Gamma-aminobutyrate action

Rudolph, U., Crestani, F., Benke, D., Brunig, I., Benson, J. A., Fritschy, J. M., et al. (1999) Benzodiazepine actions mediated by specific gamma-aminobutyric acid(A) receptor sub-types. Nature 401, 796-800. 

E Ng, G. Y., Bertrand, S., Sullivan, R., et al. (2001) Gamma-aminobutyric acid type B receptors with specific heterodimer composition and postsynaptic actions in hippocampal neurons are targets of anticonvulsant gabapentin action. Mol. Pharmacol. 59,144-152. 

White, H. S., Sarup, A., Bolvig, T., et al. (2002) Correlation between anticonvulsant activity and inhibitory action on glial gamma-aminobutyric acid uptake of the highly selective mouse gamma-aminobutyric acid transporter 1 inhibitor 3-hydroxy-4-amino-4,5,6,7-tetrahydro-l,2-benzisoxazole and its N-alkylated analogs. J. Pharmacol. Exp. Ther. 302, 636-644. 

Yunger, L. M., Fowler, P. J., Zarevics, P., and Seder, P. E. (1984) Novel inhibitors of gamma-aminobutyric acid (GABA) uptake anticonvulsant actions in rats and mice../. Pharmacol. Exp. Ther. 228,109-115. 

Abalis IM, Eldefrawi AT, Eldefrawi ME (1986) Actions of avermectin Bla on the gamma-aminobutyric acid receptor and chloride channels in rat brain. J Biochem Toxicol 1 69-82... 

So far attention has concentrated on the effects of lithium on excitatory transmitters. There is evidence that the drug can also facilitate inhibitory transmission, an effect that has been attributed to a desensitization of the pres)maptic gamma-aminobutyric acid (GABA) receptors, which results in an increase in the release of this inhibitory transmitter. The increased conversion of glutamate to GABA may also contribute to this process. Thus it would appear that lithium has a varied and complex action on central neurotransmission, the net result being a diminution in the activity of excitatory transmitters and an increase in GABAergic function. 

In essence, all of the older benzodiazepines that are structurally related to chlordiazepoxide and diazepam are termed 1,4-benzodiazepines. The chemical structure of some commonly used benzodiazepines is shown in Figure 9.2. They enhance the actions of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brain. As a consequence, they affect the activities of the cerebellum (concerned with balance and coordination), the limbic areas of the brain and the cerebral cortex (thought and decision making, fine movement control). 

Pharmacology Eszopiclone is a nonbenzodiazepine hypnotic. The precise mechanism of action of eszopiclone as a hypnotic is unknown, but its effect is believed to result from its interaction with gamma-aminobutyric acid (GABA)-receptor complexes at binding domains located close to or allosterically coupled to benzodiazepine receptors. 

Although the mechanism of action is not established, its activity may be related to increased brain levels of gamma-aminobutyric acid (GABA). 

The mechanism of action of acamprosate in the maintenance of alcohol abstinence is not completely understood. Chronic alcohol exposure is hypothesized to alter the normal balance between neuronal excitation and inhibition. Studies suggest acamprosate may interact with glutamate and gamma-aminobutyric acid (GABA) neurotransmitter systems centrally, and have led to the hypothesis that acamprosate restores this balance. 

Mechanism of Action An alcohol abuse deterrent that appears to interact with glutamate and gamma-aminobutyric acid neurotransmitter systems centrally, restoring their balance. Therapeutic Effect Reduces alcohol dependence. Pharmacokinetics Slowly absorbed from the G1 tract. Steady-state plasma concentrations are reached within 5 days. Does not undergo metabolism. Excreted in urine. Half-life 20-33 hr. 

Mechanism of Action A benzodiazepine that enhances the action of the inhibitory neurotransmitter gamma-aminobutyric acid in the brain. Therapeutic Effect Produces sedative effect from its CNS depressant action. 

Mechanism of Action A benzodiazepine that depresses all levels of the CNS by enhancing the action of gamma-aminobutyric acid, a major inhibitory neurotransmitter in the brain. Tircrapeutic Effect Produces anxiolytic effect, elevates the seizure threshold, produces skeletal muscle relaxation. 

Mechanism of Action A benzodiazepine that enhances action of gamma-aminobutyric acid (GABA) neurotransmission in the central nervous system (CNS). Therapeutic Effect Produces depressant effect at all levels of CNS. 

Mectianism of Action An antidote that antagonizes the effect of benzodiazepines on the gamma-aminobutyric acid receptor complex in the CNS. Therapeutic Effect Reverses sedative effect of benzodiazepines. 

Mechanism of Action An anticonvulsant and antineuralgic agent whose exact mechanism is unknown. May increase the synthesis or accumulation of gamma-aminobutyric acid by binding to as-yet-undefined receptor sites in brain tissue. Therapeutic Effect Reduces seizure activity and neuropathic pain. 

Mechanism of Action A barbiturate that enhances the activity of gamma-aminobutyric acid (GABA) by binding to the GABA receptor complex. Therapeutic Effect Depresses CNS activity. 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including metabolism of proteins, carbohydrates, and fats. Aids in the breakdown of glycogen and in the synthesis of gamma-aminobutyric acid in the CNS. Therapeutic Effect Prevents pyridoxine deficiency. Increases the excretion of certain drugs, such as iso-niazid, that are pyridoxine antagonists. 

Mechanism of Action An anticonvulsant that blocks repetitive, sustained firing of neurons by enhancing the ability of gamma-aminobutyric acid to induce an influx of chloride ions into the neurons may also block sodium channels. Therapeutic Effect Decreases seizure activity... 

Mechanism of Action An anticonvulsant that directly increases concentration of the inhibitory neurotransmitter gamma-aminobutyric acid. Therapeutic Effect Reduces seizure activity. 

Mechanism of Action A nonbenzodiazepine that enhances the action oftheinhibitory neurotransmitter gamma-aminobutyric acid. Therapeutic Effect Induces sleep and improves sleep quality. 

Siegwart R, Jurd R, Rudolph U Molecular determinants for the action of general anesthetics at recombinant alpha(2)beta(3) gamma(2)gamma-aminobutyric acid(A) receptors. J Neurochem 2002 80 140. [PMID 11796752]... 

Most of the CNS depressants have similar actions in the brain they enhance the actions of the neurotransmitter gamma-aminobutyric acid (GABA)— neurotransmitters are brain chemicals that facilitate communication between brain cells. GABA works by decreasing brain activity. Although different classes of CNS depressants work in unique ways, it is ultimately their common ability to increase GABA activity that produces a drowsy or calming effect. 

FIGURE 7-23. Shown here is an icon of valproic acid s pharmacologic actions. By interfering with calcium channels and sodium channels, valproate is thought both to enhance the inhibitory actions of gamma aminobutyric acid (GABA) and to reduce the excitatory actions of glutamate. 

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