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.
de la Puente-Redondo
V
V
Veterinary Medicine Research & Development, Pfizer Ltd., Sandwich, Kent, UK.
Tingley
F D
FD
Schneider
R P
RP
Hickman
M A
MA
D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D004285:Dogs; D005849:Gerbillinae / Q000378:metabolism*; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects*; D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000494:pharmacology
D000932:Antiemetics; D064729:Neurokinin-1 Receptor Antagonists; D011812:Quinuclidines; C518176:maropitant