rac-Aprepitant-d4 is intended for use as an internal standard for the quantification of aprepitant by GC- or LC-MS. Aprepitant an antiemetic compound and antagonist of the neurokinin-1 (NK1) receptor (Ki = 3 nM; IC50 = 0.09 nM for the human receptor).1,2 It is selective for NK1 over NK3 receptors (Ki = 454.1 nM for human NK3).1 In vivo, aprepitant (1 mg/kg) prevents plasma extravasation into the esophagus of guinea pigs induced by substance P .3 It also reduces NK1-agonist-induced foot tapping in gerbils. Formulations containing aprepitant have been used to prevent chemotherapy-induced nausea and vomiting.
1.Bissantz, C., Bohnert, C., Hoffmann, T., et al.Identification of a crucial amino acid in the helix position 6.51 of human tachykinin neurokinin 1 and 3 receptors contributing to the insurmountable mode of antagonism by dual NK1/NK3 antagonistsJ. Med. Chem.55(11)5061-5076(2012) 2.Finke, P.E., Meurer, L.C., Levorse, D.A., et al.Cyclopentane-based human NK1 antagonists. Part 1: Discovery and initial SARBioorg. Med. Chem. Lett.16(17)4497-4503(2006) 3.Meurer, L.C., Finke, P.E., Owens, K.A., et al.Cyclopentane-based human NK1 antagonists. Part 2: Development of potent, orally active, water-soluble derivativesBioorg. Med. Chem. Lett.16(17)4504-4511(2006)