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Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, especially for treatment-resistant depression and atypical depression. They are also used to treat panic disorder, social anxiety disorder, Parkinson's disease, and several other disorders.
Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches. They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures. They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.
Anticonvulsants are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain.
γ-Aminobutyric acid, or GABA, is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
Phenelzine, sold under the brand name Nardil, among others, is a non-selective and irreversible monoamine oxidase inhibitor (MAOI) of the hydrazine class which is primarily used as an antidepressant and anxiolytic. Along with tranylcypromine and isocarboxazid, phenelzine is one of the few non-selective and irreversible MAOIs still in widespread clinical use.
Vigabatrin, sold under the brand name Sabril, is a medication used to treat epilepsy. It became available as a generic medication in 2019.
Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It is given by mouth.
Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.
Branched-chain amino acid aminotransferase (BCAT), also known as branched-chain amino acid transaminase, is an aminotransferase enzyme (EC 2.6.1.42) which acts upon branched-chain amino acids (BCAAs). It is encoded by the BCAT2 gene in humans. The BCAT enzyme catalyzes the conversion of BCAAs and α-ketoglutarate into branched chain α-keto acids and glutamate.
A GABA receptor agonist is a drug that is an agonist for one or more of the GABA receptors, producing typically sedative effects, and may also cause other effects such as anxiolytic, anticonvulsant, and muscle relaxant effects. There are three receptors of the gamma-aminobutyric acid. The two receptors GABA-α and GABA-ρ are ion channels that are permeable to chloride ions which reduces neuronal excitability. The GABA-β receptor belongs to the class of G-Protein coupled receptors that inhibit adenylyl cyclase, therefore leading to decreased cyclic adenosine monophosphate (cAMP). GABA-α and GABA-ρ receptors produce sedative and hypnotic effects and have anti-convulsion properties. GABA-β receptors also produce sedative effects. Furthermore, they lead to changes in gene transcription.
In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:
In biochemistry, the glutamate–glutamine cycle is a cyclic metabolic pathway which maintains an adequate supply of the neurotransmitter glutamate in the central nervous system. Neurons are unable to synthesize either the excitatory neurotransmitter glutamate, or the inhibitory GABA from glucose. Discoveries of glutamate and glutamine pools within intercellular compartments led to suggestions of the glutamate–glutamine cycle working between neurons and astrocytes. The glutamate/GABA–glutamine cycle is a metabolic pathway that describes the release of either glutamate or GABA from neurons which is then taken up into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of either glutamate or GABA.
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. Gabaculine is also known as 3-amino-2,3-dihydrobenzoic acid hydrochloride and 5-amino cyclohexa-1,3 dienyl carboxylic acid. Gabaculine increased GABA levels in the brain and had an effect on convulsivity in mice.
Phenylethylidenehydrazine (PEH), also known as 2-phenylethylhydrazone or β-phenylethylidenehydrazine, is an inhibitor of the enzyme GABA transaminase (GABA-T). It is a metabolite of the antidepressant phenelzine and is responsible for its elevation of GABA concentrations. PEH may contribute to phenelzine's anxiolytic effects.
Aminooxyacetic acid, often abbreviated AOA or AOAA, is a compound that inhibits 4-aminobutyrate aminotransferase (GABA-T) activity in vitro and in vivo, leading to less gamma-aminobutyric acid (GABA) being broken down. Subsequently, the level of GABA is increased in tissues. At concentrations high enough to fully inhibit 4-aminobutyrate aminotransferase activity, aminooxyacetic acid is indicated as a useful tool to study regional GABA turnover in rats.
4-aminobutyrate---pyruvate transaminase is an enzyme with systematic name 4-aminobutanoate:pyruvate aminotransferase. This enzyme is a type of GABA transaminase, which degrades the neurotransmitter GABA. The enzyme catalyses the following chemical reaction
CI-966 (developmental code name) is a central nervous system depressant acting as a GABA reuptake inhibitor, specifically a highly potent and selective blocker of the GABA transporter 1 (GAT-1) (IC50 = 0.26 μM), and hence indirect and non-selective GABA receptor full agonist. It was investigated as a potential anticonvulsant, anxiolytic, and neuroprotective therapeutic but was discontinued during clinical development due to the incidence of severe adverse effects at higher doses and hence was never marketed.
Metadoxine, also known as pyridoxine-pyrrolidone carboxylate, is a drug used to treat chronic and acute alcohol intoxication. Metadoxine accelerates alcohol clearance from the blood.
4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene. This gene is located in chromosome 16 at position of 13.2. This gene goes by a number of names, including, GABA transaminase, GABAT, 4-aminobutyrate transaminase, NPD009 etc. This gene is mainly and abundant located in neuronal tissues. 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids. ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa. It is identified that almost tierce of human synapses have GABA. GABA is a neurotransmitter that has different roles in different regions of the central and peripheral nervous systems. It can be found also in some tissues that do not have neurons. In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA.
A GABA analogue is a compound which is an analogue or derivative of the neurotransmitter gamma-Aminobutyric acid (GABA).
References
- ↑ Ciesielski, L.; Simler, S.; Gensburger, C.; Mandel, P.; Taillandier, G.; Benoit-Guyod, J. L.; Boucherle, A.; Cohen-Addad, C.; Lajzerowicz, J. (1979). "GABA Transaminase Inhibitors". GABA—Biochemistry and CNS Functions. Advances in Experimental Medicine and Biology. Vol. 123. pp. 21–41. doi:10.1007/978-1-4899-5199-1_2. ISBN 978-1-4899-5201-1. PMID 390993.
- ↑ Bruni, J.; Wilder, B. J. (1979). "Valproic acid. Review of a new antiepileptic drug". Archives of Neurology. 36 (7): 393–398. doi:10.1001/archneur.1979.00500430023002. PMID 110294.
- ↑ Wang QP, Jammoul F, Duboc A, et al. (April 2008). "Treatment of epilepsy: the GABA-transaminase inhibitor, vigabatrin, induces neuronal plasticity in the mouse retina". Eur. J. Neurosci. 27 (8): 2177–87. doi:10.1111/j.1460-9568.2008.06175.x. PMC 2933832 . PMID 18412635.
- ↑ Gibson, J. P.; Yarrington, J. T.; Loudy, D. E.; Gerbig, C. G.; Hurst, G. H.; Newberne, J. W. (1990). "Chronic toxicity studies with vigabatrin, a GABA-transaminase inhibitor". Toxicologic Pathology. 18 (2): 225–238. doi: 10.1177/019262339001800201 . PMID 2399411.
- ↑ McKenna, K. F.; McManus, D. J.; Baker, G. B.; Coutts, R. T. (1994). "Chronic administration of the antidepressant phenelzine and its N-acetyl analogue: effects on GABAergic function". Journal of Neural Transmission. Supplementum. 41: 115–122. doi:10.1007/978-3-7091-9324-2_15. ISBN 978-3-211-82521-1. ISSN 0303-6995. PMID 7931216.
- ↑ Polc, P.; Pieri, L.; Bonetti, E. P.; Scherschlicht, R.; Moehler, H.; Kettler, R.; Burkard, W.; Haefely, W. (1986). "L-cycloserine: Behavioural and biochemical effects after single and repeated administration to mice, rats and cats". Neuropharmacology. 25 (4): 411–418. doi:10.1016/0028-3908(86)90236-4. PMID 3012401. S2CID 462885.