GABA 3 receptor

Benzodiazepines or barbiturates are helpful in the h eatment and prevention of seizures, and modulation of GABA receptors is beneficial in the treatment of anxiety disorders, insomnia and agitation—most likely due to a general inhibition of neuronal activity. 

The GABA receptor is insensitive to allosteric modulators, such as benzodiazepines and barbiturates. Native responses of the GABA receptor type occur in retinal bipolar or horizontal cells across vertebrate species. Although the term GABA receptors is still being used frequently they have been reassigned as part of GABA receptor family. 

In the peripheral nervous system, ACh is found as the neurotransmitter in the autonomic ganglia, the parasympathetic postganglionic synapse, and the neuromuscular endplate. Cholinergic neurons in the central nervous system are either wide ranging projection neurons or short ranging interneurons in (1) the basal forebrain (septum, diagonal band, nucleus basalis of Meynert) projects to the entire cortex, the hippocampus, 

ACh acts at two different types of cholinergic receptors Muscarinic and Nicotinic receptors. Muscarinic receptors (1) bind ACh as well as other agonists (muscarine, pilocarpine, bethan-echol) and antagonists (atropine, scopolamine). There are at least 5 different types of muscarinic receptors (M1-M5) and all have slow response times. They are coupled to G-proteins and a variety of second messenger systems. When activated, the final effect can be an opening or closing of channels for K , Ca , or Cl . Presynaptic cholinergic receptors are of the muscarinic or nicotinic type and can modulate the release of several neurotransmitters. 

Nicotinic receptors are less abundant then the muscarinic type in the CNS. They bind ACh as well as agonists such as nicotine and antagonists such as d-tubocurarine. The fast acting of the ionotropic nicotinic receptor allows an influx of mainly Na , followed by K , and Ca, into the cell. 

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Table 10. GABA and GABA Receptor Agonists and Antagonists...

Fig. 15. Drug binding sites associated with the GABA receptor—channel complex where (— -) represents the carbon backbone of GABA agonists.

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... 

Sleep and its modulation by N- and N,0-heterocyclic drugs that affect y-aminobutyric acid (GABA) receptor function 99AG(E)2852. 

Antiepileptics Na+, Ca2+ channels GABA receptors l Na+currents l Ca2+ currents GABA receptor activity l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters Sedation, dizziness, cognitive impairment, ataxia, hepatotoxicity, thrombocytopenia... 

GABA receptor modulators. These substances yield a potentatiation of synaptic responses to GABA by changing the affinity of the GABA receptor... 

GABA is the most prominent inhibitory neurotransmitter in the mammalian nervous system and acts via GABA receptors. Activation of GABAb receptors by GABA released from local spinal interneurons (Fig. 1) negatively modulates nociceptive transmission in the spinal cord. Agonists at GABAb receptors... 

Synaptic vesicles mediate the release of small molecules other than classical neurotransmitters and neuropeptides. Of these, zinc and ATP are the best characterized. NMDA and GABA receptors contain binding sites for zinc, and zinc exerts a direct effect on... 

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. 

Sanna E, Busonero F, Talani G, et al Comparison of the effects of zaleplom, zolpidem, and triazolam at various GABA, receptor subtypes. Eur J Pharmacol 431 103— 110, 2002... 

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

Dr. John E. Casida from the University of California Berkeley is inveshgating the fundamental basis for the selective toxicity of insecticides, including endosulfan, acting at the gamma-aminobutyric acid (GABA) receptor of mammals and insects. The research is sponsored by the National Institute of Environmental Health Sciences. 

Gant DB, Eldefrawi ME, Eldefrawi AT. 1987. Cyclodiene insecticides inhibit GABA receptor-regulated chloride transport. Toxicol Appl Pharmacol 88 313-321. 

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