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S-18986
S-18986 is a positive allosteric modulator of the AMPA receptor related to cyclothiazide. It has nootropic and neuroprotective effects in animal studies, and induces both production of BDNF and AMPA-mediated release of noradrenaline and acetylcholine in the hippocampus and frontal cortex of the brain. See also * AMPA receptor positive allosteric modulator AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system. Medical ... References AMPA receptor positive allosteric modulators Benzothiadiazines Experimental drugs {{nervous-system-drug-stub ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AMPA Receptor Positive Allosteric Modulators
AMPA receptor positive allosteric modulators are positive allosteric modulators (PAMs) of the receptor (AMPR), a type of ionotropic glutamate receptor which mediates most fast synaptic neurotransmission in the central nervous system. Medical applications AMPAR PAMs have cognition- and memory-enhancing and antidepressant-like effects in preclinical models, and have potential medical applications in the treatment of cognitive impairment (e.g., cognitive symptoms in schizophrenia, mild cognitive impairment), dementia (e.g., Alzheimer's disease), depression, and for other indications. They can broadly be divided into low-impact and high-impact potentiators, with high-impact potentiators able to produce comparatively more robust increases in AMPAR activation. However, high-impact AMPAR PAMs can cause motor coordination disruptions, convulsions, and neurotoxicity at sufficiently high doses, similarly to orthosteric AMPAR activators (i.e., active/glutamate site agonists). The ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Positive Allosteric Modulator
In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds to (i.e., an ''allosteric site'') is not the same one to which an endogenous agonist of the receptor would bind (i.e., an ''orthosteric site''). Modulators and agonists can both be called receptor ligands. Allosteric modulators can be 1 of 3 types either: positive, negative or neutral. Positive types increase the response of the receptor by increasing the probability that an agonist will bind to a receptor (i.e. affinity), increasing its ability to activate the receptor (i.e. efficacy), or both. Negative types decrease the agonist affinity and/or efficacy. Neutral types don't affect agonist activity but can stop other modulators from binding to an allosteric site. Some modulators also work as allosteric agonists. The term "allosteric" de ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AMPA Receptor
The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, or quisqualate receptor) is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the central nervous system (CNS). It has been traditionally classified as a non- NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. The receptor was first named the "quisqualate receptor" by Watkins and colleagues after a naturally occurring agonist quisqualate and was only later given the label "AMPA receptor" after the selective agonist developed by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The ''GRIA2''-encoded AMPA receptor ligand binding core (GluA2 LBD) was the first glutamate receptor ion channel domain to be crystallized. Structure and function Subunit composition AMPARs are composed of four types of ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Cyclothiazide
Cyclothiazide (Anhydron, Acquirel, Doburil, Fluidil, Renazide, Tensodiural, Valmiran), sometimes abbreviated CTZ, is a benzothiadiazide (thiazide) diuretic and antihypertensive that was originally introduced in the United States in 1963 by Eli Lilly and was subsequently also marketed in Europe and Japan. Related drugs include diazoxide, hydrochlorothiazide, and chlorothiazide. In 1993, it was discovered that cyclothiazide is a positive allosteric modulator of the AMPA and kainate receptors, capable of reducing or essentially eliminating rapid desensitization of the former receptor, and potentiating AMPA-mediated glutamate currents by as much as 18-fold at the highest concentration tested (100 μM). Additionally, in 2003, cyclothiazide was also found to act as a GABAA receptor negative allosteric modulator, potently inhibiting GABAA-mediated currents. In animals it is a powerful convulsant, robustly enhancing epileptiform activity and inducing seizures, but without producing a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nootropic
Nootropics ( , or ) ( colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote relaxation, particularly boosting mood, executive functions, attention, memory, creativity, or motivation in healthy individuals. The use of cognition-enhancing supplements by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for non-medical uses. Nonetheless, the international sales of cognitive- or mood-enhancing supplements have continued to grow over time and in 2012 reached 0.69 billion. With sales supported by global health trends, the market is expected to reach US$33.85 billion by the year 2030, at a CAGR of 14.8%. While most nootropics are not regulated, there a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Neuroprotective
Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal loss over time, which can be expressed as a differential equation. It is a widely explored treatment option for many central nervous system (CNS) disorders including neurodegenerative diseases, stroke, traumatic brain injury, spinal cord injury, and acute management of neurotoxin consumption (i.e. methamphetamine overdoses). Neuroprotection aims to prevent or slow disease progression and secondary injuries by halting or at least slowing the loss of neurons. Despite differences in symptoms or injuries associated with CNS disorders, many of the mechanisms behind neurodegeneration are the same. Common mechanisms of neuronal injury include decreased delivery of oxygen and glucose to the brain, energy failure, increased levels in oxidative st ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BDNF
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein found in the and the periphery. that, 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), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen. BDNF activates the TrkB tyrosine kinase receptor. Function BDNF acts on certain neurons of the central nervous system and the peripheral nervous system expressing TrkB, helping to support survival of existing neurons, and encouraging growth and differentiation of new neurons and synapses. In the brain it is active in the hippocampus, cortex, and basal forebrain—areas vital to learning, memory, and higher thinking. BDNF is also expressed in the retina, kidneys, prostate, motor neurons, and skeleta ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
AMPA
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ion channels in the central nervous system including AMPA, kainic acid and ''N''-methyl-D-aspartic acid (NMDA) channels. In the synapse, these receptors serve very different purposes. AMPA can be used experimentally to distinguish the activity of one receptor from the other in order to understand their differing functions. AMPA generates fast Fast or FAST may refer to: * Fast (noun), high speed or velocity * Fast (noun, verb), to practice fasting, abstaining from food and/or water for a certain period of time Acronyms and coded Computing and software * ''Faceted Application of Subje ... excitatory postsynaptic potentials (EPSP). AMPA activates AMPA receptors that are non-selective cationic channels allowing the passage of Na+ and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Noradrenaline
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', "near", and ''ren'', "kidney") is more commonly used in the United Kingdom, whereas "norepinephrine" (from Ancient Greek ἐπῐ́ (''epí''), "upon", and νεφρός (''nephrós''), "kidney") is usually preferred in the United States. "Norepinephrine" is also the international nonproprietary name given to the drug. Regardless of which name is used for the substance itself, parts of the body that produce or are affected by it are referred to as noradrenergic. The general function of norepinephrine is to mobilize the brain and body for action. Norepinephrine release is lowest during sleep, rises during wakefulness, and reaches much higher levels during situations of stress or danger, in the so-called fight-or-flight response. In the ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Acetylcholine
Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic. Substances that increase or decrease the overall activity of the cholinergic system are called cholinergics and anticholinergics, respectively. Acetylcholine is the neurotransmitter used at the neuromuscular junction—in other words, it is the chemical that motor neurons of the nervous system release in order to activate muscles. This property means that drugs that affect cholinergic systems can have very dangerous effects ranging from paralysis to convulsions. Acetylcholine is also a neurotransmitter in the autonomic nervous system, both as an internal transmitter for the sympathetic nervous system and as the final product released by the para ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Hippocampus
The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located in the allocortex, with neural projections into the neocortex in humans, as well as primates. The hippocampus, as the medial pallium, is a structure found in all vertebrates. In humans, it contains two main interlocking parts: the hippocampus proper (also called ''Ammon's horn''), and the dentate gyrus. In Alzheimer's disease (and other forms of dementia), the hippocampus is one of the first regions of the brain to suffer damage; short-term memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
