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.