γ-Aminobutyric acid (GABA) (IPA: [ˈgæmə əˈmiːnoʊbjuːˈtɪrɨk ˈæsɨd]) is the chief inhibitory
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
in the
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
ian
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
. It plays an important role in regulating
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
al excitability throughout the
nervous systemThe nervous system is a network of specialized cells that communicate information about an organism's surroundings and itself. It processes this information and causes reactions in other parts of the body. It is composed of neurons and other specialized cells called glial cells that aid in the...
. In humans, GABA is also directly responsible for the regulation of
muscle toneIn physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles. It helps maintain posture, and it declines during REM sleep...
. In
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
species GABA acts only on excitatory nerve receptors.
Although chemically it is an
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
, GABA is rarely referred to as such in the scientific or medical communities, because the term "amino acid," used without a qualifier, refers to the alpha amino acids, which GABA is not, nor is it incorporated into
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s.
In
spastic diplegiaSpastic diplegia, historically known as Little's Disease, is a form of cerebral palsy that is a neuromuscular condition of hypertonia and spasticity in the muscles of the lower extremities of the human body, usually those of the legs, hips and pelvis...
in humans, GABA absorption by some nerves becomes impaired, which leads to
hypertoniaHypertonia is an upper motor neuron dysfunction marked by an abnormal increase in tightness of muscle tone and a reduced ability of a muscle to stretch . Hypertonia is usually a feature of spasticity in particular muscles...
of the muscles signaled by those nerves.
In vertebrates, GABA acts at inhibitory
synapsesChemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
in the
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
by binding to specific transmembrane
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
s in the plasma membrane of both pre- and postsynaptic neuronal processes.
γ-Aminobutyric acid (GABA) (IPA: [ˈgæmə əˈmiːnoʊbjuːˈtɪrɨk ˈæsɨd]) is the chief inhibitory
neurotransmitterNeurotransmitters are endogenous chemicals which relay, amplify, and modulate signals between a neuron and another cell. Neurotransmitters are packaged into synaptic vesicles that cluster beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they...
in the
mammalMammals are a class of vertebrate animals whose females are characterized by the possession of mammary glands while both males and females are characterized by sweat glands, hair, three middle ear bones used in hearing, and a neocortex region in the brain.Mammals are divided into three main...
ian
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
. It plays an important role in regulating
neuronA neuron is an excitable cell in the nervous system that processes and transmits information by electrochemical signaling. Neurons are the core components of the brain, the vertebrate spinal cord, the invertebrate ventral nerve cord, and the peripheral nerves...
al excitability throughout the
nervous systemThe nervous system is a network of specialized cells that communicate information about an organism's surroundings and itself. It processes this information and causes reactions in other parts of the body. It is composed of neurons and other specialized cells called glial cells that aid in the...
. In humans, GABA is also directly responsible for the regulation of
muscle toneIn physiology, medicine, and anatomy, muscle tone is the continuous and passive partial contraction of the muscles. It helps maintain posture, and it declines during REM sleep...
. In
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
species GABA acts only on excitatory nerve receptors.
Although chemically it is an
amino acidAmino acids are molecules containing an amine group, a carboxylic acid group and one of the twenty R-groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H
2NCHRCOOH, where R is an organic substituent...
, GABA is rarely referred to as such in the scientific or medical communities, because the term "amino acid," used without a qualifier, refers to the alpha amino acids, which GABA is not, nor is it incorporated into
proteinProteins are organic compounds made of amino acids arranged in a linear chain and folded into a globular form. The amino acids in a polymer chain are joined together by the peptide bonds between the carboxyl and amino groups of adjacent amino acid residues...
s.
In
spastic diplegiaSpastic diplegia, historically known as Little's Disease, is a form of cerebral palsy that is a neuromuscular condition of hypertonia and spasticity in the muscles of the lower extremities of the human body, usually those of the legs, hips and pelvis...
in humans, GABA absorption by some nerves becomes impaired, which leads to
hypertoniaHypertonia is an upper motor neuron dysfunction marked by an abnormal increase in tightness of muscle tone and a reduced ability of a muscle to stretch . Hypertonia is usually a feature of spasticity in particular muscles...
of the muscles signaled by those nerves.
Neurotransmitter
In vertebrates, GABA acts at inhibitory
synapsesChemical synapses are specialized junctions through which neurons signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous system. They are crucial to the biological computations that underlie...
in the
brainThe brain is the center of the nervous system in all vertebrate, and most invertebrate, animals. Some primitive animals such as jellyfish and starfish have a decentralized nervous system without a brain, while sponges lack any nervous system at all...
by binding to specific transmembrane
receptorIn biochemistry, a receptor is a protein molecule, embedded in either the plasma membrane or cytoplasm of a cell, to which a mobile signaling molecule may attach...
s in the plasma membrane of both pre- and postsynaptic neuronal processes. This binding causes the opening of
ion channelIon channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s to allow the flow of either negatively charged
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
ions into the
cellThe cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of an organism that is classified as living, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos...
or positively charged
potassiumPotassium is the chemical element with the symbol K , atomic number 19, and atomic mass 39.0983. Potassium was first isolated from potash...
ions out of the cell. This action results in a negative change in the transmembrane potential, usually causing
hyperpolarizationHyperpolarization is a change in a cell's membrane potential that makes it more negative. It is the opposite of a depolarization.Hyperpolarization is often caused by efflux of K+ through K+ channels, or influx of Cl– through Cl– channels. On...
. Two general classes of
GABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
are known: GABA
A in which the receptor is part of a
ligand-gated ion channelLigand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...
complex, and GABA
B metabotropic receptorMetabotropic receptor is a subtype of membrane receptors at the surface or in vesicles of eukaryotic cells.In the nervous system, based on their structural and functional characteristics, neurotransmitter receptors can be classified into two broad categories: metabotropic and ionotropic receptors...
s, which are
G protein-coupled receptorG protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...
s that open or close ion channels via intermediaries (
G proteinG proteins, short for guanine nucleotide-binding proteins, are a family of proteins involved in second messenger cascades.G proteins are so called because they function as "molecular switches," alternating between an inactive guanosine diphosphate and active guanosine triphosphate bound state,...
s).
Neurons that produce GABA as their output are called GABAergic neurons, and have chiefly inhibitory action at receptors in the adult vertebrate.
Medium Spiny CellsThe medium spiny neurons are a special type of inhibitory cells representing approximately 90% of the neurons within the corpus striatum of the basal ganglia...
are a typical example of inhibitory
CNSThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
GABAergic cells. In contrast, GABA exhibits excitatory actions in
insectInsects are arthropods, having a hard exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae. They are the most diverse group of animals on the planet and include more than a million species that are already described. Insects represent more than half of all...
s, mediating
muscleMuscle is the contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
activation at synapses between
nerveA nerve is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
s and muscle cells, and also the stimulation of certain
glandA gland is an organ in an animal's body that synthesizes a substance for release such as hormones or breast milk, often into the bloodstream or into cavities inside the body or its outer surface .- Types :...
s. In mammals, some GABAergic neurons, such as
chandelier cellChandelier neurons or chandelier cells are a subset of GABA-ergic cortical interneurons. They are described as parvalbumin-containing and fast-spiking to distinguish them from other subtypes of GABAergic neurons. The name comes from the specific shape of their axon arbors, with the terminals...
s, are also able to excite their glutamatergic counterparts.
GABA
A receptors are chloride channels, that is, when activated by GABA, they allow the flow of
chlorideThe chloride ion is formed when the element chlorine picks up one electron to form an anion Cl
−...
ions across the membrane of the cell. Whether this chloride flow is excitatory/depolarizing (makes the voltage across the cell's membrane less negative), shunting (has no effect on the cell's membrane) or inhibitory/hyperpolarizing (makes the cell's membrane more negative) depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is excitatory or depolarizing; when the net chloride flows into the cell, GABA is inhibitory or hyperpolarizing. When the net flow of chloride is close to zero, the action of GABA is shunting. Shunting inhibition has no direct effect on the membrane potential of the cell, however it minimises the effect of any coincident synaptic input essentially by reducing the electrical resistance of the cell's membrane (essentially equivalent to
Ohm's lawIn electrical circuits, Ohm's law states that the current through a conductor between two points is directly proportional to the potential difference or voltage across the two points, and inversely proportional to the resistance between them....
). A developmental switch in the molecular machinery controlling concentration of chloride inside the cell and hence the direction of this ion flow, is responsible for the changes in the functional role of GABA between the neonatal and adult stages. That is to say, GABA's role changes from excitatory to inhibitory as the brain develops into adulthood.
Development
In
hippocampusThe hippocampus is a major component of the brains of humans and other mammals. It belongs to the limbic system and plays important roles in long-term memory and spatial navigation. Like the cerebral cortex, with which it is closely associated, it is a paired structure, with mirror-image halves in...
and
neocortexThe neocortex , also called the neopallium and isocortex , is a part of the brain of mammals. It is the outer layer of the cerebral hemispheres, and made up of six layers, labelled I to VI...
of the mammalian brain, GABA has primarily excitatory effects early in development, and is in fact the major excitatory neurotransmitter in many regions of the brain before the maturation of glutamate synapses -
See developing cortexThe study of neural development aims to describe the cellular basis of brain development and to address the underlying mechanisms. The field draws on both neuroscience and developmental biology to provide insight into the cellular and molecular mechanisms by which complex nervous systems develop...
.
In the developmental stages preceding the formation of synaptic contacts, GABA is synthesized by neurons and acts both as an autocrine (acting on the same cell) and paracrine (acting on nearby cells) signalling mediator.
GABA regulates the proliferation of neural
progenitor cellLike stem cells, progenitor cells have a capacity to differentiate into a specific type of cell. In contrast to stem cells, however, they are already far more specific: they are pushed to differentiate into their "target" cell...
s the migration and
differentiationIn developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a single zygote to a complex system of...
the elongation of
neuriteA neurite refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before...
s and the formation of synapses.
GABA also regulates the growth of
embryonicEmbryonic stem cells are pluripotent stem cells derived from the inner cell mass of the blastocyst, an early-stage embryo. Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells....
and neural stem cells. GABA can influence the development of neural progenitor cells via
brain-derived neurotrophic factorBrain-derived neurotrophic factor also known as BDNF is a protein which in humans is encoded by the BDNF gene. BDNF is a member of the "neurotrophin" family of growth factors – which are related to the canonical "Nerve Growth Factor", NGF...
(BDNF) expression. GABA activates the GABA
A receptor, causing cell cycle arrest in the S-phase, limiting growth.
Beyond the nervous system
In 2007, an excitatory GABAergic system was described in the airway
epitheliumIn biology and medicine, an epithelium is a tissue composed of cells that line the cavities and surfaces of structures throughout the body. Many glands are also formed from epithelial tissue...
. The system activates following exposure to allergens and may participate in the mechanisms of
asthmaAsthma is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. Asthma affects 7% of the population of the United States, and 300 million worldwide...
.
GABAergic system also has been found in the testis and in the eye lens.
Structure and conformation
GABA is found mostly as a
zwitterionA zwitterion is a chemical compound that carries a total net charge of 0 and is thus electrically neutral, but carries formal charges on different atoms....
, that is, with the carboxyl group deprotonated and the amino group protonated. Its
conformationIn chemistry, conformational isomerism is a form of stereoisomerism in which the isomers can be interconverted by rotations about formally single bonds.Such conformational isomers or conformers can rotate about one or more σ bonds...
depends on its environment. In the gas phase, a highly folded conformation is strongly favored because of the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to
quantum chemistryQuantum chemistry is a branch of theoretical chemistry, which applies quantum mechanics and quantum field theory to address issues and problems in chemistry. The description of the electronic behavior of atoms and molecules as pertaining to their reactivity is one of the applications of quantum...
calculations. In the solid state, a more extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended are found as a result of
solvationSolvation, also sometimes called dissolution, is the process of attraction and association of molecules of a solvent with molecules or ions of a solute...
effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.
History
Gamma-aminobutyric acid was first synthesized in 1883, and was first known only as a plant and microbe metabolic product. In 1950, however, GABA was discovered to be an integral part of the mammalian
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
.
Synthesis
Organisms synthesize GABA from glutamate using the
enzymeEnzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process are called substrates, and the enzyme converts them into different molecules, called the products. Almost all processes in a biological cell need enzymes to occur at...
L-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of vitamin B6) as a
cofactorCofactor may refer to any of the following:* Cofactor , the signed minor of a matrix* Minor , an alternative name for the determinant of a smaller matrix than that which it describes...
. This process converts glutamate, the principal
excitatoryExcitation or excitement can refer to:* The excited state of an atom* The excitation provided with an electrical generator or alternator* in ethology, provoking of the emotional state of excitement or agitation**Psychomotor agitation...
neurotransmitter, into the principal inhibitory neurotransmitter (GABA).
Pharmacology
Drugs that act as
agonistAn agonist is a drug that binds to a receptor of a cell and triggers a response by the cell. An agonist often mimics the action of a naturally occurring substance.An agonist produces an action...
s of
GABA receptorThe GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
s (known as GABA analogues or
GABAergic drugs) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. Many of the substances below are known to cause
anterograde amnesiaAnterograde amnesia is a loss of the ability to create memories after the event that caused the amnesia occurs. Anterograde amnesia and retrograde amnesia, where memories created prior to the event are lost, can occur together in the same patient...
and
retrograde amnesiaRetrograde amnesia is a form of amnesia where someone will be unable to recall events that occurred before the development of amnesia. The term is used to categorise patterns of symptoms, rather than to indicate a particular cause or etiology....
.
It has been suggested that orally administered GABA increases the amount of Human Growth Hormone, but this is questionable since it is unknown whether GABA can pass the
blood-brain barrierThe blood-brain barrier is a separation of circulating blood and cerebrospinal fluid maintained by the choroid plexus in the central nervous system . Endothelial cells restrict the diffusion of microscopic objects The blood-brain barrier (BBB) is a separation of circulating blood and...
. However, orally administered GABA does have effects outside of the
central nervous systemThe central nervous system is the part of the nervous system that functions to coordinate the activity of all parts of the bodies of bilaterian animals—that is, all animals more advanced than sponges or jellyfish. In vertebrates, the central nervous system is enclosed in the meninges. It contains...
(e.g. increased muscle tone).
GABAergic Drugs
GABAergic means to produce GABA.
- GABAA receptor ligands
- Agonists/Positive allosteric modulators: alcohol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug, best known as the type of alcohol found in alcoholic beverages and in modern thermometers. Ethanol is one of the oldest recreational drugs...
, barbiturateBarbiturates are drugs that act as central nervous system depressants, and, by virtue of this, they produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, hypnotics and as anticonvulsants. They have addiction potential, both physical and...
s, benzodiazepineA benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
s, carisoprodolCarisoprodol is a centrally-acting skeletal muscle relaxant. Carisoprodol is a colorless, crystalline powder, having a mild characteristic odor and a bitter taste. It is slightly soluble in water and freely soluble in alcohol, chloroform and acetone. Its solubility is practically independent of pH...
, etomidateEtomidate is a short acting intravenous anaesthetic agent used for the induction of general anaesthesia and for sedation for short procedures such as reduction of dislocated joints and cardioversion...
, glutethimideGlutethimide is a hypnotic sedative that was introduced in 1954 as a safe alternative to barbiturates to treat insomnia. Before long, however, it had become clear that glutethimide was just as likely to cause addiction and caused similarly severe withdrawal symptoms...
, L-theanine, kavaKava is an ancient crop of the western Pacific. Other names for kava include awa , 'ava , yaqona , and sakau . The word kava is used to refer both to the plant and the beverage produced from its roots...
, methaqualoneMethaqualone is a sedative drug that is similar in effect to barbiturates, a general CNS depressant. Its use peaked in the 1960s and 1970s as a hypnotic, for the treatment of insomnia, and as a sedative and muscle relaxant...
, muscimolMuscimol is the major psychoactive alkaloid present in many mushrooms of the Amanita genus. Unlike psilocybin, a tryptamine, muscimol is a potent, selective agonist of the GABA
A receptor.-Chemistry:...
, neuroactive steroidNeuroactive steroids rapidly alter neuronal excitability through interaction with neurotransmitter-gated ion channels. In addition, these steroids may also exert effects on gene expression via intracellular steroid hormone receptors...
s, nonbenzodiazepineThe nonbenzodiazepines, also called benzodiazepine-like drugs, are a class of psychoactive drugs whose pharmacological actions are similar to those of the benzodiazepines, but are structurally distant or unrelated to the benzodiazepines on a chemical level...
s, propofolPropofol is a short-acting, intravenously administered hypnotic agent. Its uses include the induction and maintenance of general anesthesia, sedation for mechanically ventilated adults, and procedural sedation. Propofol is also commonly used in veterinary medicine...
, scullcapScutellaria lateriflora, is a herbaceous plant also known as Blue skullcap, Hoodwort, Virginian skullcap, mad-dog skullcap is a hardy perennial herb native to North America. It is a member of the mint family Lamiaceae, which also includes many other herbs. The form is upright and is usually 0.2m...
, valerianValerian is a hardy perennial flowering plant, with heads of sweetly scented pink or white flowers. The flowers are in bloom in the northern hemisphere from June to September. Valerian was used as a perfume in the sixteenth century.Native to Europe and parts of Asia, Valerian has been introduced...
, volatileThe volatile anaesthetics are a class of general anaesthetic drugs. They share the property of being liquid at room temperature, but evaporating easily for administration by inhalation...
/inhaled anaestheticInhalational anaesthetics are gasses that possess anaesthetic qualities that are administered by breathing through an anaesthesia mask or ET tube connected to an anaesthetic machine. The agents of significant contemporary interest include the volatile anaesthetics and the gases ethylene, nitrous...
s.
- Antagonists/Negative allosteric modulators: bicuculline
Bicuculline is a light-sensitive competitive antagonist of GABA
A receptors. It was originally identified in 1932 in plant alkaloid extracts and has been isolated from Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and several Corydalis species. Since it blocks the inhibitory action...
, cicutoxinCicutoxin is a poisonous polyyne and alcohol found in various plants, most notably water hemlock . It is structurally related to the oenanthotoxin of hemlock water dropwort....
, flumazenilFlumazenil is a benzodiazepine antagonist....
, furosemideFurosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...
, gabazineGabazine is a drug that acts as an antagonist at GABA
A receptors. It is used in scientific research and has no role in medicine, as it would be expected to produce convulsions if used in humans....
, oenanthotoxinOenanthotoxin is a toxin extracted from hemlock water dropwort and other plants of the genus Oenanthe. It is a central nervous system poison, and acts as a noncompetitive gamma-aminobutyric acid antagonist. This toxin played some role in euthanasia in ancient Sardinia, for inducing risus...
, picrotoxinPicrotoxin, also known as cocculin, is a poisonous crystalline plant compound, first isolated by Boullay in 1812.Found primarily in Cocculus indicus and Anamirta cocculus, it has a strong physiological action. It acts as a noncompetitive antagonist for the GABA
A receptor...
, Ro15-4513Ro15-4513 is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in 1984, and is structurally related to the benzodiazepine antidote flumazenil.-Original development as alcohol antidote:...
, thujoneThujone is a ketone and a monoterpene that exists in two stereoisomeric forms: -3-thujone or α-thujone and -3-thujone or β-thujone. It has a menthol odor. Even though it is best known for being a chemical in absinthe, recent tests show absinthe contains only small quantities of thujone, and may or...
.
- GABAB Receptor Ligands
- Agonists: baclofen
Baclofen is a derivative of gamma-aminobutyric acid primarily used to treat spasticity.It is an agonist specific to mammalian but not fruit fly GABA
B receptors. Its beneficial effects result from actions at spinal and supraspinal sites. Baclofen can also be used to treat hiccups...
, GBLgamma-Butyrolactone is a hygroscopic colorless oily liquid with a weak characteristic odor and is soluble in water...
, GHBγ-Hydroxybutyric acid , also known as 4-hydroxybutanoic acid and sodium oxybate, is a naturally-occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also a neuroprotective therapeutic nutrient that is...
, phenibutBeta-phenyl-gamma-aminobutyric acid, better known as Phenibut or less commonly Fenibut or Phenybut, is natural derivative of the inhibitory neurotransmitter GABA . Sold as a dietary supplement in the US while in Russia sold as a neuropsychotropic drug that is capable of passing the blood-brain...
.
- Antagonists: phaclofen
Phaclofen, or phosphonobaclofen, is a selective antagonist for the GABA
B receptor....
, saclofenSaclofen is a competitive antagonist for the GABAB receptor. This drug is an analogue of the GABAB agonist Baclofen. The GABAB receptor is heptahelical receptor, expressed as an obligate heterodimer, which couples to the Gi/o class of heterotrimeric G-proteins...
.
- GABA reuptake inhibitor
A GABA reuptake inhibitor is a type of drug which acts as a reuptake inhibitor for the neurotransmitter gamma-Aminobutyric acid by blocking the action of the gamma-Aminobutyric acid transporters...
s: deramciclaneDeramciclane is a drug which acts as an antagonist at the 5HT2A receptor an inverse agonist at the 5HT2C receptor, and a GABA reuptake inhibitor...
, hyperforinHyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum .- Occurrence :...
, tiagabineTiagabine is an anti-convulsive medication produced by Cephalon and marketed under the brand name Gabitril. The drug was discovered at Novo Nordisk in Denmark in 1988 and was co-developed with Abbott. After a period of co-promotion, Cephalon licensed Tiagabine from Abbott/Novo and now is the...
.
- GABA-transaminase inhibitors: gabaculine
Gabaculine is a naturally occurring neurotoxin first isolated from the bacteria Streptomyces toyacaensis, which acts as a potent and irreversible GABA transaminase inhibitor, and also a GABA reuptake inhibitor....
, phenelzinePhenelzine is a psychoactive drug of the hydrazine chemical class which is used as an antidepressant and anxiolytic or antipanic agent. It acts as a nonselective and irreversible monoamine oxidase inhibitor...
, valproate, vigabatrinVigabatrin is an antiepileptic drugs that inhibits the catabolism of GABA by irreversibly inhibiting GABA transaminase. It is an analog of GABA, but it is not a receptor agonist. It is manufactured and distributed by Lundbeck Inc. . Lundbeck Inc. is a wholly owned subsidiary of H...
.
- GABA analogues: pregabalin
Pregabalin is an anticonvulsant drug used for neuropathic pain and as an adjunct therapy for partial seizures with or without secondary generalization in adults. It has also been found effective for generalized anxiety disorder and is approved for this use in the European Union. It was designed...
, gabapentinGabapentin is a GABA analogue. It was originally developed for the treatment of epilepsy, and currently, gabapentin is widely used to relieve pain, especially neuropathic pain.-Pharmacology:...
.
- Others: GABA (itself), L-glutamine, picamilon
Picamilon is a dietary supplement formed by combining niacin with GABA. It was developed in the Soviet Union in 1969 by the All-Union Scientific Research Institute and further studied in both Russia and Japan as a prodrug of GABA.Picamilon is sold in the United States as a dietary supplement,...
, progabideProgabide is an analog and prodrug of gamma-aminobutyric acid used in the treatment of epilepsy...
, tetanospasminTetanospasmin is the neurotoxin produced by the vegetative spore of Clostridium tetani in anaerobic conditions, causing tetanus. It has no known function for clostridia in the soil environment where they are normally encountered. It is sometimes called spasmogenic toxin, tetanus toxin or...
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