The neurokinin-1 antagonist activity of maropitant, an antiemetic drug for dogs, in a gerbil model.

Maropitant is a novel synthetic nonpeptide neurokinin type 1 (NK1) selective receptor antagonist, recently developed for use in the dog as an antiemetic. The in vivo functional activity of maropitant was investigated in the gerbil foot-tapping model, to determine the ability of maropitant to penetrate the central nervous system and inhibit foot-tapping induced by the selective NK1 agonist GR73632. In comparison with CP-122,721, a previously characterized NK1 receptor antagonist, maropitant (1 mg/kg by s.c. injection) was found to inhibit foot-tapping for significantly longer (P < 0.01). Inhibition of foot-tapping by maropitant was 100% at 2 h and approximately 50% at 8 h postdosing. The mean brain:plasma concentration ratio at 8 h post-treatment was 3.59. These data demonstrate the central functional action of maropitant as a selective and potent NK1 receptor antagonist and help to support and explain its clinical potential as a broad-spectrum antiemetic agent.