Antiemetic effect of a tachykinin NK 1 receptor antagonist GR205171 on cisplatin-induced early and delayed emesis in the pigeon

• Published in: European journal of pharmacology Vol. 461; no. 2; pp. 197 - 206
• Main Authors: Tanihata, Sachiko, Oda, Satoko, Kakuta, Sachiko, Uchiyama, Toshimitsu
• Format: Journal Article
• Language: English; Japanese
• Published: Elsevier B.V 2003
• Subjects: Cisplatin; Emesis; GR205171; Pigeon; Tachykinin NK 1 receptor antagonist; Tachykinin NK 1 receptor antagonist; Pigeon; Emesis; Cisplatin; GR205171
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(03)01311-6

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 ([(2 S- cis)- N-((2-methoxy-5(5-(trifluoromethyl)-1 H-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 μg/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 μg/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.