Dizocilpine
Encyclopedia
Dizocilpine also known as MK-801, is a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor
, a glutamate receptor. Glutamate is the brain's primary excitatory neurotransmitter
. The channel is normally blocked with a magnesium ion and requires depolarization
of the neuron
to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. MK-801 binds inside the ion channel
of the receptor
at the PCP
binding site and thus prevents the flow of ion
s, including an influx of calcium
(Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and likely has dissociative anesthetic properties, but it is not used clinically for this purpose due to the discovery of brain lesions, called Olney's lesions
(see below), in test rats. MK-801 is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It also inhibited the induction of long term potentiation. Instead, the NMDA receptor pore-blocker ketamine
is used as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary psychosis
in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used non-competitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
Dizocilpine has also been found to act as a nicotinic acetylcholine receptor
antagonist
. It has been shown to bind to and inhibit
the serotonin
and dopamine transporter
s as well.
.
(a process in which an excessive amount of extracellular glutamate overexcites glutamate receptor
s and harms neurons). Thus NMDA receptor antagonists including MK-801 have been extensively studied for use in treatment of diseases with excitotoxic components, such as stroke
, traumatic brain injury
, and neurodegenerative diseases such as Huntington's
, Alzheimer's
, and amyotrophic lateral sclerosis
. MK-801 has shown effectiveness in protecting neurons in cell culture
and animal models of excitotoxic neurodegeneration. The administration of MK-801 protected the hippocampus from ischemia-induced neurodegeneration in the gerbil. The ED50 (effective dose 50) for neuroprotection was 0.3 mg/kg and the majority of the animals were protected against the ischemia-induced damage at doses greater than or equal to 3 mg/kg, when MK-801 was given one hour prior to the occlusion of the carotid arteries, although other studies have shown protection up to 24 hours post-insult. Excitatory amino acids, such as glutamate and aspartate, are released in toxic amounts when the brain is deprived of blood and oxygen and NMDA receptors are thought to prevent the neurodegeneration through the inhibition of these receptors.
Behavioural studies have shown that NMDA receptors are involved in the development of psychological dependence caused by chronic administration of morphine. MK-801 suppressed the morphine-induced rewarding effect. It is suggested that stimulating NR2B subunits of the NMDA receptor and its associated kinases in the nucleus accumbens leads to the rewarding effect caused by morphine. Inhibition of this receptor and its kinases in the nucleus accumbens by co-treatment with NMDA antagonists prevents morphine-associated psychological dependence. An earlier study has show that the prevention of morphine-associated psychological dependence was not due to state-dependency effects induced by MK-801 but rather reflect the impairment of learning that is caused by NMDA antagonists. This is consistent with studies showing that MK-801 potentiates the addictive potential of morphine and other drugs (see below).
As an antidepressant, positive results were found in animal models of depression. NMDA antagonists like MK-801 have been shown in animal models to attenuate the hearing loss caused by aminoglycosides It is thought that aminoglycosides mimic endogenous polyamines at NMDA receptors and produce excitotoxic damage, leading to hair cell loss. Antagonizing NMDA receptors to reduce the excitotoxicity would prevent that hearing loss. MK-801 was found to block the development of kindled seizure
s, although it does not have any effect on completed kindled seizures. Oddly, it was discovered to decrease rabies
virus production and is believed to be the first neurotransmitter antagonist to present with antiviral activity. Rat cortical neuron cells were infected with the rabies virus and those incubated with MK-801 had virus produced reduced about 1000-fold. It is not known how MK-801 has this effect; the rabies virus suspension, without cells, was inoculated with MK-801 and the drug failed to produce a virucidal effect, indicated that the mechanism of action is something other than direct killing of the virus. It was also tested against herpes simplex, vesicular stomatitis, poliovirus type I, and human immunodeficiency virus. It did not have activity against these other viruses, however. MK-801 was also shown to potentiate the ability of levodopa
to ameliorate akinesia and muscular rigidity in a rodent model of parkinsonism
. When MK-801 was administered to rats 15 minutes after a spinal trauma, the long-term neurological recovery of the trauma was improved. However, NMDA antagonists like MK-801 have largely failed to show safety in clinical trial
s, possibly due to inhibition of NMDA receptor function that is necessary for normal neuron
al function. Since MK-801 is a particularly strong NMDA receptor antagonist, this drug is particularly likely to have psychotomimetic
side effects (such as hallucination
s) that result from NMDA receptor blockade. MK-801 had a promising future as a neuroprotective agent until neurotoxic-like effects, called Olney's Lesions
, were seen in certain brain
regions of test rats. Merck
, a drug company, promptly dropped development of MK-801.
/retrosplenial cortex. Other neurons in the area expressed an abnormal amount of heat shock protein
as well as increased glucose metabolism in response to NMDA antagonist exposure. Vacuoles began to form within 30 minutes of a subcutaneous dose of MK-801 1 mg/kg. Neurons in this area necrotized and were accompanied by a glial response involving astrocytes and microglia
.
However, it may be necessary to point out that Ketamine
was also found in animal models to produce Olney's Lesions, but not in humans.
and phencyclidine
(PCP), and causes far worse amnesia
and residual deficits in thinking, which have hindered its acceptance as a recreational drug.
Several animal studies have demonstrated the addictive potential of dizocilpine. Rats learned to lever-press in order to obtain injections of MK-801 into the nucleus accumbens and frontal cortex, however, when given a dopamine antagonist at the same time, the lever-pressing was not altered, which shows that the rewarding effect of MK-801 is not dependent on dopamine. Intraperitoneal administration of MK-801 also produced an enhancement in self-stimulation responding. Rhesus monkeys were trained to self-administer cocaine or phencyclidine, then were offered MK-801 instead. None of the four monkeys who were used to cocaine chose to self-administer MK-801 but three out of the four monkeys who had been using phencyclidine self-administered MK-801, suggesting again that MK-801 has potential as a recreational drug for those seeking a dissociative anaesthetic type of experience. It was found that MK-801 administration elicited conditioned place preference in animals, again demonstrating its reinforcing properties.
NMDA receptor antagonist
NMDA receptor antagonists are a class of anesthetics that work to antagonize, or inhibit the action of, the N-methyl d-aspartate receptor . They are used as anesthesia for animals and, less commonly, for humans; the state of anesthesia they induce is referred to as dissociative anesthesia...
, a glutamate receptor. Glutamate is the brain's primary excitatory 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...
. The channel is normally blocked with a magnesium ion and requires depolarization
Depolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
of the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
to remove the magnesium and allow the glutamate to open the channel, causing an influx of calcium, which then leads to subsequent depolarization. MK-801 binds inside the ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
of the receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
at the PCP
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
binding site and thus prevents the flow of ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s, including an influx of calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
(Ca2+), through the channel. Dizocilpine blocks NMDA receptors in a use- and voltage-dependent manner, since the channel must open for the drug to bind inside it. The drug acts as a potent anti-convulsant and likely has dissociative anesthetic properties, but it is not used clinically for this purpose due to the discovery of brain lesions, called 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:...
(see below), in test rats. MK-801 is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It also inhibited the induction of long term potentiation. Instead, the NMDA receptor pore-blocker 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...
is used as a dissociative anesthetic in human medical procedures. While ketamine may also trigger temporary 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"...
in certain individuals, its short half-life and lower potency make it a much safer clinical option. However, dizocilpine is the most frequently used non-competitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.
Dizocilpine has also been found to act as a nicotinic acetylcholine receptor
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
antagonist
Nicotinic antagonist
A nicotinic antagonist is a type of anticholinergic that inhibits the action at nicotinic acetylcholine receptors. These compounds are mainly used for peripheral muscle paralysis in surgery, but some centrally acting compounds such as bupropion, mecamylamine, and 18-methoxycoronaridine block...
. It has been shown to bind to and inhibit
Reuptake inhibitor
A reuptake inhibitor , also known as a transporter blocker, is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron, leading to an increase in the extracellular concentrations of the neurotransmitter and therefore an...
the serotonin
Serotonin transporter
The serotonin transporter is a monoamine transporter protein.This protein is an integral membrane protein that transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons. This transport of serotonin by the SERT protein terminates the action of serotonin and recycles it...
and dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
s as well.
An animal model of schizophrenia
MK-801 has a great deal of potential to be used in research in creating animal models of schizophrenia. Unlike dopaminergic agonists, which mimic only the positive symptoms of schizophrenia, a single injection of MK801 was successful in modelling both the positive and negative symptoms of schizophrenia. Another study found that although repeated low doses of MK-801 was only successful in mimicked such behavioural changes such as a slight hyperlocomotion and increased pre-pulse inhibition, repeated administration of a higher dose mimicked both the above changes as well as the neurochemical alterations found in first-episode schizophrenic patients. and not only has temporary use been shown to mimic psychosis but chronic administration in laboratory animals resulted in similar neuropathological changes as in schizophreniaSchizophrenia
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...
.
Possible future medical uses
The effects of MK-801 at NMDA receptors are clear and significant. NMDA receptors are key in the progression of excitotoxicityExcitotoxicity
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...
(a process in which an excessive amount of extracellular glutamate overexcites glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...
s and harms neurons). Thus NMDA receptor antagonists including MK-801 have been extensively studied for use in treatment of diseases with excitotoxic components, such as 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...
, 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...
, and neurodegenerative diseases such as Huntington's
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
, Alzheimer's
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
, and amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis , also referred to as Lou Gehrig's disease, is a form of motor neuron disease caused by the degeneration of upper and lower neurons, located in the ventral horn of the spinal cord and the cortical neurons that provide their efferent input...
. MK-801 has shown effectiveness in protecting neurons in cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
and animal models of excitotoxic neurodegeneration. The administration of MK-801 protected the hippocampus from ischemia-induced neurodegeneration in the gerbil. The ED50 (effective dose 50) for neuroprotection was 0.3 mg/kg and the majority of the animals were protected against the ischemia-induced damage at doses greater than or equal to 3 mg/kg, when MK-801 was given one hour prior to the occlusion of the carotid arteries, although other studies have shown protection up to 24 hours post-insult. Excitatory amino acids, such as glutamate and aspartate, are released in toxic amounts when the brain is deprived of blood and oxygen and NMDA receptors are thought to prevent the neurodegeneration through the inhibition of these receptors.
Behavioural studies have shown that NMDA receptors are involved in the development of psychological dependence caused by chronic administration of morphine. MK-801 suppressed the morphine-induced rewarding effect. It is suggested that stimulating NR2B subunits of the NMDA receptor and its associated kinases in the nucleus accumbens leads to the rewarding effect caused by morphine. Inhibition of this receptor and its kinases in the nucleus accumbens by co-treatment with NMDA antagonists prevents morphine-associated psychological dependence. An earlier study has show that the prevention of morphine-associated psychological dependence was not due to state-dependency effects induced by MK-801 but rather reflect the impairment of learning that is caused by NMDA antagonists. This is consistent with studies showing that MK-801 potentiates the addictive potential of morphine and other drugs (see below).
As an antidepressant, positive results were found in animal models of depression. NMDA antagonists like MK-801 have been shown in animal models to attenuate the hearing loss caused by aminoglycosides It is thought that aminoglycosides mimic endogenous polyamines at NMDA receptors and produce excitotoxic damage, leading to hair cell loss. Antagonizing NMDA receptors to reduce the excitotoxicity would prevent that hearing loss. MK-801 was found to block the development of kindled seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, although it does not have any effect on completed kindled seizures. Oddly, it was discovered to decrease rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
virus production and is believed to be the first neurotransmitter antagonist to present with antiviral activity. Rat cortical neuron cells were infected with the rabies virus and those incubated with MK-801 had virus produced reduced about 1000-fold. It is not known how MK-801 has this effect; the rabies virus suspension, without cells, was inoculated with MK-801 and the drug failed to produce a virucidal effect, indicated that the mechanism of action is something other than direct killing of the virus. It was also tested against herpes simplex, vesicular stomatitis, poliovirus type I, and human immunodeficiency virus. It did not have activity against these other viruses, however. MK-801 was also shown to potentiate the ability of levodopa
Levodopa
L-DOPA is a chemical that is made and used as part of the normal biology of some animals and plants. Some animals including humans make it via biosynthesis from the amino acid L-tyrosine. L-DOPA is the precursor to the neurotransmitters dopamine, norepinephrine , and epinephrine collectively...
to ameliorate akinesia and muscular rigidity in a rodent model of parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
. When MK-801 was administered to rats 15 minutes after a spinal trauma, the long-term neurological recovery of the trauma was improved. However, NMDA antagonists like MK-801 have largely failed to show safety in clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
s, possibly due to inhibition of NMDA receptor function that is necessary for normal neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
al function. Since MK-801 is a particularly strong NMDA receptor antagonist, this drug is particularly likely to have 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 (such as 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) that result from NMDA receptor blockade. MK-801 had a promising future as a neuroprotective agent until neurotoxic-like effects, called 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:...
, were seen in certain brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
regions of test rats. Merck
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...
, a drug company, promptly dropped development of MK-801.
Olney's lesions
MK-801, along with other NMDA antagonists, induce the formation of brain lesions first discovered by John W. Olney in 1989. MK-801 leads to the development of neuronal vacuolization in the posterior cingulatePosterior cingulate
The posterior cingulate cortex is the backmost part of the cingulate cortex, lying behind the anterior cingulate cortex.This is the upper part of the "limbic lobe". The cingulate cortex is made up of an area around the midline of the brain...
/retrosplenial cortex. Other neurons in the area expressed an abnormal amount of heat shock protein
Heat shock protein
Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...
as well as increased glucose metabolism in response to NMDA antagonist exposure. Vacuoles began to form within 30 minutes of a subcutaneous dose of MK-801 1 mg/kg. Neurons in this area necrotized and were accompanied by a glial response involving astrocytes and microglia
Microglia
Microglia are a type of glial cell that are the resident macrophages of the brain and spinal cord, and thus act as the first and main form of active immune defense in the central nervous system . Microglia constitute 20% of the total glial cell population within the brain...
.
However, it may be necessary to point out that 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...
was also found in animal models to produce Olney's Lesions, but not in humans.
Recreational use
Dizocilpine may be effective as a recreational drug, and may have an active dose in the 50-100 μg range. Little is known in this context about its effects, dosage, and risks. The high potency of dizocilpine makes its dosage more difficult to accurately control when compared to other similar drugs. As a result, the chances of overdosing are high. Users tend to report that the experience is not as enjoyable as other dissociative drugs, and it is often accompanied by strong auditory hallucinations. Also, dizocilpine is much longer-lasting than similar dissociative drugs such as ketamineKetamine
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 phencyclidine
Phencyclidine
Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
(PCP), and causes far worse 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 residual deficits in thinking, which have hindered its acceptance as a recreational drug.
Several animal studies have demonstrated the addictive potential of dizocilpine. Rats learned to lever-press in order to obtain injections of MK-801 into the nucleus accumbens and frontal cortex, however, when given a dopamine antagonist at the same time, the lever-pressing was not altered, which shows that the rewarding effect of MK-801 is not dependent on dopamine. Intraperitoneal administration of MK-801 also produced an enhancement in self-stimulation responding. Rhesus monkeys were trained to self-administer cocaine or phencyclidine, then were offered MK-801 instead. None of the four monkeys who were used to cocaine chose to self-administer MK-801 but three out of the four monkeys who had been using phencyclidine self-administered MK-801, suggesting again that MK-801 has potential as a recreational drug for those seeking a dissociative anaesthetic type of experience. It was found that MK-801 administration elicited conditioned place preference in animals, again demonstrating its reinforcing properties.
See also
- Dissociative
- Dextromethorphan (DXM)DextromethorphanDextromethorphan 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...
- KetamineKetamineKetamine 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...
- Phencyclidine (PCP)PhencyclidinePhencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...
- Dextromethorphan (DXM)
- Glutamate
- NMDA receptorNMDA receptorThe NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
- NMDA antagonists
- Olney's lesionsOlney's lesionsOlney'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:...
- PsychosisPsychosisPsychosis 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"...