GABA

GABA is an endogenous ligand also referred to as  gamma-aminobutyric acid.  It is the major inhibitory neurotransmitter in the central nervous system.

GABA is a neurotransmitter that is the cornerstone of the inhibitory (calming) system of the body, and controls the action of epinephrine, norepinephrine and dopamine.  The main function of GABA is to prevent anxiety and stress-related messages from reaching the motor centers of the brain. They regulate excitability, including the seizure threshold. The brain must balance the excitatory and calming influences. Excessive excitation can lead to seizures, insomnia, anxiety and other clinical conditions; whereas excessive inhibition results in incoordination, sedation and anesthesia.

GABA does not penetrate the blood-brain barrier, but is synthesized in the brain from glutamate using the enzyme L-glutamic acid decarboxylase and pyridoxal phosphate, which is the active form of vitamin B6 as a cofactor via a metabolic pathway called the GABA shunt. This process converts glutamate, the principal excitatory neurotransmitter, into the principal inhibitory neurotransmitter (GABA).  This is why if you are deficient in the B6 vitamin you get over excitability symptoms, from irritability and twitching to seizures and epilepsy.

Drugs that act as agonists of GABA receptors  - known as GABA analogues or GABAergic drugs -  or increase the available amount of GABA typically have relaxing, anti-anxiety, and anti-convulsive effects.  Many of them cause anterograde amnesia and retrograde amnesia.

Although GABA activity tends to be confined to the brain, the central nervous system (CNS) effects then ripple out towards the autonomic nervous system (ANS)  - responsible for the autonomic regulation of internal organs and glands. The parasympathetic system controls the "rest-and-digest" activities that occur when the body is at rest, including sexual arousal,  salivation, lacrimation (tears), urination, digestion, and defecation. In contrast the sympathetic nervous system controls the stimulating activities associated with the fight-or-flight response.  So what happens in the CNS affects the ANS.

The parasympathetic nervous system uses chiefly acetylcholine (ACh) as its neurotransmitter, and acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. So here we see the links between these systems.  Furthermore,  as one would expect, the GABA system and the endocrine system with its neurotransmitters of adrenaline and norepinephrine are very closely linked – one is a nerve based system, the others are the blood based systems, but both do similar jobs.