Potency, efficacy, and selectivity of GR64349 at human recombinant neurokinin NK2 and NK1 receptors

•The affinity and potency of GR64349 for NK2 and NK1 receptors was examined.•Binding affinity was ˜1200-fold higher for NK2 than NK1 receptors.•Potency was 500-1,400-fold higher at NK2 than NK1 receptors in functional assays.•GR64349 is the most selective NK2 receptor agonist described to date. The affinity, potency, efficacy, and selectivity of the NK2 receptor agonist GR64349 ([Lys3,Gly8,-R-γ-lactam-Leu9]NKA(3–10)) at human recombinant NK2 and NK1 receptors was examined. In radioligand binding studies, GR64349 displaced [125I]-NKA binding to NK2 receptors with high affinity (pKi 7.77 + 0.10) but only weakly displaced [3H]-septide binding to NK1 receptors (pKi