Neuroactive steroid inhibition of [35S]TBPS binding in human recombinant GABAA receptors
| Receptor | GABA | Compound13 | Compound 16 (Co 152791) | 3α,5α-P | |||
|---|---|---|---|---|---|---|---|
| IC50 | Imax | IC50 | Imax | IC50 | Imax | ||
| μM5-a | nM | % | nM | % | nM | % | |
| α1β2γ2L | 5 | 7.2 ± 1.0 | 77 ± 4 | 5.7 ± 1.4 | 81 ± 6 | 17.55-b | 103 |
| α2β2γ2L | 5 | 5.9 ± 0.7 | 80 ± 4 | 2.1 ± 0.2 | 85 ± 2 | 415-b | 105 |
| α3β2γ2L | 10 | 4.3 ± 0.5 | 81 ± 2 | 1.4 ± 0.3 | 93 ± 6 | 205-b | 109 |
| α4β3γ2L | 10 | 27 ± 10 | 24 ± 4 | 210 ± 70 | 40 ± 3 | 1700 ± 200 | 85 ± 4 |
| α5β2γ2L | 1 | 11.6 ± 0.4 | 76.9 ± 0.2 | 2.2 ± 0.6 | 85 ± 3 | 215-b | 112 |
| α6β3γ2L | 5 | 140 ± 60 | 16 ± 1 | 91 ± 24 | 39 ± 8 | 1060 ± 20 | 76 ± 7 |
IC50, Imax and Hill slope values for inhibition of 2 nM [35S]TBPS binding to human recombinant GABAA receptor combinations expressed in HEK 293 cells. Values are mean ± S.E. of at least three independent experiments. Hill slope values were not different from 1.0 (P < .05) except for Co 152791 in α1β2γ2L (1.7 ± 0.5) and α2β2γ2L (1.3 ± 0.1) membranes, and for compound 13 in α1β2γ2L (2.4 ± 0.7), α2β2γ2L (2.0 ± 0.2), α3β2γ2L (1.6 ± 0.1) and α5β2γ2L (constrained to 2.5) membranes.