TABLE 1

Binding affinities of flunitrazepam and zolpidem for α1β2γ2s WT and α1β2ϰ receptors

Values shown are the mean ± S.E.M. for n number of independent experiments. KI is the equilibrium dissociation constant (apparent affinity) of the unlabeled ligand. KI values for flunitrazepam were determined by [3H]flunitrazepam saturation and competition binding experiments. KI values for zolpidem were determined by the displacement of [3H]flunitrazepam. Statistical differences between WT and chimera logKI values were determined using one-way analysis of variance with Dunnett's post test.


GABAR

Flunitrazepam

Zolpidem
KI
n
KI
n
nM nM
α1β2γ2s 8.4 ± 1.2 35 56.3 ± 3.8 7
α1β2ϰ161 10.9 ± 2.0 4 478 ± 13** 4
α1β2ϰ167 12.8 ± 2.3 7 486 ± 18** 3
α1β2ϰ185 14.1 ± 22 3 518 ± 73** 3
α1β2ϰ192 3.7 ± 0.6 3 16.5 ± 1.5** 3
α1β2ϰ198
7.8 ± 10
4
54.3 ± 18
4
  • ** Significantly different from α1β2γ2 WT (P < 0.01).