GABA receptors complex

Buspirone. Buspirone (3) hydrochloride has been approved for the symptomatic management of generali2ed anxiety disorder (Table 3). This dmg is of special iaterest because it does not exert its therapeutic actions via modulation of the GABA receptor complex. This compound is stmcturaHy... 

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Saunders PA, Ho IK Barbiturates and the GABA receptor complex. Prog Drug Res 34 261-286, 1990... 

Harrison, NL and Simmonds, MA (1984) Modulation of the GABA receptor complex by a steroid anaesthetic. Brain Res. 323 287-292. 

Niles, L. (1991). Melatonin interaction with the benzodiazepine-GABA receptor complex in the CNS. Adv. Exp. Med. Biol. 294, 267-77. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

Zaleplon binds selectively to the brain omega- receptor situated on the alpha subunit of the GABA receptor complex and potentiates... 

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. 

Mediation of the anxiolytic-like action of benzodiazepines through the enhancement of GABAergic transmission at the GABA-A/benzodiazepine receptor complex is well known. Benzodiazepines act at the y-subunit of the GABA receptor complex to enhance chloride influx and thereby cause hyperpolarization of neurons. However, there is much less known about the role of intracellular signal transduction in the actions of benzodiazepines. 

Mechanism of Action A benzodiazepine that depresses all levels of the CNS, includ-ing limbic and reticular formation, by binding to benzodiazepine receptor sites on the gamma-aminobutyric acid (GABA) receptor complex. Modulates GABA, a major inhibitory neurotransmitter in the brain. Therapeutic Effect Produces anxiolytic effect,... 

Mechanism of Action Abarbiturate that binds at the GABA receptor complex, enhancing GABA activity. Therapeutic Effect Depresses central nervous system (CNS) activity and reticular activating system. 

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. 

Zolpidem and zaleplon are hypnotics that act at the omega-1 receptor of the central GABA receptor complex. This selectivity is hypothesized to be associated with a lower risk of dependence. Unlike benzodiazepines, zolpidem and zaleplon do not appear to have significant anxiolytic, muscle relaxant, or anticonvulsant properties. However, amnestic effects may occur. 

Eszopiclone is an additional hypnotic thought to act on GABA receptor complexes close to benzodiazepine receptors. No anxiolytic effect has been documented in the literature on this medication. 

These and other findings related to manipulation of the BZD-GABA-receptor complex indicate it is an important substrate in the neurobiological regulation of anxiety. Other systems also may play a role, however, including the noradrenergic and serotonergic systems, as well as a number of peptides and hormones ( 10). 

The Versatility of the Chloride Channel GABA Receptor Complex... 

Nonbenzodiazepine sedative-hypnotics. The non-BZD hypnotic zolpidem (Ambien) is a newer sleeping agent that is thought to work on more specific subdivisions of the GABA receptor complex than, for example, some of the older benzodiazepine agents. It is indicated for short-term insomnia and is generally limited to seven to 10 days of use. 

As far as is currently known, benzodiazepines and similar drugs (zopiclone, zolpidem) act by a single mechanism, interacting at the GABA receptor complex to enhance the ability of GABA to open a chloride ion channel and thereby hyperpolarize the neuronal membrane. It is usual, therefore, to classify benzodiazepines, and recommend their clinical use, on the basis of their duration of action or their half-life. While this is without doubt a useful classification, it is simplistic and does not take into account other important pharmacokinetic factors. 

Abecarnil is a partial agonist at the benzodiazepine -GABA receptor complex, and is used in generalized anxiety disorder. Its pharmacology suggests that it may be less likely to produce sedation and tolerance, but data thus far have not shown clear differences in its adverse effects from those of classical benzodiazepines, such as alprazolam, diazepam, and lorazepam. As expected, both acute adverse effects and tolerance are dose-related. 

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