In vitro and in vivo pharmacological characterization of the novel NK1 receptor selective antagonist Netupitant

► Netupitant behaves in vitro as a highly potent and selective NK1 receptor antagonist. ► In bioassay washout experiments, Netupitant displayed persistent (up to 5 h) antagonist effects. ► Netupitant antagonizes nociceptive responses to intrathecal substance P in mice. ► Netupitant prevents foot tapping induced by a NK1 agonist in gerbils showing long lasting effects. ► Netupitant is as a brain penetrant, orally active, potent and selective NK1 antagonist.