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.

Endogenous compounds and drugs that bind to and activate GAMMA-AMINOBUTYRIC ACID receptors (RECEPTORS, GABA).

Drugs that bind to but do not activate GABA RECEPTORS, thereby blocking the actions of endogenous GAMMA-AMINOBUTYRIC ACID and GABA RECEPTOR AGONISTS.

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.

The most common inhibitory neurotransmitter in the central nervous system.

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.

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.

A subset of GABA RECEPTORS that signal through their interaction with HETEROTRIMERIC G-PROTEINS.

Compounds that suppress or block the plasma membrane transport of GAMMA-AMINOBUTYRIC ACID by GABA PLASMA MEMBRANE TRANSPORT PROTEINS.

Endogenous compounds and drugs that bind to and activate GABA-A RECEPTORS.

Drugs that bind to but do not activate GABA-A RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-A RECEPTOR AGONISTS.

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.

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.

An isoquinoline alkaloid obtained from Dicentra cucullaria and other plants. It is a competitive antagonist for GABA-A receptors.

A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63)

Nipecotic acids are a class of compounds, specifically GABAergic drugs, that act as reversible inhibitors of the presynaptic GABA transporter (GAT), increasing the concentration of GABA in the synaptic cleft and enhancing its inhibitory effects on neurotransmission.

Endogenous compounds and drugs that bind to and activate GABA-B RECEPTORS.

Inorganic or organic derivatives of phosphinic acid, H2PO(OH). They include phosphinates and phosphinic acid esters.

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.

Drugs that bind to but do not activate GABA-B RECEPTORS thereby blocking the actions of endogenous or exogenous GABA-B RECEPTOR AGONISTS.

The function of opposing or restraining the excitation of neurons or their target excitable cells.

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.

The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.

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.

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.

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.

A pregnane found in the urine of pregnant women and sows. It has anesthetic, hypnotic, and sedative properties.

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.

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.

Hyperpolarization of membrane potentials at the SYNAPTIC MEMBRANES of target neurons during NEUROTRANSMISSION. They are local changes which diminish responsiveness to excitatory signals.

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.

**Pyridazine** is a heterocyclic organic compound, consisting of a six-membered ring containing two nitrogen atoms, which is a basic structure found in certain pharmaceuticals and natural compounds, though it does not have a specific medical definition itself as a component or condition.

Cyclic AMP response element modulator is a basic leucine zipper transcription factor that is regulated by CYCLIC AMP. It plays an important role in SPERMATID development in the mammalian TESTIS.

The relationship between the dose of an administered drug and the response of the organism to the drug.

A group of two-ring heterocyclic compounds consisting of a benzene ring fused to a diazepine ring.

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.

A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.

An analogue of GAMMA-AMINOBUTYRIC ACID. It is an irreversible inhibitor of 4-AMINOBUTYRATE TRANSAMINASE, the enzyme responsible for the catabolism of GAMMA-AMINOBUTYRIC ACID. (From Martindale The Extra Pharmacopoeia, 31st ed)

Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.

A benzodiazepine with pharmacologic actions similar to those of DIAZEPAM that can cause ANTEROGRADE AMNESIA. Some reports indicate that it is used as a date rape drug and suggest that it may precipitate violent behavior. The United States Government has banned the importation of this drug.

A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.

Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate via direct electrical coupling with ELECTRICAL SYNAPSES. Several other non-synaptic chemical or electric signal transmitting processes occur via extracellular mediated interactions.

The sodium salt of 4-hydroxybutyric acid. It is used for both induction and maintenance of ANESTHESIA.

Heterocyclic acids that are derivatives of 4-pyridinecarboxylic acid (isonicotinic acid).

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.

A potent benzodiazepine receptor antagonist. Since it reverses the sedative and other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses.

A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.

The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization).

A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.

Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.

Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.

Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.

Proteins involved in the transport of organic anions. They play an important role in the elimination of a variety of endogenous substances, xenobiotics and their metabolites from the body.

The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.

A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.

Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.