title: 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.affiliation: Instituto De Angeli (Boehringer Ingelheim Italia), Milano.
authors.forename: A
authors.initials: A
authors.lastname: Sagrada
authors.forename: M
authors.initials: M
authors.lastname: Turconi
authors.forename: P
authors.initials: P
authors.lastname: Bonali
authors.forename: P
authors.initials: P
authors.lastname: Schiantarelli
authors.forename: R
authors.initials: R
authors.lastname: Micheletti
authors.forename: E
authors.initials: E
authors.lastname: Montagna
authors.forename: M
authors.initials: M
authors.lastname: Nicola
authors.forename: D R
authors.initials: DR
authors.lastname: Algate
authors.forename: E M
authors.initials: EM
authors.lastname: Rimoldi
authors.forename: A
authors.initials: A
authors.lastname: Donetti
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002945:Cisplatin / Q000009:adverse effects; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005289:Ferrets; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008787:Metoclopramide / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000150:complications / Q000188:drug therapy* / Q000532:radiotherapy*; D017294:Ondansetron; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D013997:Time Factors; D014839:Vomiting / Q000209:etiology / Q000517:prevention & control
chemical_list: D000932:Antiemetics; D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; D012702:Serotonin Antagonists; C070191:itasetron; D017294:Ondansetron; D004317:Doxorubicin; D008787:Metoclopramide; D002945:Cisplatin