The tachykinin NK1 receptor antagonist CP-99,994 attenuates cisplatin induced emesis in the ferret.
The tachykinin NK1 receptor antagonist CP-99,994 ((+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine) (0.3-3 mg/kg i.v.), but not its inactive enantiomer CP-100,263, attenuated the retching and vomiting induced by cisplatin (10 mg/kg i.v.) in the ferret. CP-99,994, 3 mg/kg i.v., prevented vomiting in all ferrets tested. Since substance P is the preferred ligand at the NK1 receptor subtype these data support a role for the release of this peptide during the emetic response induced by cytotoxic chemotherapeutic agents.
Tattersall
F D
FD
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Rycroft
W
W
Hargreaves
R J
RJ
Hill
R G
RG
D000704:Analysis of Variance; D000818:Animals; D002945:Cisplatin / Q000633:toxicity*; D005289:Ferrets; D007275:Injections, Intravenous; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy*
D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D015288:Neurokinin A; D002945:Cisplatin