Phencyclidine

Last updated
Phencyclidine
Phencyclidine.svg
Phencyclidine-from-xtal-3D-balls.png
Clinical data
Trade names Sernyl, Sernylan (both discontinued)
Other namesCI-395; Phenylcyclohexylpiperidine; "Angel dust" [1]
AHFS/Drugs.com phencyclidine
Dependence
liability 		Physical: Low [2] Psychological: Low–moderate [3]
Addiction
liability 		Variable, reported from low to high [4] [5] [6]
Routes of
administration 		Smoking, injection, snorted, by mouth [7] [8]
Drug class NMDA receptor antagonists; General anesthetics; Dissociative hallucinogens [7]
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Metabolism Oxidative hydroxylation in liver by CYP450 enzymes, glucuronidation
Metabolites PCHP, PPC, PCAA
Onset of action 2–60 min [9]
Elimination half-life 7–46 hours
Duration of action 6–48 hours [9]
Excretion Urine
Identifiers
  • 1-(1-Phenylcyclohexyl)piperidine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.150.427 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H25N
Molar mass 243.394 g·mol−1
3D model (JSmol)
Melting point 46.5 °C (115.7 °F)
Boiling point 136 °C (277 °F)
  • c1ccccc1C2(CCCCC2)N3CCCCC3
  • InChI=1S/C17H25N/c1-4-10-16(11-5-1)17(12-6-2-7-13-17)18-14-8-3-9-15-18/h1,4-5,10-11H,2-3,6-9,12-15H2 Yes check.svgY
  • Key:JTJMJGYZQZDUJJ-UHFFFAOYSA-N Yes check.svgY
Data page
Phencyclidine (data page)
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Phencyclidine or phenylcyclohexyl piperidine (PCP), also known in its use as a street drug as angel dust among other names, is a dissociative anesthetic mainly used recreationally for its significant mind-altering effects. [1] [7] PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. [7] [10] [11] As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. [7] [8] [10] It may also be mixed with cannabis or tobacco. [1] [7]

Contents

Adverse effects may include seizures, coma, addiction, and an increased risk of suicide. [10] Flashbacks may occur despite stopping usage. [11] Chemically, PCP is a member of the arylcyclohexylamine class, and pharmacologically, it is a dissociative anesthetic. [7] [12] [13] PCP works primarily as an NMDA receptor antagonist. [12]

PCP is most commonly used in the United States. [14] While usage peaked in the US in the 1970s, [15] between 2005 and 2011 an increase in visits to emergency departments as a result of the drug occurred. [10] As of 2017 in the United States, about 1% of people in 12th grade reported using PCP in the prior year while 2.9% of those over the age of 25 reported using it at some point in their lives. [16]

Recreational uses

Illicit PCP in several forms seized by the DEA. Phencyclidine (PCP).jpg
Illicit PCP in several forms seized by the DEA.

Phencyclidine is used for its ability to induce a dissociative state. [17]

Effects

Behavioral effects can vary by dosage. Low doses produce a numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses (5–10 mg intranasal, or 0.01–0.02 mg/kg intramuscular or intravenous) will produce analgesia and anesthesia. High doses may lead to convulsions. [18] The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking. [19]

Psychological effects include severe changes in body image, loss of ego boundaries, paranoia, and depersonalization. Psychosis, agitation and dysphoria, hallucinations, blurred vision, euphoria, and suicidal impulses are also reported, as well as occasional aggressive behavior. [20] [21] : 48–49  [18] Like many other drugs, PCP has been known to alter mood states in an unpredictable fashion, causing some individuals to become detached, and others to become animated. PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind. [8]

Studies by the Drug Abuse Warning Network in the 1970s show that media reports of PCP-induced violence are greatly exaggerated and that incidents of violence are unusual and often limited to individuals with reputations for aggression regardless of drug use. [21] : 48  Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized. [22] Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling one's own teeth. [21] : 48  [22] These effects were not noted in its medicinal use in the 1950s and 1960s, however, and reports of physical violence on PCP have often been shown to be unfounded. [23] [24]

Recreational doses of the drug also occasionally appear to induce a psychotic state, with emotional and cognitive impairment that resembles a schizophrenic episode. [25] [26] Users generally report feeling detached from reality. [27]

Symptoms are summarized by the mnemonic device RED DANES: rage, erythema (redness of skin), dilated pupils, delusions, amnesia, nystagmus (oscillation of the eyeball when moving laterally), excitation, and skin dryness. [28]

Addiction

PCP is self-administered and induces ΔFosB expression in the D1-type medium spiny neurons of the nucleus accumbens, [4] [29] and accordingly, excessive PCP use is known to cause addiction. [4] PCP's rewarding and reinforcing effects are at least partly mediated by blocking the NMDA receptors in the glutamatergic inputs to D1-type medium spiny neurons in the nucleus accumbens. [4] PCP has been shown to produce conditioned place aversion and conditioned place preference in animal studies. [30]

Schizophrenia

A 2019 review found that the transition rate from a diagnosis of hallucinogen-induced psychosis (which included PCP) to that of schizophrenia was 26%. This was lower than cannabis-induced psychosis (34%) but higher than amphetamine (22%), opioid (12%), alcohol (10%), and sedative (9%) induced psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%. [31]

Methods of administration

PCP is easily accessible because of the various routes of administration available. Most commonly, the powder form of the drug is snorted. PCP can also be orally ingested, injected subcutaneously or intravenously, or smoked laced with marijuana or cigarettes. [32]

Management of intoxication

Management of PCP intoxication mostly consists of supportive care – controlling breathing, circulation, and body temperature – and, in the early stages, treating psychiatric symptoms. [34] [35] [36] Benzodiazepines, such as lorazepam, are the drugs of choice to control agitation and seizures (when present). Typical antipsychotics such as phenothiazines and haloperidol have been used to control psychotic symptoms, but may produce many undesirable side effects – such as dystonia – and their use is therefore no longer preferred; phenothiazines are particularly risky, as they may lower the seizure threshold, worsen hyperthermia, and boost the anticholinergic effects of PCP. [34] [35] If an antipsychotic is given, intramuscular haloperidol has been recommended. [36] [37] [38]

Forced acid diuresis (with ammonium chloride or, more safely, ascorbic acid) may increase clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure. [34] [35] [36] However, it is now known that only around 10% of a dose of PCP is removed by the kidneys, which would make increased urinary clearance of little consequence; furthermore, urinary acidification is dangerous, as it may induce acidosis and worsen rhabdomyolysis (muscle breakdown), a not-unusual manifestation of PCP toxicity. [34] [35]

Pharmacology

Pharmacodynamics

Phencyclidine [39] [40]
SiteKi (nM)ActionSpeciesRef
NMDA Tooltip N-Methyl-D-aspartate receptor44–59AntagonistHuman [41] [42]
MOR Tooltip μ-Opioid receptor>10,000NDHuman [41]
DOR Tooltip δ-Opioid receptor>10,000NDHuman [41]
KOR Tooltip κ-Opioid receptor>10,000NDHuman [41]
NOP Tooltip Nociceptin receptor>10,000NDHuman [41]
σ1 >10,000AgonistGuinea pig [41] [43]
σ2 136AgonistRat [41]
D2 >10,000NDHuman [41]
   D2High 2.7–4.3
144 (EC50)		Partial AgonistRat/human
Human		 [44] [45]
[46]
5-HT2A >10,000NDHuman [41]
   5-HT2AHigh ≥5,000Agonist?Rat [45] [47]
SERT Tooltip Serotonin transporter2,234InhibitorHuman [41]
NET Tooltip Norepinephrine transporter>10,000InhibitorHuman [41]
DAT Tooltip Dopamine transporter>10,000InhibitorHuman [41]
PCP2 154NDHuman [42]
[3H]5-HT uptake 1,424 (IC50)InhibitorRat [48]
[3H]NIS binding 16,628 (IC50)InhibitorRat [48]
[3H]DA uptake 347 (IC50)InhibitorRat [48]
[3H]CFT binding 1,547 (IC50)InhibitorRat [48]
Values are Ki (nM). The smaller the value, the more strongly the drug binds to the site.

PCP is well known for its primary action on the NMDA receptor, an ionotropic glutamate receptor. [49] [46] As such, PCP is a noncompetitive NMDA receptor antagonist. The role of NMDAR antagonism in the effect of PCP, ketamine, and related dissociative agents was first published in the early 1980s by David Lodge [50] and colleagues. [51] Other NMDA receptor antagonists include ketamine, [52] tiletamine, [53] dextromethorphan, [54] nitrous oxide, and dizocilpine (MK-801).

Research also indicates that PCP inhibits nicotinic acetylcholine receptors (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors [55] and NMDA receptors. [56] Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain. [57] These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the hippocampus [58] and cerebellum [59] thus potentially leading to memory loss as one of the effects of prolonged use. Acute effects on the cerebellum manifest as changes in blood pressure, breathing rate, pulse rate, and loss of muscular coordination during intoxication. [11]

PCP, like ketamine, also acts as a potent dopamine D2High receptor partial agonist in rat brain homogenate [46] and has affinity for the human cloned D2High receptor. [60] This activity may be associated with some of the other more psychotic features of PCP intoxication, which is evidenced by the successful use of D2 receptor antagonists (such as haloperidol) in the treatment of PCP psychosis. [61]

In addition to its well explored interactions with NMDA receptors, PCP has also been shown to inhibit dopamine reuptake, and thereby leads to increased extracellular levels of dopamine and hence increased dopaminergic neurotransmission. [62] However, PCP has little affinity for the human monoamine transporters, including the dopamine transporter (DAT). [41] Instead, its inhibition of monoamine reuptake may be mediated by interactions with allosteric sites on the monoamine transporters. [41] PCP is notably a high-affinity ligand of the PCP site 2 (Ki = 154 nM), a not-well-characterized site associated with monoamine reuptake inhibition. [42]

Studies on rats indicate that PCP interacts indirectly with opioid receptors (endorphin and enkephalin) to produce analgesia. [63]

A binding study assessed PCP at 56 sites including neurotransmitter receptors and transporters and found that PCP had Ki values of >10,000 nM at all sites except the dizocilpine (MK-801) site of the NMDA receptor (Ki = 59 nM), the σ2 receptor (PC12) (Ki = 136 nM), and the serotonin transporter (Ki = 2,234 nM). [41] The study notably found Ki values of >10,000 nM for the D2 receptor, the opioid receptors, the σ1 receptor, and the dopamine and norepinephrine transporters. [41] These results suggest that PCP is a highly selective ligand of the NMDAR and σ2 receptor. [41] However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake. [41]

Mechanism of action

Phencyclidine is a noncompetitive NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia without causing cardiorespiratory depression. [64] [20] NMDA is an excitatory receptor in the brain, when activated normally the receptor acts as an ion channel and there is an influx of positive ions through the channel to cause nerve cell depolarisation. Phencyclidine inhibits the NMDA receptor by binding to the specific PCP binding site located within the ion channel. [65] The PCP binding site is within close proximity to the magnesium blocking site, which may explain the similar inhibitory effects. [66] Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction. [67] Binding is also controlled by the gating mechanism of the ion channel. Because the PCP site is located within the ion channel, a coagonist such as glycine must bind and open the channel in order for PCP to enter, bind to the PCP site, and block the channel. [68]

Neurotoxicity

Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of brain damage called Olney's lesions in rats. [69] [70] Studies conducted on rats showed that high doses of the NMDA receptor antagonist dizocilpine caused reversible vacuoles to form in certain regions of the rats' brains. All studies of Olney's lesions have only been performed on non-human animals and may not apply to humans. One unpublished study by Frank Sharp reportedly showed no damage by the NDMA antagonist ketamine, a structurally similar drug, far beyond recreational doses, [71] but due to the study never having been published, its validity is controversial.

PCP has also been shown to cause schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate levels in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue. [72] It also induces symptoms in humans that mimic schizophrenia. [73] PCP not only produced symptoms similar to schizophrenia, it also yielded electroencephalogram changes in the thalamocortical pathway (increased delta decreased alpha) and in the hippocampus (increase theta bursts) that were similar to those in schizophrenia. [74] PCP-induced augmentation of dopamine release may link the NMDA and dopamine hypotheses of schizophrenia. [75]

Pharmacokinetics

Conversion of PCP into PC and piperidine by heat. PCP2PCandPOPERIDINE.png
Conversion of PCP into PC and piperidine by heat.

PCP is both water and lipid soluble and is therefore distributed throughout the body quickly. [66] PCP is metabolized into PCHP, PPC and PCAA. The drug is metabolized 90% by oxidative hydroxylation in the liver during the first pass. Metabolites are glucuronidated and excreted in the urine. Nine percent of ingested PCP is excreted in its unchanged form. [20]

When smoked, some of the compound is broken down by heat into 1-phenylcyclohexene (PC) and piperidine.

The time taken before the effects of PCP manifest is dependent on the route of administration. The onset of action for inhalation occurs in 2–5 minutes, whereas the effects may take 15 to 60 minutes when ingested orally. [20]

Chemistry

PCP is an arylcyclohexylamine.

Analogues

Possible analogues of PCP ACHA SAR.png
Possible analogues of PCP

Fewer than 30 different analogs of PCP were reported as being used as a street drug during the 1970s and 1980s, mainly in the United States. [51] Only of a few of these compounds were widely used including rolicyclidine (PCPy), eticyclidine (PCE), and tenocyclidine (TCP). [51] Less common analogs include 3-HO-PCP, 3-MeO-PCMo, and 3-MeO-PCP.

The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP derivatives. All of these derivatives are likely to share some of their psychoactive effects with PCP itself, although a range of potencies and varying mixtures of anesthetic, dissociative, and stimulant effects are known, depending on the particular drug and its substituents. In some countries such as the United States, Australia, and New Zealand, all of these compounds would be considered controlled substance analogs of PCP under the Federal Analog Act and are hence illegal drugs if sold for human consumption. [76] [77]

History

Phencyclidine was initially discovered in 1926 by Arthur Kötz  [ de ] and his student Paul Merkel as a product of a Grignard reaction of 1-piperidinocyclohexancarbonitrile. [78]

It was again made in 1956 and brought to market as an anesthetic medication. [74] [13] [79] [78] [80] Its use in humans was disallowed in the United States in 1965 due to the high rates of side effects, while its use in animals was disallowed in 1978. [1] [13] [81] Moreover, ketamine was discovered and was better tolerated as an anesthetic. [81]

PCP is classified as a schedule II drug in the United States. [1] A number of derivatives of PCP have been sold for recreational and non-medical use. [51]

Society and culture

Regulation

PCP is a Schedule II substance in the United States and its ACSCN is 7471. [82] Its manufacturing quota for 2014 was 19 grams. [83]

It is a Schedule I drug by the Controlled Drugs and Substances act in Canada, a List I drug of the Opium Law in the Netherlands, and a Class A substance in the United Kingdom. [84]

Frequency of use

PCP began to emerge as a recreational drug in major cities in the United States in the 1960s. [10] In 1978, People magazine and Mike Wallace of 60 Minutes called PCP the country's "number one" drug problem. Although recreational use of the drug had always been relatively low, it began declining significantly in the 1980s. In surveys, the number of high school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990. [21] : 46–49 

Cultural depictions

Jean-Michel Basquiat depicted two angel dust users in his 1982 painting Dustheads . [85]

In Vivienne Medrano's adult animated musical comedy television series Hazbin Hotel, Angel Dust is an adult film star in Hell and one of the main protagonists. [86] He is known to struggle with addiction to phencyclidine, currently and during his time on earth. Additionally his canon cause of death is overdose by phencyclidine, naming himself after the drug. [87]

Related Research Articles

<span class="mw-page-title-main">Ketamine</span> Dissociative anesthetic and anti-depressant

Ketamine is a dissociative anesthetic used medically for induction and maintenance of anesthesia. It is also used as a treatment for depression and pain management. It is a novel compound that was derived from phencyclidine in 1962 in pursuit of a safer anesthetic with fewer hallucinogenic effects.

<span class="mw-page-title-main">Psychopharmacology</span> Study of the effects of psychoactive drugs

Psychopharmacology is the scientific study of the effects drugs have on mood, sensation, thinking, behavior, judgment and evaluation, and memory. It is distinguished from neuropsychopharmacology, which emphasizes the correlation between drug-induced changes in the functioning of cells in the nervous system and changes in consciousness and behavior.

Dissociatives, colloquially dissos, are a subclass of hallucinogens that distort perception of sight and sound and produce feelings of detachment – dissociation – from the environment and/or self. Although many kinds of drugs are capable of such action, dissociatives are unique in that they do so in such a way that they produce hallucinogenic effects, which may include dissociation, a general decrease in sensory experience, hallucinations, dream-like states or anesthesia. Despite most dissociatives' main mechanism of action being tied to NMDA receptor antagonism, some of these substances, which are nonselective in action and affect the dopamine and/or opioid systems, may be capable of inducing more direct and repeatable euphoria or symptoms which are more akin to the effects of typical "hard drugs" or common drugs of abuse. This is likely why dissociatives are considered to be addictive with a fair to moderate potential for abuse, unlike psychedelics. Despite some dissociatives, such as phencyclidine (PCP) possessing stimulating properties, most dissociatives seem to have a general depressant effect and can produce sedation, respiratory depression, nausea, disorientation, analgesia, anesthesia, ataxia, cognitive and memory impairment as well as amnesia.

The dopamine hypothesis of schizophrenia or the dopamine hypothesis of psychosis is a model that attributes the positive symptoms of schizophrenia to a disturbed and hyperactive dopaminergic signal transduction. The model draws evidence from the observation that a large number of antipsychotics have dopamine-receptor antagonistic effects. The theory, however, does not posit dopamine overabundance as a complete explanation for schizophrenia. Rather, the overactivation of D2 receptors, specifically, is one effect of the global chemical synaptic dysregulation observed in this disorder.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

<span class="mw-page-title-main">Dizocilpine</span> Chemical compound

Dizocilpine (INN), also known as MK-801, is a pore blocker of the NMDA receptor, a glutamate receptor, discovered by a team at Merck in 1982. 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. Dizocilpine binds inside the ion channel of the receptor at several of PCP's binding sites thus preventing the flow of ions, including 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 probably has dissociative anesthetic properties, but it is not used clinically for this purpose because of the discovery of brain lesions, called Olney's lesions (see below), in laboratory rats. Dizocilpine is also associated with a number of negative side effects, including cognitive disruption and psychotic-spectrum reactions. It inhibits the induction of long term potentiation and has been found to impair the acquisition of difficult, but not easy, learning tasks in rats and primates. Because of these effects of dizocilpine, the NMDA receptor pore blocker ketamine is used instead 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 uncompetitive NMDA receptor antagonist in animal models to mimic psychosis for experimental purposes.

<span class="mw-page-title-main">Orphenadrine</span> Muscle relaxant drug

Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class; it is closely related to diphenhydramine. It is a muscle relaxant that is used to treat muscle pain and to help with motor control in Parkinson's disease, but has largely been superseded by newer drugs. It is considered a dirty drug due to its multiple mechanisms of action in different pathways. It was discovered and developed in the 1940s.

<span class="mw-page-title-main">Dextromethorphan</span> Morphinan antitussive and dissociative drug

Dextromethorphan (DXM) is a cough suppressant used in many cough and cold medicines. It affects serotonin, norepinephrine, NMDA, and sigma-1 receptors in the brain, all of which have been implicated in the pathophysiology of depression. In 2022, the FDA approved the combination dextromethorphan/bupropion to serve as a rapid acting antidepressant in patients with major depressive disorder.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for human and non-human animals; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Tenocyclidine</span> Chemical compound

Tenocyclidine (TCP) is a dissociative anesthetic with psychostimulant effects. It was discovered by a team at Parke-Davis in the late 1950s. It is similar in effects to phencyclidine (PCP) 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 receptors. Because of its high affinity for the PCP site of the NMDA receptor complex, the 3H radiolabelled form of TCP is widely used in research into NMDA receptors.

<span class="mw-page-title-main">Etoxadrol</span> Chemical compound

Etoxadrol (CL-1848C) is a dissociative anaesthetic drug that has been found to be an NMDA antagonist and produce 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 in the late 1970s after patients reported side effects such as nightmares and hallucinations.

The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia 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. While thought to be more proximal to the root causes of schizophrenia, it does not negate the dopamine hypothesis, and the two may be ultimately brought together by circuit-based models. The development of the hypothesis allowed for the integration of the GABAergic and oscillatory abnormalities into the converging disease model and made it possible to discover the causes of some disruptions.

<span class="mw-page-title-main">Reuptake inhibitor</span> Type of drug

Reuptake inhibitors (RIs) are a type of reuptake modulators. It is a drug that inhibits the plasmalemmal transporter-mediated reuptake of a neurotransmitter from the synapse into the pre-synaptic neuron. This leads to an increase in extracellular concentrations of the neurotransmitter and an increase in neurotransmission. Various drugs exert their psychological and physiological effects through reuptake inhibition, including many antidepressants and psychostimulants.

Hallucinogens are a large and diverse class of psychoactive drugs that can produce altered states of consciousness characterized by major alterations in thought, mood, and perception as well as other changes. Most hallucinogens can be categorized as either being psychedelics, dissociatives, or deliriants.

<span class="mw-page-title-main">Benocyclidine</span> Chemical compound

Benocyclidine, also known as benzo​thiophenyl​cyclo​hexylpiperidine (BTCP), is a psychoactive recreational drug of the arylcyclohexylamine class which is related to phencyclidine (PCP). It was first described in a patent application naming Marc Caron and colleagues at Duke University in 1997.

<span class="mw-page-title-main">LY-379,268</span> Chemical compound

LY-379,268 is a drug that is used in neuroscience research, which acts as a potent and selective agonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">Arylcyclohexylamine</span> Class of chemical compounds

Arylcyclohexylamines, also known as arylcyclohexamines or arylcyclohexanamines, are a chemical class of pharmaceutical, designer, and experimental drugs.

<span class="mw-page-title-main">3-MeO-PCP</span> Chemical compound

3-Methoxyphencyclidine (3-MeO-PCP) is a dissociative hallucinogen of the arylcyclohexylamine class related to phencyclidine (PCP) which has been sold online as a designer drug. It acts mainly as an NMDA receptor antagonist, though it has also been found to interact with the sigma σ1 receptor and the serotonin transporter. The drug does not possess any opioid activity nor does it act as a dopamine reuptake inhibitor.

<span class="mw-page-title-main">Methoxetamine</span> Dissociative drug

Methoxetamine, abbreviated as MXE, is a dissociative hallucinogen that has been sold as a designer drug. It differs from many dissociatives such as ketamine and phencyclidine (PCP) that were developed as pharmaceutical drugs for use as general anesthetics in that it was designed specifically to increase the antidepressant effects of ketamine.

<span class="mw-page-title-main">Metaphit</span> Chemical compound

Metaphit is a research chemical that acts as an acylator of NMDARAn, sigma and DAT binding sites in the CNS. It is the m-isothiocyanate derivative of phencyclidine (PCP) and binds irreversibly to the PCP binding site on the NMDA receptor complex. However, later studies suggest the functionality of metaphit is mediated by sites not involved in PCP-induced passive avoidance deficit, and not related to the NMDA receptor complex. Metaphit was also shown to prevent d-amphetamine induced hyperactivity, while significantly depleting dopamine content in the nucleus accumbens. Metaphit was the first acylating ligand used to study the cocaine receptor. It is a structural isomer of the similar research compound fourphit, as it and metaphit both are isothiocyanate substituted derivatives of an analogous scaffold shared with PCP.

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