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| IUPAC name 3-amino-2-(4-chlorophenyl)-2-hydroxypropane-1-sulfonic acid | |
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3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
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PubChem CID | |
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CompTox Dashboard (EPA) | |
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| Properties | |
| C9H12ClNO4S | |
| Molar mass | 265.71 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
2-Hydroxysaclofen is a GABAB receptor antagonist and an analogue of saclofen.
2-Hydroxysaclofen binds to the GABAB receptor, but this is selective for the (S)-enantiomer, while the (R)-enantiomer does not bind to the GABAB protein. [1]
2-Hydroxysaclofen has been reported to be more potent than saclofen. [2]
A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: metabotropic and ionotropic receptors. While ionotropic receptors form an ion channel pore, metabotropic receptors are indirectly linked with ion channels through signal transduction mechanisms, such as G proteins.
Epibatidine is a chlorinated alkaloid that is secreted by the Ecuadoran frog Epipedobates anthonyi and poison dart frogs from the Ameerega genus. It was discovered by John W. Daly in 1974, but its structure was not fully elucidated until 1992. Whether epibatidine is the first observed example of a chlorinated alkaloid remains controversial, due to challenges in conclusively identifying the compound from the limited samples collected by Daly. By the time that high-resolution spectrometry was used in 1991, there remained less than one milligram of extract from Daly's samples, raising concerns about possible contamination. Samples from other batches of the same species of frog failed to yield epibatidine.
GABAB receptors (GABABR) are G-protein coupled receptors for gamma-aminobutyric acid (GABA), therefore making them metabotropic receptors, that are linked via G-proteins to potassium channels. The changing potassium concentrations hyperpolarize the cell at the end of an action potential. The reversal potential of the GABAB-mediated IPSP is –100 mV, which is much more hyperpolarized than the GABAA IPSP. GABAB receptors are found in the central nervous system and the autonomic division of the peripheral nervous system.
Phenibut, sold under the brand names Anvifen, Fenibut, and Noofen among others, is a central nervous system depressant with anxiolytic effects, and is used to treat anxiety, insomnia, and for a variety of other indications. It is usually taken by mouth as a tablet, but may be given intravenously.
Saclofen 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. The action of saclofen on the central nervous system is understandably modest, because G-proteins rely on an enzyme cascade to alter cell behavior while ionotropic receptors immediately change the ionic permeability of the neuronal plasma membrane, thus changing its firing patterns. These particular receptors, presynaptically inhibit N- and P/Q- voltage-gated calcium channels (VGCCs) via a direct interaction of the dissociated beta gamma subunit of the g-protein with the intracellular loop between the 1st and 2nd domain of the VGCC's alpha-subunit; postsynaptically, these potentiate Kir currents. Both result in inhibitory effects.
GABA gamma-aminobutyric acid (GABA) is a key chemical messenger or a neurotransmitter in the central nervous system, that significantly inhibits neuronal transmission. GABA calms the brain and controls several physiological processes, such as stress, anxiety, and sleep. GABAA receptors are a class of ionotropic receptors that are triggered by GABA. They are made up of five subunits that are assembled in various configurations to create distinct receptor subtypes. The direct influx of chloride ions causes rapid inhibitory responses. GABAB receptors are another type of metabotropic receptor that modifies intracellular signaling pathways to provide slower, sustained inhibitory responses. At synapses, GABAA receptors facilitate rapid inhibitory neurotransmission, whereas GABAB receptor which comprise GABA B1 and GABA B2 subunits—control neurotransmitter release and cellular excitability over a longer period of time. These unique qualities help explain the various ways that GABAergic neurotransmission controls brain communication and neuronal function.
Homotaurine is a natural sulfonic acid found in seaweed. It is analogous to taurine, but with an extra carbon in its chain. It has GABAergic activity, apparently by mimicking GABA, which it resembles.
The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is an excitatory G protein-coupled receptor (GPCR) that binds the neurotransmitter and psychoactive drug γ-hydroxybutyric acid (GHB). As solute carrier family 52 member 2 (SLC52A2), it is also a transporter for riboflavin.
Kavain is the main kavalactone found mostly in the roots of the kava plant.
Phaclofen, or phosphonobaclofen, is a selective antagonist for the GABAB receptor. It was the first selective GABAB antagonist discovered, but its utility was limited by the fact that it does not cross the blood brain barrier.
Alazocine, also known more commonly as N-allylnormetazocine (NANM), is a synthetic opioid analgesic of the benzomorphan family related to metazocine, which was never marketed. In addition to its opioid activity, the drug is a sigma receptor agonist, and has been used widely in scientific research in studies of this receptor. Alazocine is described as a potent analgesic, psychotomimetic or hallucinogen, and opioid antagonist. Moreover, one of its enantiomers was the first compound that was found to selectively label the σ1 receptor, and led to the discovery and characterization of the receptor.
CGP-7930 was the first positive allosteric modulator of GABAB receptors described in literature. CGP7930 is also a GABAA receptor positive allosteric modulator and a blocker of Potassium channels.
SKF-97,541 is a compound used in scientific research which acts primarily as a selective GABAB receptor agonist. It has sedative effects in animal studies and is widely used in research into potential treatment of various types of drug addiction.
CGP-35348 is a compound used in scientific research which acts as an antagonist at GABAB receptors.
Quisqualamine is the α-decarboxylated analogue of quisqualic acid, as well as a relative of the neurotransmitters glutamate and γ-aminobutyric acid (GABA). α-Decarboxylation of excitatory amino acids can produce derivatives with inhibitory effects. Indeed, unlike quisqualic acid, quisqualamine has central depressant and neuroprotective properties and appears to act predominantly as an agonist of the GABAA receptor and also to a lesser extent as an agonist of the glycine receptor, due to the facts that its actions are inhibited in vitro by GABAA antagonists like bicuculline and picrotoxin and by the glycine antagonist strychnine, respectively. Mg2+ and DL-AP5, NMDA receptor blockers, CNQX, an antagonist of both the AMPA and kainate receptors, and 2-hydroxysaclofen, a GABAB receptor antagonist, do not affect quisqualamine's actions in vitro, suggesting that it does not directly affect the ionotropic glutamate receptors or the GABAB receptor in any way. Whether it binds to and acts upon any of the metabotropic glutamate receptors like its analogue quisqualic acid however is unclear.
HA-966 or (±)-3-amino-1-hydroxy-pyrrolidin-2-one is a molecule used in scientific research as a glycine receptor and NMDA receptor antagonist / low efficacy partial agonist. It has neuroprotective and anticonvulsant, anxiolytic, antinociceptive and sedative / hypnotic effects in animal models. Pilot human clinical trials in the early 1960s showed that HA-966 appeared to benefit patients with tremors of extrapyramidal origin.
Esmethadone (INNTooltip International Nonproprietary Name; developmental code name REL-1017), also known as dextromethadone, is the (S)-enantiomer of methadone. It acts as an N-methyl-D-aspartate receptor (NMDAR) antagonist, among other actions. Unlike levomethadone, it has low affinity for opioid receptors and lacks significant respiratory depressant action and abuse liability. Esmethadone is under development for the treatment of major depressive disorder. As of August 2022, it is in phase 3 clinical trials for this indication.
Norketamine, or N-desmethylketamine, is the major active metabolite of ketamine, which is formed mainly by CYP3A4. Similarly to ketamine, norketamine acts as a noncompetitive NMDA receptor antagonist, but is about 3–5 times less potent as an anesthetic in comparison.
A GABA analogue is a compound which is an analogue or derivative of the neurotransmitter gamma-Aminobutyric acid (GABA).
3-Aminopropylphosphinic acid, also known in the literature as 3-APPA or CGP 27492, is a compound used in scientific research which acts as an agonist at the GABAB receptor. It is part of a class of phosphinic acid GABAB agonists, which also includes SKF-97,541. It has a binding affinity (pKi) to the GABAB receptor of 8.30.
