Antiemetic activity of the new 5-HT3 antagonist DAU 6215 in animal models of cancer chemotherapy and radiation.

Abstract	The antiemetic activity of DAU 6215, a novel antagonist of 5-HT3 receptors, was investigated in animal models of cytotoxic treatment-evoked emesis and compared with the antiemetic activity of ondansetron and metoclopramide. In dogs, vomiting was induced by i.v. cisplatin; in ferrets, the emetic response was elicited by i.v. doxorubicin or X-ray exposure. Pretreatment with 0.1-1 mg/kg DAU 6215 given i.v. or p.o. prevented the vomiting response to the different emetic agents. In the dog, the antiemetic potency of metoclopramide was 30 times lower than that of DAU 6215. Ondansetron was less potent than DAU 6215 against cisplatin and doxorubicin but was equally effective in the radiotherapy protocol. In this model, lengthening of the pretreatment time to 2 h did not affect the antiemetic efficacy of DAU 6215, whereas it decreased that of ondansetron. The results demonstrate that DAU 6215 is a highly effective and long-lasting inhibitor of cytotoxic treatment-induced emesis in different animal species.
Authors	A Sagrada, M Turconi, P Bonali, P Schiantarelli, R Micheletti, E Montagna, M Nicola, D R Algate, E M Rimoldi, A Donetti
Journal	Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 28 Issue 6 Pg. 470-4 ( 1991) ISSN: 0344-5704 [Print] Germany
PMID	1834359 (Publication Type: Comparative Study, Journal Article)
Chemical References	Antiemetics Benzimidazoles Bridged Bicyclo Compounds Bridged Bicyclo Compounds, Heterocyclic Imidazoles Serotonin Antagonists itasetron Ondansetron Doxorubicin Metoclopramide Cisplatin
Topics	Animals Antiemetics (therapeutic use) Benzimidazoles (therapeutic use) Bridged Bicyclo Compounds (therapeutic use) Bridged Bicyclo Compounds, Heterocyclic Cisplatin (adverse effects) Disease Models, Animal Dogs Dose-Response Relationship, Drug Doxorubicin (adverse effects) Drug Evaluation, Preclinical Female Ferrets Imidazoles (therapeutic use) Male Metoclopramide (therapeutic use) Neoplasms, Experimental (complications, drug therapy, radiotherapy) Ondansetron Serotonin Antagonists (therapeutic use) Time Factors Vomiting (etiology, prevention & control)

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