Table 1. Pharmacological Evaluation of Fluorescent and Biotinylated Probesa.
human ρ1 GABAC receptor
% inhibition and IC50 μM (95% confidence interval) |
||||
---|---|---|---|---|
compound | spacer | 300 μM | 600 μMd | human α1β2γ2L GABAA receptor % inhibition at 300 μM |
(S)-4-ACPBPA (6) | 97 ± 3%b | inactiveg | ||
IC50 = 9.76, KB = 4.97 μMc | ||||
(R)-4-ACPBPA (7) | 92 ± 7%b | inactiveg | ||
KB = 59.3 μMc | ||||
(S)-4-ACPBPA-C1-NMA [(S)-11a] | 1 | 8 ± 2% | ||
(S)-4-ACPBPA-C3-NMA [(S)-11b] | 3 | 23 ± 4% | ||
(S)-4-ACPBPA-C4-NMA [(S)-11c] | 4 | 31 ± 2% | ||
(S)-4-ACPBPA-C5-NMA [(S)-11d] | 5 | 62 ± 7% | inactiveg | |
(R)-4-ACPBPA-C5-NMA [(R)-11d] | 5 | 56 ± 9% | inactiveg | |
(S)-4-ACPBPA-C6-NMA [(S)-11e] | 6 | 55 ± 3% | ||
(S)-4-ACPBPA-C7-NMA [(S)-11f] | 7 | 24 ± 8% | ||
(S)-4-ACPBPA-C10-NMA [(S)-11g] | 10 | 8 ± 3% | ||
(S)-4-ACPBPA-C5-NBD (12) | 5 | IC50 = 281.42 (274.96–332.11)e | inactiveg | |
IC50 = 193.27 (181.67–224.81)f | ||||
(S)-4-ACPBPA-C5-BODIPY (13) | 5 | IC50 = 103.14 (95.36–114.87)e | inactiveg | |
IC50 = 58.61 (45.37–71.63)f | ||||
(S)-4-ACPBPA-C0-biotin (15) | 0 | inactiveb | ||
(S)-4-ACPBPA-C5-biotin (16) | 5 | IC50 = 147.92 (139.45–174.13)e | 9 ± 7%g | |
IC50 = 76.54 (68.33–102.96)f |
Determined electrophysiologically in Xenopus laevis oocytes expressing the human ρ1 GABAC receptor or human α1β2γ2L GABAA receptors as previously described.9,10
Activity or percent inhibition by 300 μM compound of the current produced by a submaximal concentration of GABA (1 μM, EC50).
Data from ref (9).
Percent inhibition by 600 μM compound of the current produced by a submaximal concentration of GABA (1 μM, EC50), with a 5 min preincubation.
IC50 values for compounds without preincubation.
IC50 values for compounds with a 5 min preincubation.
Activity or percent inhibition by 300 μM compound of the current produced by a submaximal concentration of GABA (30 μM, EC50) without and with a 5 min preincubation. All data are means ± the standard error of the mean (n = 3 oocytes).