Aminobutyric Acid

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7-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian CNS. GABA is primarily synthesized (Fig. 24.3) from glutamate by the enzyme l-glutamic acid-/-decarboxylase (GAD); it is subsequently transaminated with a-ketoglutarate by GABAA-oxoglutarate transaminase (GABA-T) to yield glutamate and succinic semialdehyde.

Two types of GABA receptors have been identified in mammals, a GABAA- and a GABAB-receptor. The GABAA-receptor (or recognition site), when coupled with GABA, induces a shift in membrane permeability, primarily to chloride ions, causing hyperpolarization of the neuron. This GABA receptor appears to be part of a macromolecule that contains, in addition to the GABAA-receptor, benzodiazepine and barbiturate binding sites and the chloride ionophore (chloride channel). See Figure 24.4.

A number of drugs are thought to exert their CNS effect by altering GABAA-receptor activity. The 1,4-benzodiazepines, (3-carbolines, barbiturates, alcohols, and general anesthetics appear to facilitate GABA transmission by interacting at this macromolecular complex. Vigabatrin, a newly approved anticonvulsant, elevates brain GABA by inhibiting the breakdown enzyme GABA-T. Several CNS convulsants, including bicuculline, picrotoxinin, and pentylenetetrazol, are antagonists at the GABA receptor. Since GABA agonists have been shown to be anticonvulsants and GABA antagonists are convulsants, there is much interest in the role of GABA in epilepsy (see Chapter 32). The GABAB-receptor, in contrast, is not modulated by ben-zodiazepines, is not linked to chloride movement, and is not nearly as well characterized as is the GABAA-re-ceptor. The GABAB-receptor is coupled to K+channels and is activated by the antispastic agent baclofen.

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Free Yourself from Panic Attacks

Free Yourself from Panic Attacks

With all the stresses and strains of modern living, panic attacks are become a common problem for many people. Panic attacks occur when the pressure we are living under starts to creep up and overwhelm us. Often it's a result of running on the treadmill of life and forgetting to watch the signs and symptoms of the effects of excessive stress on our bodies. Thankfully panic attacks are very treatable. Often it is just a matter of learning to recognize the symptoms and learn simple but effective techniques that help you release yourself from the crippling effects a panic attack can bring.

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