A useful property of the many benzodiazepine site allosteric modulators is that they may display selective binding to particular subsets of receptors comprising specific subunits. This allows one to determine which GABA A receptor subunit combinations are prevalent in particular brain areas and provides a clue as to which subunit combinations may be responsible for behavioral effects of drugs acting at GABA A receptors. These selective ligands may have pharmacological advantages in that they may allow dissociation of desired therapeutic effects from undesirable side effects.  Few subtype selective ligands have gone into clinical use as yet, with the exception of zolpidem which is reasonably selective for α 1 , but several more selective compounds are in development such as the α 3 -selective drug adipiplon . There are many examples of subtype-selective compounds which are widely used in scientific research, including:
Synaptic Resilience through epigenetics
Epigenetic processes, the mechanisms by which specialized proteins turn genes on and off, play a critical role in learning and memory. Specifically, a chemical modification - histone acetylation (promoted by histone acetyltransferases, or HATs) - turns on (upregulates) genes important to brain cell function and stimulates the connections between neurons, called synapses. When this acetylation is reversed (de-acetylation) by protein complexes containing histone deacetylases (HDACs), these genes critical to learning and memory are turned down (downregulated).
In the mid 1980s, the neuroactive steroids 3α,5α-tetrahydroprogesterone or allopregnanolone (3α,5α-THP) and 3α,5α- tetrahydrodeoxycorticosterone (3α,5α-THDOC) were shown to modulate neuronal excitability via their interaction with GABA A receptors. The steroids 3α,5α-THP and 3α,5α-THDOC were able to enhance the GABA-elicited Cl − current.  In addition, these steroids might enhance the binding of muscimol and benzodiazepines to GABA A receptors.  Structure- activity studies (SAR) showed that the 3alpha-OH group is essential for the anesthetic actions of these steroids,  they also have an optimally-placed hydrogen bond accepting group on the β face of the steroid at the C-17 position. The four steroid rings form a rigid framework for positioning these hydrogen groups in three-dimensional space.  Analogues 5 and 6 (Figure 10) are weak modulators of GABA A receptor function because the flexible side chains in these analogues do not have the conformations required for high biological activity.