The ability of nonsteroidal anti-inflammatory agents to modulate GABA responses at different receptor subtypes (etomidate and loreclezole are shown for comparison)
An equieffective concentration of GABA (EC50) was predetermined for each receptor subtype prior to modulation experiments. Results are the mean ± S.E.M. from 5 to 10 separate determinations and represent the total effect of the compound (modulatory and direct).
Maximal Potentiation (%) | EC50 (mM) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| β3 | β2 | β1 | β3 | β2 | β1 | |||||
| Etomidate | 158 ± 23 | 152 ± 20 | 107 ± 19 | 0.3 ± 0.1 | 0.5 ± 0.1 | 2.9 ± 0.8 | ||||
| Loreclezole | 62 ± 6 | 56 ± 3 | 15 ± 4 | 0.7 ± 0.1 | 1.8 ± 0.3 | >10 | ||||
| Mefenamic acid | 63 ± 5 | 80 ± 8 | 8 ± 13 | 2.1 ± 0.4 | 3.5 ± 0.8 | ND | ||||
| Flufenamic acid | 50 ± 1 | 55 ± 5 | -13 ± 5 | 8.1 ± 0.7 | 15.2 ± 6.3 | ND | ||||
| Meclofenamic | 66 ± 5 | 74 ± 4 | -30 ± 11 | 4.0 ± 0.7 | 5.9 ± 0.6 | 42.5 ± 6.7 | ||||
| Tolfenamic acid | 53 ± 5 | 60 ± 10 | -24 ± 21 | 5.6 ± 1.6 | 9.4 ± 1.6 | >100 | ||||
| Niflumic acid | 32 ± 4 | 38 ± 1 | -27 ± 13 | 4.3 ± 1.5 | 7.8 ± 2.9 | >100 | ||||
| Diflunisal | 90 ± 14 | 109 ± 14 | -24 ± 13 | 18.3 ± 9.9 | 14.5 ± 2.4 | >100 | ||||
| Olsalazine | 34 ± 8 | 44 ± 9 | 49 ± 11 | 37.6 ± 10.9 | 45.1 ± 9.5 | 36.0 ± 9.0 | ||||
β3, α1β3γ2s; β2, α1β2γ2s; β1, α1β1γ2s. ND, not determined.