THE TACHYKININ NK(1) RECEPTOR ANTAGONIST CP-99,994 ATTENUATES CISPLATIN-INDUCED EMESIS IN THE FERRET

The tachykinin NK1 receptor antagonist CP-99,994 S,3S)-3-(2-methoxyben zylamino)-2-phenylpiperidine) (0.3-3 mg/kg i.v.), but not its inactive enantiomer CP-100,263, attenuated the retching and vomiting induced b y cisplatin (10 mg/kg i.v.) in the ferret. CP-99,994, 3 mg/kg i.v., pr evented vomiting in all ferrets tested, Since substance P is the prefe rred ligand at the NK1 receptor subtype these data support a role for the release of this peptide during the emetic response induced by cyto toxic chemotherapeutic agents.