GABA Agonists: Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).Muscimol: A neurotoxic isoxazole isolated from species of AMANITA. It is obtained by decarboxylation of IBOTENIC ACID. Muscimol is a potent agonist of GABA-A RECEPTORS and is used mainly as an experimental tool in animal and tissue studies.GABA-A Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.GABA Antagonists: Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.Baclofen: A GAMMA-AMINOBUTYRIC ACID derivative that is a specific agonist of GABA-B RECEPTORS. It is used in the treatment of MUSCLE SPASTICITY, especially that due to SPINAL CORD INJURIES. Its therapeutic effects result from actions at spinal and supraspinal sites, generally the reduction of excitatory transmission.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.Bicuculline: An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.GABA-B Receptor Agonists: Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.Isoxazoles: Azoles with an OXYGEN and a NITROGEN next to each other at the 1,2 positions, in contrast to OXAZOLES that have nitrogens at the 1,3 positions.Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GAMMA-AMINOBUTYRIC ACID-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates.GABA Agents: Substances used for their pharmacological actions on GABAergic systems. GABAergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function.Microinjections: The injection of very small amounts of fluid, often with the aid of a microscope and microsyringes.GABA Modulators: Substances that do not act as agonists or antagonists but do affect the GAMMA-AMINOBUTYRIC ACID receptor-ionophore complex. GABA-A receptors (RECEPTORS, GABA-A) appear to have at least three allosteric sites at which modulators act: a site at which BENZODIAZEPINES act by increasing the opening frequency of GAMMA-AMINOBUTYRIC ACID-activated chloride channels; a site at which BARBITURATES act to prolong the duration of channel opening; and a site at which some steroids may act. GENERAL ANESTHETICS probably act at least partly by potentiating GABAergic responses, but they are not included here.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.GABA Plasma Membrane Transport Proteins: A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport.Dopamine Agonists: Drugs that bind to and activate dopamine receptors.Receptors, GABA-B: A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.GABA Uptake Inhibitors: Compounds that suppress or block the plasma membrane transport of GAMMA-AMINOBUTYRIC ACID by GABA PLASMA MEMBRANE TRANSPORT PROTEINS.GABA-A Receptor Antagonists: Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Purinergic P1 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P1 RECEPTORS.Nipecotic AcidsMuscarinic Agonists: Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.Nicotinic Agonists: Drugs that bind to and activate nicotinic cholinergic receptors (RECEPTORS, NICOTINIC). Nicotinic agonists act at postganglionic nicotinic receptors, at neuroeffector junctions in the peripheral nervous system, and at nicotinic receptors in the central nervous system. Agents that function as neuromuscular depolarizing blocking agents are included here because they activate nicotinic receptors, although they are used clinically to block nicotinic transmission.Adrenergic alpha-2 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-2 RECEPTORS.Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors.Serotonin 5-HT2 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT2 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT2 receptor subtypes.Phosphinic Acids: Inorganic or organic derivatives of phosphinic acid, H2PO(OH). They include phosphinates and phosphinic acid esters.Neural Inhibition: The function of opposing or restraining the excitation of neurons or their target excitable cells.Serotonin 5-HT1 Receptor Agonists: Endogenous compounds and drugs that specifically stimulate SEROTONIN 5-HT1 RECEPTORS. Included under this heading are agonists for one or more of the specific 5-HT1 receptor subtypes.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.GABA-B Receptor Antagonists: Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.Histamine Agonists: Drugs that bind to and activate histamine receptors. Although they have been suggested for a variety of clinical applications histamine agonists have so far been more widely used in research than therapeutically.Purinergic P2 Receptor Agonists: Compounds that bind to and stimulate PURINERGIC P2 RECEPTORS.Excitatory Amino Acid Agonists: Drugs that bind to and activate excitatory amino acid receptors.Adrenergic beta-Agonists: Drugs that selectively bind to and activate beta-adrenergic receptors.Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors.4-Aminobutyrate Transaminase: An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19.Synaptic Transmission: The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Adenosine A1 Receptor Agonists: Compounds that bind to and stimulate ADENOSINE A1 RECEPTORS.Inhibitory Postsynaptic Potentials: Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.Adrenergic alpha-Agonists: Drugs that selectively bind to and activate alpha adrenergic receptors.PyridazinesGlutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.Diazepam: A benzodiazepine with anticonvulsant, anxiolytic, sedative, muscle relaxant, and amnesic properties and a long duration of action. Its actions are mediated by enhancement of GAMMA-AMINOBUTYRIC ACID activity.Adrenergic alpha-1 Receptor Agonists: Compounds that bind to and activate ADRENERGIC ALPHA-1 RECEPTORS.Receptors, Opioid, mu: A class of opioid receptors recognized by its pharmacological profile. Mu opioid receptors bind, in decreasing order of affinity, endorphins, dynorphins, met-enkephalin, and leu-enkephalin. They have also been shown to be molecular receptors for morphine.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Hippocampus: A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.Cannabinoid Receptor Agonists: Compounds that interact with and stimulate the activity of CANNABINOID RECEPTORS.

*  Temporary inactivation of the dorsal entorhinal cortex impairs acquisition and retrieval of spatial information.

0/GABA Agonists; 0/Receptors, GABA-A; 2763-96-4/Muscimol From MEDLINE®/PubMed®, a database of the U.S. National Library of ... GABA Agonists / pharmacology. Male. Maze Learning / drug effects, physiology*. Mental Recall / drug effects, physiology*. ... Receptors, GABA-A / agonists, metabolism. Space Perception / drug effects, physiology*. Time Factors. ... In contrast, rats that received bilateral, intra-entorhinal infusions of muscimol, a gamma-aminobutyric acid(a) (GABA(a)) ...
biomedsearch.com/nih/Temporary-inactivation-dorsal-entorhinal-cortex/19800978.html

*  The anterior thalamus is critical for overcoming interference in a context-dependent odor discrimination task.

GABA-A Receptor Agonists / pharmacology. Hippocampus / drug effects, physiology*. Male. Muscimol / pharmacology. Odors. ...
biomedsearch.com/nih/anterior-thalamus-critical-overcoming-interference/23025833.html

*  gamma-Hydroxybutyric acid - Wikipedia

... they are GABAA agonists whereas GHB is primarily a GABAB agonist, and so do not worsen CNS depression as much as might be ... GHB is an agonist at the newly characterized GHB receptor, which is excitatory,[86][87] and it is a weak agonist at the GABAB ... Higher concentrations inhibit dopamine release via GABA(B) receptors as do other GABA(B) agonists such as baclofen and phenibut ... agonists.[92]. Activation of both the GHB receptor and GABA(B) is responsible for the addictive profile of GHB. GHB's effect on ...
https://en.wikipedia.org/wiki/Gamma-hydroxybutyric_acid

*  Publication List for for Richard Tham

Effects of the GABA agonists baclofen and THIP on long-term compensation in hemilabyrinthectomised rats. Brain Research, 1998, ... The GABA-b antagonist CGP 36742 has decompensatory effects on vestibulo-oculomotor behaviour in pigmented rats with a ... GABAB receptors contribute to vestibular compensation after unilateral labyrinthectomy in pigmented rats. Experimental Brain ... Early compensation of vestibulo-oculomotor symptoms after unilateral vestibular loss in rats is related to GABAB receptor ...
ep.liu.se/PubList/Default.aspx?userid=ricth61

*  NCI Drug Dictionary - National Cancer Institute

Baclofen acts as a gamma-aminobutyric acid (GABA) agonist specific for GABA-B receptors in the central nervous system (CNS). At ... The gamma-aminobutyric acid (GABA) analogue baclofen appears to activate the inhibitory GABA(B) receptor, a G protein-coupled ... Stimulation of GABA(B) receptor activity, modulation of Glu receptor activity, and inhibition of NMDA receptor activity may be ... Bazedoxifene functions as an estrogen agonist in lipid metabolism, thereby decreasing total and LDL cholesterol levels. In bone ...
https://cancer.gov/publications/dictionaries/cancer-drug?expand=B

*  The GABA Paradox - Waagepetersen - 2002 - Journal of Neurochemistry - Wiley Online Library

Belhage B., Meier E., Schousboe A. (1986) GABA-agonists induce the formation of low-affinity GABA-receptors on cultured ... Abbreviations used : GABA, γ-aminobutyrate ; GABA-T, GABA-aminotransferase ; GAD, glutamate decarboxylase ; GVG, γ-vinyl GABA ... Hassel B., Johannessen C.U., Sonnewald U., Fonnum F. (1998) Quantification of the GABA shunt and the importance of the GABA ... McGeer E.G., McGeer P.L., Thompson S. (1983) GABA and glutamate enzymes, inGlutamine, Glutamate and GABA in the Central Nervous ...
onlinelibrary.wiley.com/doi/10.1046/j.1471-4159.1999.0731335.x/references

*  Differing leukocyte gene expression profiles associated with fatigue in patients with prostate cancer versus chronic fatigue...

DBI is a natural GABA-A inverse agonist, that is, it produces the opposite effects of anxiolytics (e.g. Valium). Subjects ... Certain steroids, among which is DHEA, the precursor to estrogen, bind to GABA-A receptors, producing effects similar to ... Correlations with fatigue severity were similar in PCF and CFS for only DBI, the GABA-A receptor modulator (r=-0.50, p,0.005 ...
prohealth.com/library/showArticle.cfm?fontSize=large&libid=18413

*  Plus it

SO is a GABA agonist acting via GABAB receptors and although it also binds to γ-hydroxybutarate receptors, this pharmacologic ... Using zolpidem (Ambien), a short-acting GABAA agonist hypnotic, we show increased sleep spindle density and decreased REM sleep ... ZOL is a positive allosteric modulator at GABAA receptors with a short half-life (1.5-4.5 h), and rapid onset (mean Tmax = 1.6 ... 2005) Variations on an inhibitory theme: phasic and tonic activation of GABA(A) receptors. Nat Rev Neurosci 6:215-229. ...
jneurosci.org/content/33/10/4494

*  b12 en stikstof (NO)

GABA agonists-GABA acts as an inhibitory neurotransmitter to lower NMDA activity-these include the drug neurotin (gabapentin) ... Vitamin B6-balance glutamate and GABA levels, lowers excitotoxicity Niacin-role in energy metabolism Riboflavin-important in ... Pyridoxal phosphate-improves glutamate/GABA ratio Folic acid-lowers uncoupling of nitric oxide synthases ... improves balance between glutamate and GABA, lowers excitotoxicity Vitamin B12 in the form of cyanocobalamin-cyanocobalamin is ...
leefbewust.com/themas/b12_stikstof.html

*  2M Grant Launches Autism Personalized Medicine Effort | GEN

Arbaclofen is an oral selective gamma-amino butyric acid type B (GABA-B) receptor agonist designed to improve social and ...
genengnews.com/gen-news-highlights/2m-grant-launches-autism-personalized-medicine-effort/81247713?kwrd=Personalized Medicine

FasoracetamPivagabineOrg 20599BicucullineIsoxazolePicrotoxinHSD2 neurons: HSD2 neurons are a small group of neurons in the brainstem which are uniquely sensitive to the mineralocorticosteroid hormone aldosterone, through expression of HSD11B2. They are located within the caudal medulla oblongata, in the nucleus of the solitary tract (NTS).GABA transporter: GABA transporters are neurotransmitter transporters including:TalipexoleConcentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.N6-CyclopentyladenosineNipecotic acid: Nipecotic acid is a GABA reuptake inhibitor used in scientific research.SIB-1553ABeta1-adrenergic agonist: Beta1-adrenergic agonists, also known as Beta1-adrenergic receptor agonists, are a class of drugs that bind selectively to the beta-1 adrenergic receptor. As a result, they act more selectively upon the heart.NelotanserinLesogaberanPatch clamp: The patch clamp technique is a laboratory technique in electrophysiology that allows the study of single or multiple ion channels in cells. The technique can be applied to a wide variety of cells, but is especially useful in the study of excitable cells such as neurons, cardiomyocytes, muscle fibers, and pancreatic beta cells.AmthamineLong-acting beta-adrenoceptor agonist: Long-acting beta-adrenoceptor agonists (LABAs, more specifically β2-agonists) are usually prescribed for moderate to severe persistent asthma patients or patients with chronic obstructive pulmonary disease (COPD). They are designed to reduce the need for shorter-acting β2-agonists such as salbutamol, as they have a duration of action of approximately 12 hours in comparison with the 4- to 6-hour duration of salbutamol, making them candidates for sparing high doses of corticosteroids or treating nocturnal asthma and providing symptomatic improvement in patients with COPD.GABA transaminase inhibitor: A GABA transaminase inhibitor is an enzyme inhibitor that acts upon GABA transaminase.MivazerolEndralazineSC-17599Excitotoxicity: Excitotoxicity is the pathological process by which nerve cells are damaged or killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated by glutamatergic storm.Place cellPSN-375,963: PSN-375,963 is a selective ligand for the suggested novel cannabinoid receptor GPR119.

(1/1111) Neurite outgrowth-regulating properties of GABA and the effect of serum on mouse spinal cord neurons in culture.

Time-lapse photography was used to examine the effects of gamma-aminobutyric acid (GABA) on the outgrowth and motility of neurites in cultures from mouse spinal cord. GABA at concentrations of 100, 10 and 1 microM caused significant inhibition of neurite outgrowth and the motility of growth cones was significantly reduced by treatment with 100 and 10 microM GABA. This effect was mimicked by the GABA(B) receptor agonist baclofen, whereas the GABA(A) receptor agonist muscimol had no effect. The effect of GABA on outgrowth and motility seems to be dependent on the type of serum employed. The results reported here were obtained only when heat-inactivated serum was used and not when non heat-inactivated serum was added to the culture medium. They suggest that GABA has a role in the regulation of process outgrowth within the embryonic mouse spinal cord.  (+info)

(2/1111) Corticofugal amplification of facilitative auditory responses of subcortical combination-sensitive neurons in the mustached bat.

Recent studies on the bat's auditory system indicate that the corticofugal system mediates a highly focused positive feedback to physiologically "matched" subcortical neurons, and widespread lateral inhibition to physiologically "unmatched" subcortical neurons, to adjust and improve information processing. These findings have solved the controversy in physiological data, accumulated since 1962, of corticofugal effects on subcortical auditory neurons: inhibitory, excitatory, or both (an inhibitory effect is much more frequent than an excitatory effect). In the mustached bat, Pteronotus parnellii parnellii, the inferior colliculus, medial geniculate body, and auditory cortex each have "FM-FM" neurons, which are "combination-sensitive" and are tuned to specific time delays (echo delays) of echo FM components from the FM components of an emitted biosonar pulse. FM-FM neurons are more complex in response properties than cortical neurons which primarily respond to single tones. In the present study, we found that inactivation of the entire FM-FM area in the cortex, including neurons both physiologically matched and unmatched with subcortical FM-FM neurons, on the average reduced the facilitative responses to paired FM sounds by 82% for thalamic FM-FM neurons and by 66% for collicular FM-FM neurons. The corticofugal influence on the facilitative responses of subcortical combination-sensitive neurons is much larger than that on the excitatory responses of subcortical neurons primarily responding to single tones. Therefore we propose the hypothesis that, in general, the processing of complex sounds by combination-sensitive neurons more heavily depends on the corticofugal system than that by single-tone sensitive neurons.  (+info)

(3/1111) A single hydrophobic residue confers barbiturate sensitivity to gamma-aminobutyric acid type C receptor.

Barbiturate sensitivity was imparted to the human rho1 homooligomeric gamma-aminobutyric acid (GABA) receptor channel by mutation of a tryptophan residue at position 328 (Trp328), which is located within the third transmembrane domain. Substitutions of Trp328 with a spectrum of amino acids revealed that nearly all hydrophobic residues produced receptor channels that were both directly activated and modulated by pentobarbital with similar sensitivities. Previous studies with ligand-gated ion channels (including GABA) have demonstrated that even conservative amino acid substitution within the agonist-dependent activation domain (N-terminal extracellular domain) can markedly impair agonist sensitivity. Thus, the lack of significant variation in pentobarbital sensitivity among the Trp328 mutants attests to an intrinsic difference between pentobarbital- and the GABA-dependent activation domain. Compared with the heterooligomeric alphabetagamma receptor channel, the mode of modulation for homooligomeric Trp328 mutants by pentobarbital was more dependent on the GABA concentration, yielding potentiation only at low concentrations of GABA (fractions of their respective EC50 values), yet causing inhibition at higher concentrations. Agonist-related studies have also demonstrated that residue 328 plays an important role in agonist-dependent activation, suggesting a functional interconnection between the GABA and pentobarbital activation domains.  (+info)

(4/1111) Selective pruning of more active afferents when cat visual cortex is pharmacologically inhibited.

Activity-dependent competition is thought to guide the normal development of specific patterns of neural connections. Such competition generally favors more active inputs, making them larger and stronger, while less active inputs become smaller and weaker. We pharmacologically inhibited the activity of visual cortical cells and measured the three-dimensional structure of inputs serving the two eyes when one eye was occluded. The more active inputs serving the open eye actually became smaller than the deprived inputs from the occluded eye, which were similar to those in normal animals. These findings demonstrate in vivo that it is not the amount of afferent activity but the correlation between cortical and afferent activity that regulates the growth or retraction of these inputs.  (+info)

(5/1111) Carbamazepine facilitates effects of GABA on rat hippocampus slices.

AIM: To study the influence of carbamazepine (Car) on GABA effect in hippocampus. METHODS: Evoked potentials were recorded on pyramidal cells in CA1 after stimulation (0.5 Hz, 50 microseconds) to Schaffer collaterals in rat hippocampal slices (350 microns). RESULTS: Car 0.1 and 0.2 mmol.L-1 did not affect field potentials, whereas Car 0.2 mmol.L-1 plus GABA (0.1-1 mmol.L-1) gave rise to a stronger inhibition on field potentials than that of GABA alone. Bicuculline did not reverse Car facilitation on GABA inhibition on field potentials. (-)-Baclofen was more effective in inhibiting field potentials than GABA. Car 0.2 mmol.L-1 plus (-)-baclofen (1-5 mumol.L-1) brought an inhibition stronger than that of (-)-baclofen alone. CONCLUSION: Car facilitates the effects of GABA on pyramidal cells in hippocampal CA1 region, probably related to GABAB receptors.  (+info)

(6/1111) The role of gamma-hydroxybutyric acid in the treatment of alcoholism: from animal to clinical studies.

Since its discovery nearly 40 years ago, gamma-hydroxybutyric acid (GHB) has attracted several waves of scientific interest due to new developments in the knowledge of its mechanisms of action and ideas for its potential use in clinical practice. Its effects have been claimed to treat different psychiatric conditions, but over time its use has become limited to a few specific situations (e.g. sedating patients in non-painful surgical procedures and narcolepsy). New interest in the drug derives from its potential use in the treatment of alcoholism. Recent studies demonstrated a marked effect of the substance in suppressing ethanol (ETOH) withdrawal symptoms and in reducing craving for alcohol, compared to other available drugs. However, GHB has to be given under very careful supervision because of its side-effects, including the risk of abuse and dependence and possible interference with the metabolic pathways of endogenous GHB and ETOH. This short review discusses these and related issues and we hope that it will stimulate further interest in GHB.  (+info)

(7/1111) Tonic activation of presynaptic GABAB receptors in the opener neuromuscular junction of crayfish.

Release of excitatory transmitter from boutons on crayfish nerve terminals was inhibited by (R,S)-baclofen, an agonist at GABAB receptors. Baclofen had no postsynaptic actions as it reduced quantal content without affecting quantal amplitude. The effect of baclofen increased with concentration producing 18% inhibition at 10 microM; EC50, 50% inhibition at 30 microM; maximal inhibition, 85% at 100 microM and higher. There was no desensitization, even with 200 or 320 microM baclofen. Phaclofen, an antagonist at GABAB receptors, competitively antagonized the inhibitory action of baclofen (KD = 50 microM, equivalent to a pA2 = 4.3 +/- 0.1). Phaclofen on its own at concentrations below 200 microM had no effect on release, whereas at 200 microM phaclofen itself increased the control level of release by 60%, as did 2-hydroxy-saclofen (200 microM), another antagonist at GABAB receptors. This increase was evidently due to antagonism of a persistent level of GABA in the synaptic cleft, since the effect was abolished by destruction of the presynaptic inhibitory fiber, using intra-axonal pronase. We conclude that presynaptic GABAB receptors, with a pharmacological profile similar to that of mammalian GABAB receptors, are involved in the control of transmitter release at the crayfish neuromuscular junction.  (+info)

(8/1111) Inhibitory nature of tiagabine-augmented GABAA receptor-mediated depolarizing responses in hippocampal pyramidal cells.

Tiagabine is a potent GABA uptake inhibitor with demonstrated anticonvulsant activity. GABA uptake inhibitors are believed to produce their anticonvulsant effects by prolonging the postsynaptic actions of GABA, released during episodes of neuronal hyperexcitability. However, tiagabine has recently been reported to facilitate the depolarizing actions of GABA in the CNS of adult rats following the stimulation of inhibitory pathways at a frequency (100 Hz) intended to mimic interneuronal activation during epileptiform activity. In the present study, we performed extracellular and whole cell recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the functional consequences of tiagabine-augmented GABA-mediated depolarizing responses. Orthodromic population spikes (PSs), elicited from the stratum radiatum, were inhibited following the activation of recurrent inhibitory pathways by antidromic conditioning stimulation of the alveus, which consisted of either a single stimulus or a train of stimuli delivered at high-frequency (100 Hz, 200 ms). The inhibition of orthodromic PSs produced by high-frequency conditioning stimulation (HFS), which was always of much greater strength and duration than that produced by a single conditioning stimulus, was greatly enhanced following the bath application of tiagabine (2-100 microM). Thus, in the presence of tiagabine (20 microM), orthodromic PSs, evoked 200 and 800 ms following HFS, were inhibited to 7.8 +/- 2.6% (mean +/- SE) and 34.4 +/- 18.5% of their unconditioned amplitudes compared with only 35.4 +/- 12.7% and 98.8 +/- 12.4% in control. Whole cell recordings revealed that the bath application of tiagabine (20 microM) either caused the appearance or greatly enhanced the amplitude of GABA-mediated depolarizing responses (DR). Excitatory postsynaptic potentials (EPSPs) evoked from stratum radiatum at time points that coincided with the DR were inhibited to below the threshold for action-potential firing. Independently of the stimulus intensity with which they were evoked, the charge transferred to the soma by excitatory postsynaptic currents (EPSCs), elicited in the presence of tiagabine (20 microM) during the large (1,428 +/- 331 pA) inward currents that underlie the DRs, was decreased on the average by 90.8 +/- 1.7%. Such inhibition occurred despite the presence of the GABAB receptor antagonist, CGP 52 432 (10 microM), indicating that GABAB heteroreceptors, located on glutamatergic terminals, do not mediate the observed reduction in the amplitude of excitatory postsynaptic responses. The present results suggest that despite facilitating the induction of GABA-mediated depolarizations, tiagabine application may nevertheless increase the effectiveness of synaptic inhibition during the synchronous high-frequency activation of inhibitory interneurons by enhanced shunting.  (+info)



Receptors


  • Baclofen acts as a gamma-aminobutyric acid (GABA) agonist specific for GABA-B receptors in the central nervous system (CNS). (cancer.gov)
  • Belhage B. , Meier E. , Schousboe A. ( 1986 ) GABA-agonists induce the formation of low-affinity GABA-receptors on cultured cerebellar granule cells via preexisting high affinity GABA-receptors. (wiley.com)
  • Certain steroids, among which is DHEA, the precursor to estrogen, bind to GABA-A receptors, producing effects similar to anxiolytics. (prohealth.com)
  • The assay method for agonist-induced stimulation of high-affinity GTPase activity was developed and applied to membranes prepared from rat brain, postmortem human brain, and human blood platelets to investigate the functional interaction between some receptors and their coupled G proteins. (nii.ac.jp)
  • Furthermore, it has been shown that activation of G proteins coupled with some receptors negatively coupled to adenylyl cyclase, especially GABA_B receptors, can be detected in frontal cortical membranes prepared from postmortem human brains. (nii.ac.jp)
  • TASK-1/-3 channel expression can compensate for the absence of GABA A receptors in GABA A α6 KO mice. (aspetjournals.org)
  • Furthermore, because inhalation anesthetics act partially through GABA A receptors, the up-regulation of GABA A receptor function in TASK-1 KO mice might mask TASK-1 channel's significance as a target for inhalation anesthetics. (aspetjournals.org)
  • to start with the GABA A receptors. (aspetjournals.org)
  • GABA A receptors are GABA-gated anion channels that produce fast (phasic) inhibition at central synapses and tonic inhibition (from ambient GABA) at extrasynaptic sites ( Farrant and Nusser, 2005 ). (aspetjournals.org)

gamma-amin


  • In contrast, rats that received bilateral, intra-entorhinal infusions of muscimol, a gamma-aminobutyric acid(a) (GABA(a)) agonist, before either training or testing spent equal amounts of time in the two arms, indicating that they failed to acquire and were unable to express this information. (biomedsearch.com)
  • When death is associated with GHB, it is sometimes in conjunction with other drugs, such as alcohol or benzodiazepine which influence the same neurotransmitter ( gamma-aminobutyric acid , GABA). (wikipedia.org)
  • The gamma-aminobutyric acid (GABA) analogue baclofen appears to activate the inhibitory GABA(B) receptor, a G protein-coupled receptor, which may result in hyperpolarization of the neuronal cell membrane and inhibition of neurotransmitter release. (cancer.gov)
  • Belhage B. , Hansen G.H. , Elster L. , Schousboe A. ( 1998 ) Effects of gamma-aminobutyric acid (GABA) on synaptogenesis and synaptic function. (wiley.com)
  • Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not modify GABA A or GABA B radioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. (nih.gov)

baclofen


  • Accordingly, following extinction from long-access methamphetamine self-administration, rats were bilaterally microinjected with either a combination of the GABA agonists baclofen/muscimol or vehicle (artificial cerebrospinal fluid) into the infralimbic or prelimbic subcompartments of the medial prefrontal cortex or into the shell or core subcompartments of the nucleus accumbens. (omicsonline.org)

glutamate


  • It is a precursor to GABA , glutamate, and glycine in certain brain areas, and it acts on the GHB receptor and it is a weak agonist at the GABA B receptor. (wikipedia.org)
  • Belhage B. , Hansen G.H. , Schousboe A. ( 1993 ) Depolarization by K + and glutamate activates different neurotransmitter release mechanisms in GABAergic neurons : vesicular versus non-vesicular release of GABA. (wiley.com)

benzodiazepines


  • GABA-agonists such as alcohol and benzodiazepines, opiates and stimulants all lead to lasting changes in learning, motivation and pleasure. (elementsbehavioralhealth.com)

selective


  • Arbaclofen is an oral selective gamma-amino butyric acid type B (GABA-B) receptor agonist designed to improve social and communication functions in autism and Fragile X syndrome. (genengnews.com)
  • The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A alpha2,3 selective agonist, in comparison with lorazepam in healthy volunteers. (druglib.com)
  • Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers. (druglib.com)

pharmacology


  • Borden L.A. ( 1996 ) GABA transporter heterogeneity : pharmacology and cellular localization. (wiley.com)

1995


  • During M.J. , Ryder K.M. , Spencer D.D. ( 1995 ) Hippocampal GABA transporter function in temporal-lobe epilepsy. (wiley.com)
  • Chlormethiazole is a sedative, hypnotic, neuroprotective, and anticonvulsant agent with the ability to potentiate γ-aminobutyric acid (GABA)ergic neurotransmission through an allosteric modulation of the GABA A receptor complex (RC) ( Smith and Jewkes, 1995 ). (aspetjournals.org)

subunit


  • Carlson B.X. , Elster L. , Schousboe A. ( 1998 ) Pharmacological and functional implications of developmentally-regulated changes in GABA(A) receptor subunit expression in the cerebellum. (wiley.com)

Rats


  • Chapman A.G. & Evans M.C. ( 1983 ) Cortical GABA turnover during bicuculline seizures in rats. (wiley.com)

effects


  • Belhage B. , Hansen G.H. , Meier E. , Schousboe A. ( 1990 ) Effects of inhibitors of protein synthesis and intracellular transport on the γ-aminobutyric acid agonist-induced functional differentiation of cultured cerebellar granule cells. (wiley.com)
  • DBI is a natural GABA-A inverse agonist, that is, it produces the opposite effects of anxiolytics (e.g. (prohealth.com)
  • Thujone acts on GABA as an antagonist (opposite to the effects of alcohol) and as a component of several essential oils, is also used in perfumery. (wikipedia.org)

brain


  • Bernasconi R. , Maitre L. , Martin P. , Raschdorf F. ( 1982 ) The use of inhibitors of GABA-transaminase for the determination of GABA turnover in mouse brain regions : an evaluation of aminooxyacetic acid and gabaculine. (wiley.com)