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Glycine Transporter 2
Sodium- and chloride-dependent glycine transporter 2, also known as glycine transporter 2 (GlyT2), is a protein that in humans is encoded by the ''SLC6A5'' gene. The glycine transporter 2 is a membrane protein which recaptures glycine, a major inhibitory transmitter in the spinal cord and brainstem. GlyT2 is a specific marker of glycinergic neurons and a member of the Na+ and Cl−-coupled transporter family SLC6. Glycine uptake mediated by GlyT2 is electrogenic, coupled to three Na+ and one Cl− (i.e. two positive charges per glycine). In humans, GlyT2 is encoded by the ''SLC6A5'' gene. Inactivation of GlyT2 in knockout mice is lethal during the second post-natal week as the absence of GlyT2 disrupts inhibitory transmission by reducing glycine release. Mutations in SLC6A5 gene are responsible for a presynaptic form of hyperekplexia, a genetic disease causing increased startle reflex. GlyT2 main physiological role is to recapture glycine released in the synaptic cleft and to main ...
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Protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, responding to stimuli, providing structure to cells and organisms, and transporting molecules from one location to another. Proteins differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in protein folding into a specific 3D structure that determines its activity. A linear chain of amino acid residues is called a polypeptide. A protein contains at least one long polypeptide. Short polypeptides, containing less than 20–30 residues, are rarely considered to be proteins and are commonly called peptides. The individual amino acid residues are bonded together by peptide bonds and adjacent amino acid residues. The sequence of amino acid residue ...
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Gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a basic unit of heredity and the molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protein-coding genes and noncoding genes. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes (many different genes) as well as gen ...
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Glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a ''Clostridium tetani'' infection) can cause spastic paralysis due to uninhibited muscle contraction. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. History and etymology Glycine was discovered in 1820 by the French chemist He ...
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Spinal Cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the spinal cord, which contains cerebrospinal fluid. The brain and spinal cord together make up the central nervous system (CNS). In humans, the spinal cord begins at the occipital bone, passing through the foramen magnum and then enters the spinal canal at the beginning of the cervical vertebrae. The spinal cord extends down to between the first and second lumbar vertebrae, where it ends. The enclosing bony vertebral column protects the relatively shorter spinal cord. It is around long in adult men and around long in adult women. The diameter of the spinal cord ranges from in the cervical and lumbar regions to in the thoracic area. The spinal cord functions primarily in the transmission of nerve signals from the motor cortex to the body, ...
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Brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is continuous with the thalamus of the diencephalon through the tentorial notch, and sometimes the diencephalon is included in the brainstem. The brainstem is very small, making up around only 2.6 percent of the brain's total weight. It has the critical roles of regulating cardiac, and respiratory function, helping to control heart rate and breathing rate. It also provides the main motor and sensory nerve supply to the face and neck via the cranial nerves. Ten pairs of cranial nerves come from the brainstem. Other roles include the regulation of the central nervous system and the body's sleep cycle. It is also of prime importance in the conveyance of motor and sensory pathways from the rest of the brain to the body, and from the body back to t ...
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Knockout
A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, muay thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, as well as fighting-based video games. A full knockout is considered any legal strike or combination thereof that renders an opponent unable to continue fighting. The term is often associated with a sudden traumatic loss of consciousness caused by a physical blow. Single powerful blows to the head (particularly the jawline and temple) can produce a cerebral concussion or a carotid sinus reflex with syncope and cause a sudden, dramatic KO. Body blows, particularly the liver punch, can cause progressive, debilitating pain that can also result in a KO. In boxing and kickboxing, a knockout is usually awarded when one participant falls to the canvas and is unable to rise to their feet within a specified period of time, typically because of ex ...
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Hyperekplexia
Hyperekplexia (; "exaggerated surprise") is a very rare neurologic disorder classically characterised by pronounced startle responses to tactile or acoustic stimuli and hypertonia. The hypertonia may be predominantly truncal, attenuated during sleep and less prominent after a year of age. Classic hyperekplexia is caused by genetic mutations in a number of different genes, all of which play an important role in glycine neurotransmission. Glycine is used by the central nervous system as an inhibitory neurotransmitter. Hyperekplexia is generally classified as a genetic disease, but some disorders can mimic the exaggerated startle of hyperekplexia. Signs and symptoms The three main signs of hyperekplexia are generalized stiffness, excessive startle beginning at birth and nocturnal myoclonus. Affected individuals are fully conscious during episodes of stiffness, which consist of forced closure of the eyes and an extension of the extremities followed by a period of generalised stiffn ...
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Startle
In animals, including humans, the startle response is a largely unconscious defensive response to sudden or threatening stimuli, such as sudden noise or sharp movement, and is associated with negative affect.Rammirez-Moreno, David. "A computational model for the modulation of the prepulse inhibition of the acoustic startle reflex". ''Biological Cybernetics'', 2012, p. 169 Usually the onset of the startle response is a startle reflex reaction. The startle reflex is a brainstem reflectory reaction (reflex) that serves to protect vulnerable parts, such as the back of the neck (whole-body startle) and the eyes (eyeblink) and facilitates escape from sudden stimuli. It is found across many different species, throughout all stages of life. A variety of responses may occur depending on the affected individual's emotional state, body posture, preparation for execution of a motor task, or other activities. The startle response is implicated in the formation of specific phobias. Startle ...
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Amoxapine
Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCAs). It is the N-demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States). Medical uses Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days. In excess of 80% of patients that do respond to amoxapine are reported to respond within two weeks of the beginning of treatment. It also has properties similar to those of the atypical antipsychotics, and may behave as one and may be used in the treatment of schizophrenia off-label. Despite its apparent lack of extrapyramidal side effects in patients with schizophrenia it has been found to exacerbate motor symptoms in patients with Parkinson's disease ...
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Alcohol (drug)
Alcohol, sometimes referred to by the chemical name ''ethanol'', is a depressant, depressant drug that is the active ingredient in alcoholic drink, drinks such as beer, wine, and distilled spirits (hard liquor). It is one of the oldest and most commonly consumed recreational drugs, causing the characteristic effects of alcohol intoxication ("drunkenness"). Among other effects, alcohol produces happiness and euphoria, anxiolytic, decreased anxiety, increased sociability, sedation, impairment of cognitive, memory, motor control, motor, and sense, sensory function, and generalized depression of central nervous system (CNS) function. Ethanol is only one of several types of Alcohol (chemistry), alcohol, but it is the only type of alcohol that is found in alcoholic beverages or commonly used for recreational purposes; other alcohols such as methanol and isopropyl alcohol are significantly more toxicity, toxic. A mild, brief exposure to isopropanol, being only moderately more toxic tha ...
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N-Arachidonylglycine
''N''-Arachidonylglycine (NAGly) is a carboxylic metabolite of the endocannabinoid anandamide (AEA). Since it was first synthesized in 1996, NAGly has been a primary focus of the relatively contemporary field of lipidomics due to its wide range of signaling targets in the brain, the immune system and throughout various other bodily systems. In combination with 2‐arachidonoyl glycerol (2‐AG), NAGly has enabled the identification of a family of lipids often referred to as endocannabinoids. Recently, NAGly has been found to bind to G-protein coupled receptor 18 (GPR18), the putative abnormal cannabidiol receptor. NaGly is an endogenous inhibitor of fatty acid amide hydrolase (FAAH) and thereby increases the ethanolamide endocannabinoids AEA, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) levels. NaGly is found throughout the body and research on its explicit functions is ongoing. Biosynthesis and degradation The biosynthesis and degradation of NaGly is not complete ...
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Opiranserin
Opiranserin (; developmental code name VVZ-149) is a selective and combined glycine GlyT2 transporter blocker ( = 0.86 μM), purine P2X3 receptor antagonist ( = 0.87 μM), and serotonin 5-HT2A receptor antagonist ( = 1.3 μM) which is under development by Vivozon for the intravenous treatment of postoperative pain. As of April 2017, it is in phase II clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...s for this indication. The of the drug was issued in 2017. References {{Serotonin receptor modulators 5-HT2A antagonists Dimethylamino compounds Analgesics Benzamides Experimental drugs Glycine reuptake inhibitors Receptor antagonists ...
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