NMDA receptor antagonist
Encyclopedia
NMDA receptor antagonists are a class of anesthetics that work to antagonize
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...

, or inhibit the action of, the N-methyl d-aspartate
NMDA
N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...

 receptor (NMDAR
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....

). They are used as anesthesia
Anesthesia
Anesthesia, or anaesthesia , traditionally meant the condition of having sensation blocked or temporarily taken away...

 for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia
Dissociative drug
Dissociatives are a class of psychoactive drugs which are said to reduce or block signals to the conscious mind from other parts of the brain...

. There is evidence that NMDA receptor antagonists can cause a certain type of neurotoxicity
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

 or brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...

 referred to as Olney's Lesions
Olney's lesions
Olney's lesions, also known as NMDA receptor antagonist neurotoxicity , are a potential form of brain damage. They are named after John Olney, who conducted a study investigating neurotoxicity caused by PCP and related drugs in 1989.-History:...

 in rodent
Rodent
Rodentia is an order of mammals also known as rodents, characterised by two continuously growing incisors in the upper and lower jaws which must be kept short by gnawing....

s, though such damage has never been observed in primate
Primate
A primate is a mammal of the order Primates , which contains prosimians and simians. Primates arose from ancestors that lived in the trees of tropical forests; many primate characteristics represent adaptations to life in this challenging three-dimensional environment...

s like human
Human
Humans are the only living species in the Homo genus...

s.

Several synthetic opioids function additionally as NMDA-Antagonists, such as Meperidine, Methadone
Methadone
Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...

, Dextropropoxyphene
Dextropropoxyphene
Dextropropoxyphene, manufactured by Eli Lilly and Company, is an analgesic in the opioid category. It is intended to treat mild pain and has, in addition, anti-tussive and local anesthetic effects. It has been taken off the market in Europe and the US due to concerns of fatal overdoses and...

, Tramadol
Tramadol
Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...

 and Ketobemidone
Ketobemidone
Ketobemidone is a powerful opioid analgesic. Its effectiveness against pain is in the same range as morphine, and it also has some NMDA-antagonist properties imparted by it's metabolite norketobemidone. This makes it useful for some types of pain that don't respond well to other opioids...

.

Some NMDA receptor antagonists, including but not limited to ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

 (K), dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

 (DXM), phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...

 (PCP), and nitrous oxide
Nitrous oxide
Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...

 (N2O) are popular as recreational drugs for their dissociative, hallucinogenic, and/or euphoriant
Euphoriant
A euphoriant is a type of psychoactive drug which tends to induce feelings of euphoria, the effects of which may include relaxation, anxiolysis, stress relief, mood lift, pleasure, and a rush although these effects are not necessary for a drug to be a euphoriant. Many euphoriants are notorious for...

 properties. When used recreationally, they are classified as dissociative drug
Dissociative drug
Dissociatives are a class of psychoactive drugs which are said to reduce or block signals to the conscious mind from other parts of the brain...

s.

Uses and effects

NMDA receptor antagonists induce a state called dissociative anesthesia
Dissociative drug
Dissociatives are a class of psychoactive drugs which are said to reduce or block signals to the conscious mind from other parts of the brain...

, marked by catalepsy
Catalepsy
Catalepsy is also a term used by hypnotists to refer to the state of making a hypnotised subject's arm, leg or back rigid. "Arm catalepsy" is often a pre-hypnotic test performed prior to an induction into a full trance.-Causes:...

, amnesia
Amnesia
Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...

, and analgesia. Ketamine is a favored anesthetic for emergency patients with unknown medical history and in the treatment of burn victims because it depresses breathing and circulation less than other anesthetics. The NMDA receptor antagonist dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

 is one of the most commonly used cough suppressants in the world.

Depressed NMDA receptor function is associated with an array of negative symptoms. For example, NMDA receptor hypofunction that occurs as the brain ages may be partially responsible for memory deficits
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....

 associated with aging. Schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...

 may also have to do with irregular NMDA receptor function (the glutamate hypothesis of schizophrenia
Glutamate hypothesis of schizophrenia
The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors...

).Increased levels of another NMDA antagonist, kynurenic acid
Kynurenic acid
Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors...

, may aggravate the symptoms of schizophrenia, according to the "kynurenic hypothesis".NMDA receptor antagonists can mimic these problems; they sometimes induce "psychotomimetic
Psychotomimetic
A drug with psychotomimetic actions mimics the symptoms of psychosis, including delusions and/or delirium, as opposed to just hallucinations. Some drugs of the opioid class have psychotomimetic effects, such as pentazocine and butorphanol....

" side effects, symptoms resembling psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...

.Such side effects caused by NMDA receptor inhibitors include hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...

s, paranoid delusions, confusion
ConFusion
ConFusion is an annual science fiction convention organized by the Stilyagi Air Corps and its parent organization, the Ann Arbor Science Fiction Association. Commonly, it is held the third weekend of January. It is the oldest science fiction convention in Michigan, a regional, general SF con...

, difficulty concentrating
Attention
Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....

, agitation
Psychomotor agitation
Psychomotor agitation is a series of unintentional and purposeless motions that stem from mental tension and anxiety of an individual. This includes pacing around a room, wringing one's hands, pulling off clothing and putting it back on and other similar actions...

, alterations in mood
Mood (psychology)
A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....

, nightmare
Nightmare
A nightmare is an unpleasant dream that can cause a strong negative emotional response from the mind, typically fear or horror, but also despair, anxiety and great sadness. The dream may contain situations of danger, discomfort, psychological or physical terror...

s, catatonia
Catatonia
Catatonia is a state of neurogenic motor immobility, and behavioral abnormality manifested by stupor. It was first described in 1874: Die Katatonie oder das Spannungsirresein ....

, ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

, anaesthesia, and learning
Learning
Learning is acquiring new or modifying existing knowledge, behaviors, skills, values, or preferences and may involve synthesizing different types of information. The ability to learn is possessed by humans, animals and some machines. Progress over time tends to follow learning curves.Human learning...

 and memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....

 deficits.

Because of these psychotomimetic effects, NMDA receptor antagonists, especially phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...

, ketamine
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

, and dextromethorphan
Dextromethorphan
Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

, are used as recreational drugs. At subanesthetic doses, these drugs have mild stimulant effects, and at higher doses, begin inducing dissociation and hallucinations.

Most NMDA receptor antagonists are metabolized in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

. Frequent administration of most NMDA receptor antagonists can lead to tolerance, whereby the liver will more quickly eliminate NMDA receptor antagonists from the bloodstream.

Neurotoxicity

Exposure to NMDA receptor antagonists may cause serious brain damage in the cingulate cortex
Cingulate cortex
The cingulate cortex is a part of the brain situated in the medial aspect of the cortex. It includes the cortex of the cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cingulate sulcus...

 and retrosplenial cortex regions of the brain,
but evidence towards this hypothesis is not very strong at the moment. The experimental NMDA receptor antagonist MK-801 has been shown to cause neural vacuolization
Vacuolization
Vacuolization is the formation of vacuoles within or adjacent to cells, and, in dermatopathology, often refers to the basal cell-basement membrane zone area....

 in test rodents that later develop into irreversible lesions called "Olney's Lesions." Many drugs have been found that lessen the risk of neurotoxicity from NMDA receptor antagonists. Centrally acting alpha 2
Alpha-2 adrenergic receptor
The alpha-2 adrenergic receptor is a G protein-coupled receptor associated with the Gi heterotrimeric G-protein. It consists of three highly homologous subtypes, including α2A-, α2B-, and α2C-adrenergic. Some species other than humans express a fourth α2D-adrenergic receptor as well...

 agonist
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...

s such as clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...

 and guanfacine
Guanfacine
Guanfacine is a sympatholytic. It is an agonist of the α2A subtype of norepinephrine receptors. These receptors are concentrated heavily in the prefrontal cortex and the locus coeruleus, with the potential to improve attention abilities via modulating post-synaptic α2A receptors in the prefrontal...

 are thought to most specifically target the etiology
Etiology
Etiology is the study of causation, or origination. The word is derived from the Greek , aitiologia, "giving a reason for" ....

 of NMDA neurotoxicity. Other drugs acting on various neurotransmitter systems known to inhibit NMDA antagonist neurotoxicity include: anticholinergics, diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...

, barbiturates, ethanol
Ethanol
Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

, 5-HT2A serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 agonists, and muscimol
Muscimol
Muscimol is the major psychoactive alkaloid present in many mushrooms of the Amanita genus. Unlike psilocin , which is a serotonergic psychedelic and agonist for the 5-HT2A receptor set, muscimol is a potent, selective agonist for the GABAA receptor set and is a deliriant as a opposed...

.

Potential for treatment of excitotoxicity

Since NMDA receptors are one of the most harmful factors in excitotoxicity
Excitotoxicity
Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate such as the NMDA receptor and AMPA receptor are...

, antagonists of the receptors have held much promise for the treatment of conditions that involve excitotoxicity, including traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...

, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

, and neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. This is counterbalanced by the risk of developing Olney's lesions
Olney's lesions
Olney's lesions, also known as NMDA receptor antagonist neurotoxicity , are a potential form of brain damage. They are named after John Olney, who conducted a study investigating neurotoxicity caused by PCP and related drugs in 1989.-History:...

, although there is evidence against Olney's lesions forming in humans, and studies have started to find agents that prevent this neurotoxicity. Most clinical trials involving NMDA receptor antagonists have failed due to unwanted side effects of the drugs; since the receptors also play an important role in normal glutamatergic function, blocking them has harmful effects. These results have not yet been reproduced in humans, however. William White once wrote a paper on the "potential" dangers of these lesions but later retracted his hypothesis as "depression-induced nonsense". This interference with normal function could be responsible for neuronal death that sometimes results from NMDA receptor antagonist use.

Mechanism of action

The NMDA receptor is an ionotropic receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, glutamate and glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...

 must bind to the NMDA receptor. An NMDA receptor that has glycine and glutamate bound to it and has an open ion channel is called "activated."

Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories: Competitive antagonist
Competitive antagonist
A competitive antagonist is a receptor antagonist that binds to a receptor but does not activate the receptor. The antagonist will compete with available agonist for receptor binding sites on the same receptor...

s, which bind to and block the binding site of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...

 glutamate; glycine antagonists, which bind to and block the glycine site; noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites; and uncompetitive antagonists, which block the ion channel by binding to a site within it.

Competitive antagonists

  • AP5 (APV, R-2-amino-5-phosphonopentanoate)
  • AP7 (2-amino-7-phosphonoheptanoic acid)
  • CPPene
    CPPene
    Midafotel is a potent, competitive antagonist at the NMDA receptor. It was originally designed as a potential therapy for excitotoxicity, epilepsy or neuropathic pain. It looked very promising in in vitro trials proving to be a potent competitive antagonist at the NMDA without affecting other...

     (3-[(R)-2-carboxypiperazin-4-yl]-prop-2-enyl-1-phosphonic acid)
  • Selfotel
    Selfotel
    Selfotel is a drug which acts as a competitive NMDA antagonist, directly competing with glutamate for binding to the receptor...

    : an axiolytic, anticonvulsant but with possible neurotoxic effects.

Uncompetitive channel blockers

  • Amantadine
    Amantadine
    Amantadine is the organic compound known formally as 1-adamantylamine or 1-aminoadamantane. The molecule consists of adamantane backbone that has an amino group substituted at one of the four methyne positions. This pharmaceutical is sold under the name Symmetrel for use both as an antiviral and an...

    : used for treating Parkinson's disease
    Parkinson's disease
    Parkinson's disease is a degenerative disorder of the central nervous system...

     and influenza
    Influenza
    Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...

     and Alzheimer's.
  • Dextrallorphan
    Dextrallorphan
    Dextrallorphan is a drug of the morphinan class known in scientific research. It acts as a σ1 receptor agonist, κ-opioid receptor agonist, and NMDA receptor antagonist. It has no significant affinity for the σ2, μ-opioid, or δ-opioid receptor, or for the serotonin or norepinephrine transporter...

    : a more potent analogue of dextromethorphan.
  • Dextromethorphan
    Dextromethorphan
    Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

    : a common antitussive found in cough medicines.
  • Dextrorphan
    Dextrorphan
    Dextrorphan is a psychoactive drug of the morphinan chemical class which acts as an antitussive or cough suppressant and dissociative hallucinogen. It is the dextro-stereoisomer of racemorphan, the levo-half being levorphanol. Dextrorphan is produced by O-demethylation of dextromethorphan by CYP2D6...

    : active metabolite of dextromethorphan.
  • Dizocilpine
    Dizocilpine
    Dizocilpine , also known as MK-801, is a non-competitive antagonist of the N-methyl-d-aspartate receptor, a glutamate receptor. Glutamate is the brain's primary excitatory neurotransmitter...

     (MK-801): an experimental drug used in scientific research.
  • Ethanol
    Ethanol
    Ethanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...

    : also known as alcohol
    Alcoholic beverage
    An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...

    , a widely used legal intoxicant.
  • Eticyclidine
    Eticyclidine
    Eticyclidine is a dissociative anesthetic drug with hallucinogenic effects. It is similar in effects to phencyclidine but is slightly more potent...

    : a Schedule I
    Controlled Substances Act
    The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

     controlled substance in the United States.
  • Gacyclidine
    Gacyclidine
    Gacyclidine is a psychoactive drug which acts as a dissociative via functioning as a non-competitive NMDA receptor antagonist. It is closely related to phencyclidine , and specifically, is a derivative of tenocyclidine .-Synthesis:...

    : an experimental drug developed for neuroprotection.
  • Ibogaine
    Ibogaine
    Ibogaine is a naturally occurring psychoactive substance found in a number of plants, principally in a member of the Apocynaceae family known as Iboga . A hallucinogen with both psychedelic and dissociative properties, the substance is banned in some countries; in other countries it is being used...

    : a Schedule I
    Controlled Substances Act
    The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

     controlled substance in the United States.
  • Magnesium
    Magnesium
    Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

  • Memantine: treatment for Alzheimer's disease.
  • Methoxetamine
    Methoxetamine
    Methoxetamine or 3-MeO-2-Oxo-PCE is a chemical of the arylcyclohexylamine class which has been sold as a designer drug. It is a derivative of ketamine that also contains structural features of eticyclidine and 3-MeO-PCP...

    : a novel designer drug sold on the internet.
  • Nitrous oxide
    Nitrous oxide
    Nitrous oxide, commonly known as laughing gas or sweet air, is a chemical compound with the formula . It is an oxide of nitrogen. At room temperature, it is a colorless non-flammable gas, with a slightly sweet odor and taste. It is used in surgery and dentistry for its anesthetic and analgesic...

    : used for anesthesia, particularly in dentistry.
  • Phencyclidine
    Phencyclidine
    Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...

    : a Schedule II
    Controlled Substances Act
    The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

     controlled substance in the United States.
  • Rolicyclidine
    Rolicyclidine
    Rolicyclidine is a dissociative anesthetic drug with hallucinogenic and sedative effects. It is similar in effects to phencyclidine but is slightly less potent and has less stimulant effects instead producing a sedative effect described as being somewhat similar to a barbiturate, but with...

    : a Schedule I
    Controlled Substances Act
    The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

     controlled substance in the United States.
  • Tenocyclidine
    Tenocyclidine
    Tenocyclidine is a dissociative anesthetic drug with stimulant and hallucinogenic effects. It is similar in effects to phencyclidine but is considerably more potent. TCP has slightly different binding properties to PCP, with more affinity for the NMDA receptors, but less affinity for the sigma...

    : a Schedule I
    Controlled Substances Act
    The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...

     controlled substance in the United States.
  • Methoxydine: 4-meo-pcp
  • Tiletamine
    Tiletamine
    Tiletamine is a dissociative anesthetic and pharmacologically classified as an NMDA receptor antagonist. It is related chemically and pharmacologically to other anesthetics in this family such as ketamine and phencyclidine...

    : an animal anesthetic.
  • Xenon
    Xenon
    Xenon is a chemical element with the symbol Xe and atomic number 54. The element name is pronounced or . A colorless, heavy, odorless noble gas, xenon occurs in the Earth's atmosphere in trace amounts...

    : an anesthetic.
  • Neramexane
    Neramexane
    Neramexane is a drug related to memantine, which acts as an NMDA antagonist and has neuroprotective effects. It is being developed for various possible applications, including treatment of tinnitus, Alzheimer's disease, drug addiction and as an analgesic...

    : a memantine analogue with nootropic, antidepressant properties. Also a nicotinic acetylcholine antagonist.
  • Eliprodil
    Eliprodil
    Eliprodil is a drug which acts as an NMDA antagonist, binding to the polyamine modulatory site. It has neuroprotective and anticonvulsant effects in animal studies, but does not support self administration or substitute for phencyclidine, and does not produce sedation or amnesia...

    : an anticonvulsant with neuroprotective drug.
  • Etoxadrol
    Etoxadrol
    Etoxadrol is a dissociative anaesthetic drug which has been found to be an NMDA antagonist and produces similar effects to PCP in animals. Etoxadrol, along with another related drug dexoxadrol, were developed as analgesics for use in humans, but development was discontinued after patients reported...

    : a potent dissociative similar to PCP.
  • Dexoxadrol
    Dexoxadrol
    Dexoxadrol is a dissociative anaesthetic drug which has been found to be an NMDA antagonist and produces similar effects to PCP in animals. Dexoxadrol, along with another related drug etoxadrol, were developed as analgesics for use in humans, but development was discontinued after patients...

    : similar to etoxadrol.
  • NEFA
    NEFA (drug)
    NEFA is a moderate affinity NMDA antagonist . It is a structural analog of phencyclidine.- References :...

    : a moderate affinity antagonist.
  • Remacemide
    Remacemide
    Remacemide is a drug which acts as a low-affinity NMDA antagonist with sodium channel blocking properties. It has been studied for the treatment of acute ischemic stroke and epilepsy....

    : a low affinity antagonist also a sodium-channel blocker.
  • Delucemine
    Delucemine
    Delucemine is a drug which acts as an NMDA antagonist and a serotonin reuptake inhibitor, and has neuroprotective effects. It was originally investigated for the treatment of stroke but is now being studied as a potential antidepressant. It is currently in clinical trials.S.T. Moe, D.L. Smith, K....

    : also a SSRI with neuroprotective properties.
  • 8A-PDHQ: a high affinity PCP structural analogue.

Non-competitive antagonists

  • Aptiganel
    Aptiganel
    Aptiganel is a drug which acts as a noncompetitive NMDA antagonist. It has neuroprotective effects and was researched for potential use in the treatment of stroke, but despite positive results in animal studies, human trials showed limited efficacy, as well as undesirable side effects such as...

     (Cerestat, CNS-1102): binds the Mg2+
    Magnesium
    Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...

     binding site within the channel of the NMDA receptor.
  • HU-211: an enantiomer of the potent cannabinoid HU-210
    HU-210
    HU-210 is a synthetic cannabinoid that was first synthesized in 1988 from -Myrtenol by the group led by Professor Raphael Mechoulam at the Hebrew University. HU-210 is 100 to 800 times more potent than natural THC from cannabis and has an extended duration of action...

     which lacks cannabinoid effects and instead acts as a potent non-competitive NMDA antagonist.
  • Remacemide
    Remacemide
    Remacemide is a drug which acts as a low-affinity NMDA antagonist with sodium channel blocking properties. It has been studied for the treatment of acute ischemic stroke and epilepsy....

    : principle metabolite
    Metabolite
    Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

     is an uncompetitive antagonist with a low affinity for the binding site.
  • Rhynchophylline
    Rhynchophylline
    Rhynchophylline is an alkaloid found in certain Uncaria species, notably Uncaria rhynchophylla and Uncaria tomentosa. It is a non-competitive NMDA antagonist and calcium channel blocker...

     an alkaloid.
  • Ketamine
    Ketamine
    Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...

    : an animal and human anesthetic and recreational drug.

Glycine antagonists

These drugs act at the glycine binding site:
  • 1-Aminocyclopropanecarboxylic acid (ACPC)
  • 7-Chlorokynurenate
  • DCKA
    DCKA
    DCKA is a selective NMDA receptor antagonist acting at the glycine site on the NMDAR complex....

     (5,7-dichlorokynurenic acid)
  • Kynurenic acid
    Kynurenic acid
    Kynurenic acid is a product of the normal metabolism of amino acid L-tryptophan. It has been shown that kynurenic acid possesses neuroactive activity. It acts as an antiexcitotoxic and anticonvulsant, most likely through acting as an antagonist at excitatory amino acid receptors...

    : a naturally occurring antagonist
  • Lacosamide
    Lacosamide
    Lacosamide is a medication developed by UCB for the adjunctive treatment of partial-onset seizures and diabetic neuropathic pain marketed under the trade name Vimpat....

    : an investigational drug for the treatment of epilepsy
    Epilepsy
    Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...

     and diabetic neuropathic pain
    Diabetic neuropathy
    Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...

    .

See also

  • Neurotransmitters
  • Psychedelics
  • Long-term potentiation
    Long-term potentiation
    In neuroscience, long-term potentiation is a long-lasting enhancement in signal transmission between two neurons that results from stimulating them synchronously. It is one of several phenomena underlying synaptic plasticity, the ability of chemical synapses to change their strength...

  • NMDA
    NMDA
    N-Methyl-D-aspartic acid or N-Methyl-D-aspartate is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter which normally acts at that receptor...

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
x
OK