**2.1 GABAA receptor**

Among the three types of GABA receptors, the GABAA receptor is the best characterized one. For several selective ligands, this channel has numerous binding sites. One class of therapeutic drugs linked to this target are receptor modulators: benzodiazepines, non-benzodiazepines and barbiturates, most of which improve the effect of GABA by increasing the chloride channel opening [13].

#### **Figure 1.**

*A. The subunits of GABAA receptor and chlorine channel. B. Represents the barbiturate and benzodiazepine binding sites on GABA receptor subunits.*

The GABAA agonist, muscimol, antagonist bicuculline and picrotoxin and inverse agonist FG 7142 are additional ligands which bind to the GABAA receptor. Some of these agents do not seem to have therapeutic benefits, but when used as pharmacological tools for the GABAA receptor they are the most significant ligands. Neuro-active steroids and partial benzodiazepine agonists (PBAs) are some newly discovered agents which are coming into recent considerations [14]. PBAs (e.g., bretazenil, imidazenil) are GABAA receptor activators, similar to benzodiazepines. Although they tend to have lower effectiveness compared to full benzodiazepine agonists, they give a more favorable side effect profile. Compared to other configurations found in more selective areas, this subtype is common throughout the brain [15].

## **2.2 GABAB receptor**

GABAB receptors have seven membrane-spanning amino acid domains which are connected by a G-protein to its signaling pathway (K+ , Ca++ ion channels or adenylate cyclase). Presynaptic GABAB receptors are majorly coupled to calcium channels and their stimulation by the receptor results in decrease of calcium conductance and decline of GABA release. Thus, the receptors auto-regulates the discharge of GABAA and gives the GABAA system with negative feedback. On the other hand, Post-synaptic GABAB receptors are primarily linked to potassium channels and their stimulation led to increased conductance of K<sup>+</sup> , hyperpolarization and decreased excitability of the neurons. The opening of T-type calcium channel is mainly associated with the actuation of GABAB receptor, resulting in calcium spiking activity that can contribute to absence seizure and is also included in signaling through the pathway of adenylate cyclase. It is therefore assumed that mediation of the GABAB receptor occurs through at least two distinct subtypes receptor [16–18].

### **2.3 GABAC receptor**

The GABAC receptor, a subtype of GABAA receptor characterization started when the analogue of GABA cis-4-aminocrotonic acid (CACA) in cat spinal interneurons developed a depressant action, which was not inhibited by the GABAA antagonist bicuculline and varied from the depressant actions of the GABAB agonist baclofen. The GABAC receptor is distinguished from both GABAA and GABAB by their pharmacological actions. GABAC is structurally different from GABAA because GABAC is hetero oligomeric and homo oligomeric which means it composed of many subunits of the same subtype, it can be either r1 or r2 [19].
