TABLE 3

Summary of parameters from ligand cross-competition. All the values were obtained in 50 mM Tris-HCl, pH 7.4, at 22°C. Cross-competition were carried out in filter binding assays by varying concentrations of both competition partners with radioligand set at a constant level, and the data were fit to eq. 3 for homologous cross-competition or eq. 4 for heterologous cross-competition by nonlinear squares analysis to calculate Ki(1), the inhibition constant for partner one (I1), Ki(2), the inhibition constant for I2, and γ, the cooperativity factor for the interaction between I1 and I2.


Competition Pair

γ

Ki(1)

Ki(2)
I1
I2
nM nM
SPA with 125I-[MePhe7]NKB as the radioligand
    [MePhe7]NKB Talnetant >100 0.7 ± 0.1 4.4 ± 0.8
    [MePhe7]NKB Osanetant >100 0.5 ± 0.1 0.6 ± 0.1
    Talnetant Osanetant >100 3.1 ± 0.2 0.6 ± 0.1
Filter binding with [3H]SB222200 as the radioligand
    SB222200 Talnetant 70 1.26 ± 0.13 1.95 ± 0.19
    SB222200 Osanetant >100 1.10 ± 0.10 0.21 ± 0.02
    Talnetant
Osanetant
>100
2.00 ± 0.21
0.20 ± 0.02