1. The
anti-emetic effects of the NK1
tachykinin receptor antagonist,
CP 99,994 (10 mg kg-1) were investigated in the ferret using a
cisplatin-induced acute (day 1) and delayed (day 2 and 3) retching and
vomiting model. 2. With a single
cisplatin (10 mg kg-1) emetogenic challenge, the i.p. administration of
CP 99,994 given as a single injection immediately following the first
emetic episode, promptly abolished the retching and
vomiting for a 4 h period.
CP 99,994 was as efficacious as
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 single
cisplatin (5 mg kg-1) emetogenic challenge, the single administration 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 abolished the retching and
vomiting for 4 h. Such single treatments failed 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 intervals, 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 during delayed
emesis completely abolished the retching and
vomiting. 5. It is concluded that
cisplatin 5 mg kg-1 provides an emetogenic challenge causing an acute and delayed phase of retching and
vomiting and that
CP 99,994 can abolish both phases. The results may be relevant to the understanding and treatment of
chemotherapy-induced
emesis in man.