GABA

=What is Gamma-aminobutyric acid?= Gamma-aminobutyric acid is an amino acid and is also the chief inhibitory neurotransmitter in the central nervous system and retinas of human beings. It regulates muscle tone and various other functions. In most species, it is also considered a excitatory neurotransmitter. GABA can not be found in proteins, and while they can occasionally be found in pancreatic islet cells and the kidney, they are mosty absent from mammalian tissue of the nervous system. In spastic cerebral palsy, GABA absorption fails as a result of damaged rootlets. This leads to hypertonia.

=What are the functions of GABA?= In vertebrates, GABA acts at inhibitory synapses in the brain by binding to specific trensmembrane receptors in the plasma membrane of pre- and postsynaptic neurons. This causes the ion channels to open, which allows the flow of negatively-charged ions into the cell or positively-charged ions out of the cell. This action results in hyperpolorization. Three main types of GABA are known: Neurons that release GABA are called GABAergic neurons, and have mainly inhibitory action at receptors. However, in the hippocampus and neocortex, GABA has primarily excitatory effects earlier on in development, and is infact the major excitatory neurotransmitter in many areas of the brain. Whether it is excitatory or inhibitory depends on the direction and magnitude of the ionic currents controlled by the GABA A receptor. When directed towards the inside, GABA is excitatory. When directed outwards, GABA is inhibitory. A developmental switch in the molecular machinery which controls the polarity of the current is the reason for the functional changes of GABA between the neonatal and mature phases.
 * GABA A
 * GABA C ionotropic receptors - are ion channels themselves
 * GABA B metabotropic receptors - open ion channels using intermediaries

=Structure of Gaba= GABA is usually found as a zwitterion. This is the carboxyl group deprotonated and the amino group protonated. Its conformation usually depends upon its environment. In gas form, a highly folded conformation is favored due to the electrostatic attraction between the two functional groups. In the solid state, a more extended conformation is found. This would have a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is because of the packing interactions with the neighboring molecules. As a solution, five varying conformations can be found. The flexibility of GABA conformation is extremely important in its biological functioning. It has to bind to different receptors with different conformations.

=Synthesis= Organisms synthesize GABA from glutamate. They do this using the L-glutamic acid decarboxylase enzyme and pyridoxal phosphate as a cofactor. This process converts an excitatory GABA into an inhibitory GABA.

=GABA in Pharmacy= Gamma-aminobutyric acid was synthesized in 1883 for the first time, and was only regarded as a plant and microbe metabolic product. In the 1950's, they discovered GABA was an integral part of the mammalian central nervous system. Drugs that act as agonists of GABA receptors or increase the available amount of GABA cause a sort of relaxing effect. They also help settle anxiety and convulsion. Many of the substances also cause varying types of amnesia, as well. GABA has been purported to increase the amount of the human growth hormone, although the results of this study have been very rarely replicated. It is uncertain whether or not GABA can pass the blood-brain barrier. A few different types of these GABA affecting drugs would include: Drugs that affect it in a very different way would include:
 * [|avermectins]
 * [|muscimol]
 * [|Valerian extract]
 * [|progabide]
 * [|manganese]
 * [|benzodiazepines]
 * [|kavalactones]


 * [|tiagabine]—potentiates by inhibiting uptake into neurons and [|glia]
 * [|hyperforin]—inhibits the reuptake of GABA
 * [|tetanospasmin]—primary toxin of tetanus bacteria, blocks release of GABA
 * [|valproate]—potentiates by inhibiting GABA-T
 * [|vigabatrin]—potentiates by inhibiting GABA-T, preventing GABA breakdown