Serotonin receptor (5-HT3) antagonists provide effective
antiemetic therapy in
cancer patients receiving emetogenic
chemotherapy, such as
cisplatin. Animal studies have shown that
5-HT3 receptor antagonists also have
antiemetic activity in
ipecac-induced
emesis. The authors investigated the
antiemetic activity of
zatosetron maleate, a
5-HT3 receptor antagonist, on
ipecac-induced
emesis in dogs and healthy men. They also evaluated the effect of
ipecac administration on
serotonin release and metabolism by measuring urinary 5-hydroxyindoleacetic
acid (5-HIAA) excretion in healthy men. In separate randomized, placebo-controlled trials, 20 dogs received
zatosetron intravenously and eight healthy men received
zatosetron (50 mg) orally, followed by
ipecac syrup. In both trials,
emetic response to
ipecac was recorded, including the number and time of vomits and retches.
Zatosetron treatment inhibited and delayed
ipecac-induced
emesis in both groups. In dogs,
zatosetron inhibited
ipecac-induced
emesis in a dose-dependent manner with a 100-micrograms/kg dose producing complete inhibition. In men,
zatosetron administration resulted in fewer
emetic episodes after
ipecac than had occurred with placebo administration (P = .03);
vomiting was completely inhibited by
zatosetron. In men,
ipecac administration did not affect the urinary 5-HIAA/
creatinine ratio (mg/g) or
5-HIAA excretion rate (microgram/hour). Our study demonstrates that
zatosetron has similar efficacy on
ipecac-induced
emesis in healthy men, as has been shown previously with other
5-HT3 receptor antagonists in
chemotherapy-induced
emesis in
cancer patients. We did not observe the increase of urinary
5-HIAA in our study with
ipecac-induced
emesis, however, as has been described previously in
cisplatin-induced
emesis.(ABSTRACT TRUNCATED AT 250 WORDS)