Antiemetic effect of a tachykinin NK1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon.
Cisplatin (4 mg/kg, i.v.) induced both early emesis, which appears within the first 8-h period, and delayed emesis, which appears between 8 and 48 h after its administration to pigeons. GR205171 ([(2S-cis)-N-((2-methoxy-5(5-(trifluoromethyl)-1H-tetrazol-1-yl)-phenyl) methyl)-2-phenyl-3-piperidinamine dihydrochloride]) administered intramuscularly (1-10 mg/kg) reduced significantly the number of emetic response to cisplatin: this reduction was 60-81% (P < 0.05) for early emesis and 48-64% (P < 0.05) for the delayed response. Intracerebroventricularly administered GR205171 (30 microg/kg) also reduced the number of emetic responses: 53% (P < 0.05) in early emesis and 88% (P < 0.05) in the delayed response. However, the latency time to the first emesis was not affected by GR205171. Direct injection of cisplatin (10 microg/kg) into the fourth ventricle produced emesis, which was reduced by GR205171 administered via the peripheral or central route. Substance P-immunoreactive fibres were distributed throughout the dorsal vagal complex. These results suggest that the antiemetic effect of GR205171 on both emetic responses to cisplatin acts on a central site, and that the onset of the emetic response may be mediated partly via GR205171-insensitive mechanisms.
Tanihata
Sachiko
S
Department of Pharmacology, Faculty of Medicine, Toho University, Omori-Nishi 5-21-16, Ota-ku, Tokyo 143-8540, Japan.
Oda
Satoko
S
Kakuta
Sachiko
S
Uchiyama
Toshimitsu
T
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage; D010856:Columbidae; D005260:Female; D007150:Immunohistochemistry; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000737:chemistry; D013373:Substance P / Q000032:analysis; D013777:Tetrazoles / Q000494:pharmacology*; D014630:Vagus Nerve / Q000737:chemistry; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D013777:Tetrazoles; D013373:Substance P; C103207:vofopitant; D002945:Cisplatin