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The neurokinin‐1 antagonist activity of maropitant, an antiemetic drug for dogs, in a gerbil model
Author(s) -
DE LA PUENTEREDONDO V.,
TINGLEY F. D.,
SCHNEIDER R. P.,
HICKMAN M. A.
Publication year - 2007
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2007.00847.x
Subject(s) - nk1 receptor antagonist , pharmacology , antiemetic , gerbil , antagonist , chemistry , agonist , anesthesia , substance p , medicine , receptor , neuropeptide , vomiting , biochemistry , ischemia
Maropitant is a novel synthetic nonpeptide neurokinin type 1 (NK 1 ) 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 NK 1 agonist GR73632. In comparison with CP‐122,721, a previously characterized NK 1 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 NK 1 receptor antagonist and help to support and explain its clinical potential as a broad‐spectrum antiemetic agent.