Description:

Kb: 0.17 nM

Neurokinin NK1 receptors have been shown to play a role in a variety of behavioral responses in both animals and humans that has lead to the development of selective antagonists for this receptor. Principal of NK1 antagonists is their inhibitory effects against emesis induced by a variety of emetogenic stimuli. Rolapitant (SCH 619734) is a potent, selective and orally active neurokinin NK1 receptor antagonist.

In vitro: In vitro studies indicate that rolapitant HCl has a high affinity for the human NK1 receptor of 0.66 nM and high selectivity over the human NK2 and NK3 of >1000-fold, as well as preferential affinity for human, guinea pig, gerbil and monkey NK1 receptors over mouse, rat and rabbit. Rolapitant HCl is a functionally competitive antagonist with a calculated Kb of 0.17 nM. [1].

In vivo: Rolapitant HCl reversed NK1 agonist-induced foot tapping in gerbils following both intravenous and oral administration up to 24 hours at a minimal effective dose of 0.1 mg/kg. Rolapitant HCl was efficacious at 0.1 and 1 mg/kg in both acute and delayed emesis models in ferrets, respectively, which is consistent with clinical data for other NK1 antagonists [1].

Clinical trial: Rolapitant HCl is superior to placebo in reducing emetic episodes after surgery and reduces the incidence of vomiting in a dose-dependent manner. No differences were observed in side effect profile between rolapitant and placebo [2].

Reference:
[1] Duffy RA, Morgan C, Naylor R, Higgins GA, Varty GB, Lachowicz JE, Parker EM.? Rolapitant (SCH 619734): a potent, selective and orally active neurokinin NK1 receptor antagonist with centrally-mediated antiemetic effects in ferrets. Pharmacol Biochem Behav. 2012 Jul;102(1):95-100.
[2] Gan TJ, Gu J, Singla N, Chung F, Pearman MH, Bergese SD, Habib AS, Candiotti KA, Mo Y, Huyck S, Creed MR, Cantillon M; Rolapitant Investigation Group.? Rolapitant for the prevention of postoperative nausea and vomiting: a prospective, double-blinded, placebo-controlled randomized trial. Anesth Analg. 2011 Apr;112(4):804-12.