The GABA(A) receptor plays a vital role in the mammalian brain and is responsible for a large majority of inhibitory neurotransmissions in the central nervous system (Perrine 144). The GABA(A) receptor is a member of the ionotropic (ligand gated) family of receptors that uses GABA, otherwise known as γ-aminobutyric acid, as its ligand. The binding of GABA to the receptor opens the associated ion channel, which in this case is selectively permeable to chlorine ions as they pass down their electrochemical gradient. The negatively charged chlorine ions passing into the cell further negate the postsynaptic membrane potential, usually hyperpolarizing it. This makes it more difficult to depolarize the cell and decreases the probability of further propagation of action potential.
[...] It was proven that the protein subunit was critical in the control of anxiety when an experiment done on lab rats, where or α5 subunits were taken away, showed that when treated with diazepam(valium) with the subunit missing the anxiolytic effects of the drug disappeared. Since benzodiazepine has a naturally occurring binding site on certain GABA(A) receptors, it can be concluded that there is a natural chemical in our bodies, of similar structure to benzodiazepine which utilizes these binding sites. [...]
[...] In an accidental scientific discovery the first of these benzodiazepine drugs, later to be named chlordiazepoxide, was found to have muscle relaxant properties and contain less toxins than the psychoactive drug of the time, chlorpromazine (Perrine 130). The new drug was sold on the market as Libirium in the early 1960's (Perrine 131). The success of Libirium prompted more research of these compounds by way of tagging of a methyl group onto amide nitrogen and the removal of the oxygen of nitrogen-oxide (Perrine 131). [...]
[...] And as it turns out, since benzodiazepines are receptor specific, their effect can be counteracted by a GABA antagonist(inhibitor), which will prevent further binding of GABA molecules to the receptor. Since the activity of benzodiazepines requires the binding of GABA, an antagonist such as flumazenil(Figure which can bind to the receptor without opening it, will keep the channel closed and thus preventing hyperpolarization and inhibition of the neuron. This can be very useful in the treatment of benzodiazepine overdose, which can be common among abusers of certain popular anti-depressant drugs. [...]
[...] Benzodiazepines work on receptors located in orbital frontal cortex, the amygdale and various part of the limbic system. It works in these areas specifically because these are the areas that deal with anxiety, circadian rhythm (which regulate sleep) and other responses to negative stimuli (Siegel). Benzodiazepines work by binding with an α subunit but the aforementioned two GABA ligands are still necessary for the ion channel to open. Therefore benzodiazepines can be seen as indirect agonists, also known as allosteric modulators. [...]
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