THE ACTION OF THE NK1 TACHYKININ RECEPTOR ANTAGONIST, CP-99,994, IN ANTAGONIZING THE ACUTE AND DELAYED EMESIS INDUCED BY CISPLATIN IN THE FERRET

1 The anti-emetic effects of the NK1 tachykinin receptor antagonist, C P 99,994 (10 mg kg(-1)) were investigated in the ferret using a cispla tin-induced acute (day 1) and delayed (day 2 and 3) retching and vomit ing model. 2 With a single cisplatin (10 mg kg(-1)) emetogenic challen ge, the i.p. administration of CP 99,994 given as a single injection i mmediately following the first emetic episode, promptly abolished the retching and vomiting for a 4 h period. CP 99,994 was as efficacious a s ondansetron (1.0 mg kg(-1)). The general toxicity of cisplatin 10 mg kg(-1) precluded its use in studies of delayed emesis. 3 With a singl e cisplatin (5 mg kg(-1)) emetogenic challenge, the single administrat ion of either CP 99,994 (10 mg kg(-1)) or ondansetron (1.0 mg kg(-1)) immediately following the first emetic episode markedly reduced or abo lished the retching and vomiting for 4 h. Such single treatments faile d to modify significantly the intensity of delayed emesis appearing on the second and third day.4 With a cisplatin (5 mg kg(-1)) emetogenic challenge, administration of CP 99,994 (10 mg kg(-1)) at 8 hourly inte rvals, the first injection being administered 30 s post cisplatin, was associated with 4 or more abolitions of emesis during both the acute and delayed phase. A 4 hourly administration of CP 99,994 for 20 h dur ing delayed emesis completely abolished the retching and vomiting.5 It is concluded that cisplatin 5 mg kg(-1) provides an emetogenic challe nge causing an acute and delayed phase of retching and vomiting and th at CP 99,994 can abolish both phases. The results may be relevant to t he understanding and treatment of chemotherapy-induced emesis in man.