Table 1

Binding affinities of BZD site ligands for wild-type, chimeric, and mutant chimeric GABAA receptors

ReceptorFlunitrazepamRo15-4513Ro15-1788
KInKI-mut/KI-αβγKInKI-mut/KI-αβγKInKI-mut/KI-αβγ
nM nM nM
αβγ9.9  ± 0.8171.05.2  ± 1.4101.04.5  ± 0.5111.0
αβχ8217.5  ± 4.391.839.0  ± 4.387.515.3  ± 3.563.4
 αβχ65-S81T25.6  ± 1.322.648.3  ± 8.579.323.8  ± 7.165.3
 αβχ65-R79A17.0  ± 1.421.768.0  ± 3.5313.165.1  ± 9.11-d 514.5
 αβχ65-V76I32.5  ± 7.623.3148.5  ± 23.51-d 328.654.3  ± 9.91-d 512.1
 αβχ65-NAIN1-e 25.9  ± 3.942.6140.5  ± 17.01-d 427.065.7  ± 6.41-d 414.6
αβχ6523.7  ± 3.662.4129.6  ± 5.61-d 324.943.3  ± 4.51-c 39.6
 αβχ56-F58Y/T60N/F62I82.2  ± 9.01-b 38.3N.D.N.D.
 αβχ56-T60N/F62I219.3  ± 18.81-b 322.2N.D.N.D.
 αβχ56-I57M/F58Y/T60N45.7  ± 13.21-a 34.6N.D.N.D.
 αβχ56-I57M/F58Y55.8  ± 9.11-b 35.6N.D.N.D.
 αβχ56-I57M231.7  ± 31.3223.4N.D.N.D.
αβχ56>100,000N.D.N.D.
αβχ40>100,000N.D.N.D.

KI values were determined by displacement of [3H]flunitrazepam binding. Results shown are the mean ± S.E.; n is the number of independent experiments. Statistical differences between log KI values were determined by one-way ANOVA using Dunnett's post test. The flunitrazepam affinity for αβχ56-I57M was not included in the statistical analysis due to n = 2, however, the trend suggests that it is significantly different from αβχ65.

  • 1-a Significantly different from αβχ65 (P < .05).

  • 1-b Significantly different from αβχ65 (P< .01).

  • 1-c Significantly different from αβχ82 (P< .05).

  • 1-d Significantly different from αβχ82 (P< .01).

  • 1-e αβχ56-S67N/D68A/H69I/D70N.

  • N.D., data not determined.