GABA Potentiators

Neurosciences Newsletter on GABA GABA is a true neurotransmitter and is involved in many clinical conditions. These include anxiety disorders such as panic attacks, seizure disorders like epilepsy, and numerous other conditions including addiction, headaches, Parkinson's Syndrome, and cognitive impairment. GABA's role is that of the primary inhibitory neurotransmitter and functions by down-regulating neurotransmission. Neurons are electrically charge cells. Ion pumps actively transfer Na+ ions out of the neuron and a overall negative charged known as the cells resting potential is attained. Two opposing forces work to alter the neurons electrical potential. The neurotransmitter glutamate increases the flow of positively charged Na+ ions into the neuron and reduce the neurons electrical charge. If the electrical potential is reduced to a critical point , called the action potential, the neuron will fire. In contrast, the neurotransmitter GABA opposes the effects of glutamate and prevents the neuron from firing. GABA achieves this by effecting the actions of the GABA receptor, a 5 subunit ion transporter. When GABA binds to the GABA receptor, the subunits of the receptor "open" and there is an influx of chloride ions. This influx restores the electrical potential of the neuron and thereby decreases the likelihood that the neuron will depolarize and relay the incoming signal. Essentially, weak or irrelevant signals are more likely to be terminated or "ignored." GABA receptor and the putative binding site for a number of agents that affect GABA function. This diagram shows the GABA-A receptor and the putative binding site for a number of agents that affect GABA function. The GABA receptor is a relatively large molecule and has binding sites not only for GABA but also for many modulatory compounds. Many of these modulatory compounds are useful therapeutic agents. Positive GABA modulators, like the benzodiazepines, do not cause the ion channel to open and an influx of chloride ions to occur on their own. They only enhance the activity of naturally occurring GABA by potentiating its function and therefore have vastly reduced potential for overdose or side effects than receptor agonist compounds, like barbiturates. While much safer than barbiturates benzodiazepine use frequently leads to dependence and withdrawal syndrome effects. This limits their utility for mild/moderate symptoms as well as for long-term therapy. Because of the important role for GABA and positive GABA modulators NeuroScience has developed a number of products that address GABA and are beneficial for patients with GABA related disorders. The following ingredients have been found to increase GABA or have a positive GABA modulating effect and have been combined in specific amounts and ratios depending on the results of laboratory tests and the clinical application. Taurine Taurine is an amino acid that is present at significant levels in the CNS and is positive modulator of GABA that does not have any adverse side-effects. Taurine also potentiates glycine - the inhibitory neurotransmitter in the spinal cord. The role of taurine as an inhibitory amino acid has been confirmed in many studies. Not surprisingly, brain tissue and cardiac tissue, which are susceptible to high levels of neurotransmitter stimulation, maintain high levels of taurine. Taurine has been shown to prevent the neuronal damage that can occur when there is an exposure to increased levels of the excitatory neurotransmitter glutamate. Over stimulation by excitatory neurotransmitters is the primary cause of neuron death in ischemic stroke. Taurine has been found to significantly reduce neuron death caused by over stimulation. The calming effects of taurine have been well studied. Other studies of taurine have found that it can reduce epileptic seizures and that low taurine levels are associated with anxiety. Glutamine Significant quantities of glutamine are normally present in the brain to support the complex process of GABA synthesis. Glutamine is an amino acid and a common precursor for the biosynthesis of GABA and glutamate. Glutamine is transported into the presynaptic terminals of inhibitory neurons by the glutamine transporter (GlnT) and is catalyzed by the actions of the enzyme glutamine deaminase to form glutamate. Glutamate in turn is converted into GABA through the actions of glutamic acid decarboxylase (GAD). (NOTE: This biosynthetic route is somewhat more complex than originally thought. Some studies have demonstrated that the glutamate formed from glutamine may enter the tricarboxylic acid (TCA) cycle before being converted to GABA.) 5-HTP Serotonin is a neurotransmitter, or more correctly a neuromodulator, that is widely distributed throughout the brain and generally enhances GABA and therefore has inhibitory activity. Therefore, as a precursor to serotonin, 5-HTP can further increase the activity of GABA. Low serotonin levels are frequently an underlying component of many clinical conditions that are also related to GABA function, e.g. insomnia, depression, & anxiety. Neurotransmitter tests show that GABA needs serotonin to function properly. Normally, GABA increases and acts through a negative feedback mechanism to reduce elevated excitatory neurotransmitters. However, this feedback mechanism requires the neuromodulating effects of serotonin. This is evident in patients with symptoms related to low GABA who have adequate GABA levels but low serotonin. Theanine Theanine is another amino acid that affects GABA. Initial interest in theanine arose due to the seemingly paradoxical calming effect of a caffeine containing drink. Theanine is a naturally occurring amino acid present at significant levels in tea leaves and is the component responsible for this discord. Theanine has been found to alter glutamate transport and actually increase GABA levels. Further studies reveal that theanine reduces hypertension in models of hypertension, increases the effectiveness of some chemotherapy compounds, reduces the stimulatory effect of caffeine, and calms patients.