|
Gaboxadol
Gaboxadol, also known as 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol (THIP), is a conformationally constrained derivative of the alkaloid muscimol that was first synthesized in 1977 by the Danish chemist Povl Krogsgaard-Larsen. In the early 1980s gaboxadol was the subject of a series of pilot studies that tested its efficacy as an analgesic and anxiolytic, as well as a treatment for tardive dyskinesia, Huntington's disease, Alzheimer's disease, and spasticity. It was not until 1996 that researchers attempted to harness gaboxadol's frequently reported sedative "adverse effect" for the treatment of insomnia, resulting in a series of clinical trials sponsored by Lundbeck and Merck. In March, 2007, Merck and Lundbeck cancelled work on the drug, citing safety concerns and the failure of an efficacy trial. It acts on the GABA system, but in a different way from benzodiazepines, Z-Drugs, and barbiturates. Lundbeck states that gaboxadol also increases deep sleep (stage 4). Unlike benzo ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABAA Receptor Agonists
The GABAA receptor (GABAAR) is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Upon opening, the GABAA receptor on the postsynaptic cell is selectively permeable to chloride ions (Cl−) and, to a lesser extent, bicarbonate ions (HCO3−). Depending on the membrane potential and the ionic concentration difference, this can result in ionic fluxes across the pore. If the membrane potential is higher than the equilibrium potential (also known as the reversal potential) for chloride ions, when the receptor is activated Cl− will flow into the cell. This causes an inhibitory effect on neurotransmission by diminishing the chance of a successful action potential occurring at the postsynaptic cell. The reversal potential of the GABAA-mediated inhibitory postsynaptic potential (IPSP) in normal solution is −70 mV, contrasting the GABAB IPSP (-100 mV). ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Muscimol
Muscimol (also known as agarin or pantherine) is one of the principal psychoactive constituents of ''Amanita muscaria'' and related species of mushroom. Muscimol is a potent and selective orthosteric agonist for the GABAA receptors and displays sedative-hypnotic, depressant and hallucinogenic psychoactivity. This colorless or white solid is classified as an isoxazole. Muscimol went under clinical trial phase I for epilepsy, but the trial was discontinued. Biochemistry Muscimol is one of the psychoactive compounds responsible for the effects of ''Amanita muscaria'' intoxication. Ibotenic acid, a neurotoxic secondary metabolite of ''Amanita muscaria'', serves as a prodrug to muscimol when the mushroom is ingested or dried, converting to muscimol via decarboxylation. Muscimol is produced in the mushrooms ''Amanita muscaria'' (fly agaric) and ''Amanita pantherina'', along with muscarine (which is present in trace amounts and it is not active), muscazone, and ibotenic acid. ''A ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Tardive Dyskinesia
Tardive dyskinesia (TD) is a disorder that results in involuntary repetitive body movements, which may include grimacing, sticking out the tongue or smacking the lips. Additionally, there may be rapid jerking movements or slow writhing movements. In about 20% of people with TD, the disorder interferes with daily functioning. Tardive dyskinesia occurs in some people as a result of long-term use of dopamine-receptor-blocking medications such as antipsychotics and metoclopramide. These medications are usually used for mental illness but may also be given for gastrointestinal or neurological problems. The condition typically develops only after months to years of use. The diagnosis is based on the symptoms after ruling out other potential causes. Efforts to prevent the condition include either using the lowest possible dose or discontinuing use of neuroleptics. Treatment includes stopping the neuroleptic medication if possible or switching to clozapine. Other medications such a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alkaloid
Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and, more rarely, other elements such as chlorine, bromine, and phosphorus.Chemical Encyclopedia: alkaloids xumuk.ru Alkaloids are produced by a large variety of organisms including , , Medicinal plant, plants, an ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Sedatives
A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity. This group is related to hypnotics. The term ''sedative'' describes drugs that serve to calm or relieve anxiety, whereas the term ''hypnotic'' describes drugs whose main purpose is to initiate, sustain, or lengthen sleep. Because these two functions frequently overlap, and because drugs in this class generally produce dose-dependent effects (ranging from anxiolysis to loss of consciousness) they are often referred to collectively as ''sedative-hypnotic'' drugs. Sedatives can be used to produce an overly-calming effect (alcohol being the most ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Glycine Receptor Antagonists
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 Henri ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
GABAA-rho Receptor Antagonists
The GABAA-rho receptor (previously known as the GABAC receptor) is a subclass of GABAA receptors composed entirely of rho (ρ) subunits. GABAA receptors including those of the ρ-subclass are ligand-gated ion channels responsible for mediating the effects of gamma-amino butyric acid ( GABA), the major inhibitory neurotransmitter in the brain. The GABAA-ρ receptor, like other GABAA receptors, is expressed in many areas of the brain, but in contrast to other GABAA receptors, the GABAA-ρ receptor has especially high expression in the retina. Nomenclature A second type of ionotropic GABA receptor, insensitive to typical allosteric modulators of GABAA receptor channels such as benzodiazepines and barbiturates, was designated GABAС receptor. Native responses of the GABAC receptor type occur in retinal bipolar or horizontal cells across vertebrate species. GABAС receptors are exclusively composed of ρ (rho) subunits that are related to GABAA receptor subunits. Although the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ibotenic Acid
Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compound and psychoactive drug which occurs naturally in ''Amanita muscaria'' and related species of mushrooms typically found in the temperate and boreal regions of the northern hemisphere. It is a prodrug of muscimol, broken down by the liver to that much stabler compound. It is a conformationally-restricted analogue of the neurotransmitter glutamate, and due to its structural similarity to this neurotransmitter, acts as a non-selective glutamate receptor agonist. Because of this, ibotenic acid can be a powerful neurotoxin in high doses, and is employed as a "brain-lesioning agent" through cranial injections in scientific research. The neurotoxic effects appear to be dose-related and risks are unclear through consumption of ibotenic-acid containing fungi, although thought to be negligible in small doses. Pharmacology Ibotenic acid acts as a potent agonist of t ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Ganaxolone
Ganaxolone, sold under the brand name Ztalmy, is a medication used to treat seizures in people with cyclin-dependent kinase-like 5 deficiency disorder, cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD). Ganaxolone was approved for medical use in the United States in March 2022. Pharmacology Mechanism of action The exact mechanism of action for ganaxolone is unknown; however, results from animal studies suggest that it acts by blocking seizure propagation and elevating seizure thresholds. Ganaxolone is thought to modulate both synapse, synaptic and extrasynaptic GABAA receptors to normalize over-excited neurons. Ganaxolone's activation of the extrasynaptic receptor is an additional mechanism that provides stabilizing effects that potentially differentiates it from other drugs that increase GABA signaling. Ganaxolone binds to allosteric sites of the GABAA receptor to modulate and open the Chloride channel, chloride ion channel, resulting in a Hyperpolarization ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CI-966
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. In a phase I human clinical trial while under development for the treatment of epilepsy, CI-966 was assessed at doses of 1–10 mg, 25 mg, and 50 mg. While the 1–10 mg dosages were well tolerated, the 25 mg dose produced memory deficits and the 50 mg dose was found to produce "a variety of severe neurological and psychiatric symptoms" and "serious psychotic adverse effects" of prolonged (several-day) duration and demonstrated "severe adverse ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Amanita Muscaria
''Amanita muscaria'', commonly known as the fly agaric or fly amanita, is a basidiomycete of the genus ''Amanita''. It is also a muscimol mushroom. Native throughout the temperate and boreal regions of the Northern Hemisphere, ''Amanita muscaria'' has been unintentionally introduced to many countries in the Southern Hemisphere, generally as a symbiont with pine and birch plantations, and is now a true cosmopolitan species. It associates with various deciduous and coniferous trees. Arguably the most iconic toadstool species, the fly agaric is a large white- gilled, white-spotted, usually red mushroom, and is one of the most recognizable and widely encountered in popular culture, including in video games—e.g., the extensive use of a recognizable ''Amanita muscaria'' in the Mario franchise and its Super Mushroom power-up—and television—e.g., the houses in The Smurfs franchise. Despite its easily distinguishable features, ''Amanita muscaria'' is a fungus with several know ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
