Figure 2.

Basmisanil is a potent and highly selective GABA_A-α5 receptor NAM. Data in the graphs are shown as mean (symbols) ± SEM (error bars). Error bars smaller than the symbol size are not shown. (a) Concentration–response curves of basmisanil in [³H]-flumazenil competition-binding assays to membranes expressing different human recombinant GABA_A receptor subtypes (n = 7–9 per concentration). (b) Concentration–response curves of the effects of basmisanil on ion current induced by an EC₁₀ of GABA in Xenopus oocytes (n = 7–8 per concentration). (c,d) Flumazenil antagonism of basmisanil effects. (c) Example recording of ion current from a voltage-clamped Xenopus oocyte expressing human GABA_A-α5. Two current traces are superimposed. The control response (black) was evoked by a GABA application in the absence of any modulators, as indicated by the black horizontal bar. During the test response (blue), after a delay, basmisanil and then flumazenil (blue horizontal bars) were added to GABA. (d) Bar graph showing flumazenil antagonism of the basmisanil effect. Green bars: flumazenil alone (30 nM: n = 5, 1000 nM: n = 11). Blue bars: flumazenil in presence of basmisanil (100 nM basmisanil: n = 16; basmisanil + flumazenil 30 nM: n = 6; basmisanil + flumazenil 1000 nM: n = 10).