Gamma-aminobutyrate mechanism

Figure 1.2 Serotonin is one of the brain s neurotransmitters. This image depicts serotonin transmission between neurons and the drug Ecstasy s effects on that transmission. Serotonin is normally removed from the synapse shortly after being released. Ecstasy blocks this mechanism, increasing the amount of serotonin in the synapse. This causes the postsynaptic neuron to be overstimulated by serotonin. Serotonin is one of many neurotransmitters that nerve cells can secrete. Other common neurotransmitters include dopamine, glutamate, gamma aminobutyric acid (GABA), noradrenaline, and endorphins.

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. 

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. 

An interaction between G. biloba administered as 80 mg leaf extract twice a day and low-dose trazodone (20 mg twice daily) was suspected in a patient with Alzheimer s disease, who took the two products together. It is postulated that a pharmacodynamic (increased gamma-aminobutyric acid-ergic activity) and pharmacokinetic mechanisms [increased metabolism of trazodone to w-chlorophenylpiperazine (w -CPP), which acts on the benzodiazepine-binding sites and releases gamma-aminobutyric acid] contribute to the observed effect (32). Table 2 provides a list of reported pharmacodynamic and pharmacokinetic interactions involving ginkgo. 

Kumar S, Fleming RL, Morrow AL. Ethanol regulation of gamma-aminobutyric acid A receptors genomic and nongenomic mechanisms. Pharmacol Ther. 2004 101 211-226. 

Several neurochemical hypotheses have been set forth to explain the mechanisms leading to the clinical manifestations of anxiety disorders. Although a detailed account goes beyond the scope of this book, it is enough to state that norepinephrine, serotonin, and GABA (gamma-aminobutyric acid) are three of the neurotransmitters most often implicated. The medications found to be most useful for the treatment of anxiety disorders—SSRIs, TCAs, MAOIs, and benzodiazepines—have profound effects on these neurotransmitters and their respective neuroreceptors. 

Levy, L.J., Losowsky, M.S. Plasma gamma aminobutyric acid concentrations provide evidence of different mechanisms in the pathogenesis of hepatic encephalopathy in acute and chronic hver disease. Hepato-Gastroenterol. 1989 36 494-498... 

Ethanol is a central nervous system (CNS) depressant that initially and selectively depresses some of the most active portions of the brain (reticular activity system and cortex). The mechanism of action most likely involves interference with ion transport at the axonal cell membrane rather than at the synapse, similar to the action of other anesthetic agents. Ethanol can bind directly to the gamma-aminobutyric acid (GABA) receptor in the CNS and cause... 

Amobarbital, a barbiturate, is used as a sedative to treat insomnia and as a preanesthetic medication. The barbiturates were used extensively in the past as hypnotic-sedatives but have been replaced by the much safer benzodiazepine derivatives (see Table 9). They do continue to be used as anesthetics (e.g., thiopental) and anticonvulsants (e.g., phenobarbital). The primary mechanism of action of barbiturates is to increase inhibition through the gamma-aminobutyric acid (GABA) system (see Figure 50). Anesthetic barbiturates also decrease excitation via a decrease in calcium conductance. The most commonly used barbiturates are thiopental (Pentothal), methohexital (Brevital), secobarbital (Seconal), pentobarbital (Nembutal), amobarbital (Amytal), and phenobarbital (Luminal). 

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