing 5-HT3 receptor antagonist s for antiemetic activity in dogs and healthy men.