The antiemetic profile of Y-25130, a new selective 5-HT3 receptor antagonist.
Y-25130( (+/-)N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4-dihydro - 2H-1,4-benzoxazine-8-carboxamide hydrochloride) is a potent and selective 5-HT3 receptor antagonist free of dopamine receptor blocking activity. This compound was effective against emesis induced in animals by cytotoxic drugs or by total body X-radiation. When given prophylactically, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. Y-25130, at the dose of 0.3 mg/kg i.v., almost completely inhibited X-radiation-induced emesis in ferrets. When given during emesis, the doses required to completely inhibit cisplatin-induced emesis in dogs and doxorubicin- and cyclophosphamide-induced emesis in ferrets were 0.1 and 0.3 mg/kg i.v., respectively. The i.v. dose of 0.3 mg/kg of Y-25130 was enough to almost completely inhibit cisplatin-induced emesis in dogs for 24 h. From these results, it is suggested that Y-25130 may become an effective antiemetic drug against emesis induced by anticancer therapy.
Fukuda
T
T
Research Laboratories, Yoshitomi Pharmaceutical Industries Ltd., Fukuoka, Japan.
Setoguchi
M
M
Inaba
K
K
Shoji
H
H
Tahara
T
T
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002945:Cisplatin / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage; D004285:Dogs; D004317:Doxorubicin / Q000008:administration & dosage; D005289:Ferrets; D007700:Kinetics; D010078:Oxazines / Q000494:pharmacology*; D011869:Radioligand Assay; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists; D013997:Time Factors; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000932:Antiemetics; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010078:Oxazines; D017981:Receptors, Neurotransmitter; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; C070671:azasetron; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin