Pt. 3

As a neurotransmitter, GABA acts across the synaptic cleft, the junction between the presynaptic and postsynaptic neurons. On being released, GABA binds to special protein receptors to trigger inhibitory postsynaptic potential (IPSP). GABA receptors are classified into two subtypes: GABAA and GABAB receptors. GABAB receptors are metabotropic G-coupled receptors that regulate the slow component of inhibitory responses (Wu and Sun, 2015). In contrast, GABAA receptors are ionotropic ligand-gated chloride channels. In mammals, GABA­A receptors are Heteropentameric; they are composed of various combinations of 19 subunits: α1-6, β1-3, γ1-3, δ, ε, π, θ and ρ1-3 (Monesson-Olson et al., 2018). Different subunit compositions are differentially localized in the brain and have varying functionality (Wu and Sun, 2015). Mutations that affect GABAA receptors have been implicated in different forms of epilepsy. For instance, mutated α1 subunit of the GABAA receptor have been discovered in patients suffering from early infantile  epileptic encephalopathy, juvenile myoclonic epilepsy and other types of seizure disorders (reviewed by Braat and Kooy, 2015). As a result, many pharmacological compounds have been developed to target GABAA ­receptors, by binding allosteric sites. Nonetheless, even with the established anticonvulsant activity of these compounds, adverse side effects still emerge (Braat and Kooy, 2015).