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Effect of Zatosetron on Ipecac‐Induced Emesis in Dogs and Healthy Men
Author(s) -
Schwartz Steven M.,
Goldberg Mark J.,
Gidda Jaswant S.,
Cerimele Benito J.
Publication year - 1994
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1994.tb03994.x
Subject(s) - antiemetic , medicine , vomiting , placebo , pharmacology , excretion , antagonist , receptor antagonist , anesthesia , oral administration , ondansetron , receptor , alternative medicine , pathology
Serotonin receptor (5‐HT 3 ) antagonists provide effective antiemetic therapy in cancer patients receiving emetogenic chemotherapy, such as cisplatin. Animal studies have shown that 5‐HT 3 receptor antagonists also have antiemetic activity in ipecac‐induced emesis. The authors investigated the antiemetic activity of zatosetron maleate, a 5‐HT 3 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‐μg/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 (μg/hour). Our study demonstrates that zatosetron has similar efficacy on ipecac‐induced emesis in healthy men, as has been shown previously with other 5‐HT 3 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. Our study indicates that ipecac‐induced emesis may be a useful model for testing 5‐HT 3 receptor antagonists for antiemetic activity in dogs and healthy men .