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.