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 Psychological: Moderate [2]
Addiction
liability 		Variable, reported from low to high [3] [2]
Drug class NMDA receptor antagonists; General anesthetics; Dissociative hallucinogens [4]
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 [5]
Elimination half-life 7–46 hours
Duration of action 6–48 hours [5]
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] [4] PCP may cause hallucinations, distorted perceptions of sounds, and violent behavior. [4] [6] [7] As a recreational drug, it is typically smoked, but may be taken by mouth, snorted, or injected. [4] [8] [6] It may also be mixed with cannabis or tobacco. [1] [4]

Contents

Adverse effects may include seizures, coma, addiction, and an increased risk of suicide. [6] Flashbacks may occur despite stopping usage. [7] Chemically, PCP is a member of the arylcyclohexylamine class, and pharmacologically, it is a dissociative anesthetic. [4] [9] [10] PCP works primarily as an NMDA receptor antagonist. [9]

PCP is most commonly used in the US. [11] While usage peaked in the US in the 1970s, [12] between 2005 and 2011, an increase in visits to emergency departments as a result of the drug occurred. [6] As of 2022, in the US, about 0.7% of 12th grade students reported using PCP in the prior year, while 1.7% of people in the US over age 25 reported using it at some point in their lives. [13]

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. [14]

Effects

Behavioral effects can vary by dosage. Low doses produce 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. [15] The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking. [16]

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. [17] [18] : 48–49  [15] Like many other drugs, PCP has been known to alter mood states unpredictably, 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. [18] : 48  Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized. [19] Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling out one's teeth. [18] : 48  [19] These effects were not noted in its medicinal use in the 1950s and 1960s, however, reports of physical violence on PCP have often been shown to be unfounded. [20] [21]

Recreational doses of the drug also occasionally appear to induce a psychotic state, with emotional and cognitive impairment that resembles a schizophrenic episode. [22] [23] Users generally report feeling detached from reality. [24]

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. [25]

Addiction

PCP is self-administered and induces ΔFosB expression in the D1-type medium spiny neurons of the nucleus accumbens, [3] [26] and accordingly, excessive PCP use is known to cause addiction. [3] 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. [3] PCP has been shown to produce conditioned place aversion and conditioned place preference in animal studies. [27]

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%. [28]

Methods of administration

PCP has multiple routes of administration. 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. [29]

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. [31] [32] [33] 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. [31] [32] If an antipsychotic is given, intramuscular haloperidol has been recommended. [33] [34] [35]

Forced acid diuresis (with ammonium chloride or, more safely, ascorbic acid) may increase the clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure. [31] [32] [33] 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. [31] [32]

Pharmacology

Pharmacodynamics

Phencyclidine [36] [37]
SiteKi (nM)ActionSpeciesRef
NMDA Tooltip N-Methyl-D-aspartate receptor59AntagonistHuman [38] [39]
MOR Tooltip μ-Opioid receptor>10,000NDHuman [38]
DOR Tooltip δ-Opioid receptor>10,000NDHuman [38]
KOR Tooltip κ-Opioid receptor>10,000NDHuman [38]
NOP Tooltip Nociceptin receptor>10,000NDHuman [38]
σ1 >10,000AgonistGuinea pig [38] [40]
σ2 136AgonistRat [38]
D2 >10,000NDHuman [38]
   D2High 2.7–4.3
144 (EC50)		Partial AgonistRat/human
Human		 [41] [42]
[43]
5-HT2A >10,000NDHuman [38]
   5-HT2AHigh ≥5,000Partial

Agonist

Rat [42] [44]
SERT Tooltip Serotonin transporter2,234InhibitorHuman [38]
NET Tooltip Norepinephrine transporter>10,000InhibitorHuman [38]
DAT Tooltip Dopamine transporter>10,000InhibitorHuman [38]
PCP2 154agonistHuman [39]
[3H]5-HT uptake 1,424 (IC50)InhibitorRat [45]
[3H]NIS binding 16,628 (IC50)InhibitorRat [45]
[3H]DA uptake 347 (IC50)InhibitorRat [45]
[3H]CFT binding 1,547 (IC50)InhibitorRat [45]
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. [46] [43] As such, PCP is a non-competitive 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 [47] and colleagues. [48] Other NMDA receptor antagonists include ketamine, [49] tiletamine, [50] dextromethorphan, [51] 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 [52] and NMDA receptors. [53] Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence the postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain. [54] These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the hippocampus [55] and cerebellum [56] 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. [7]

PCP, like ketamine, also acts as a potent dopamine D2High receptor partial agonist in rat brain homogenate [43] and has affinity for the human cloned D2High receptor. [57] 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. [58]

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. [59] However, PCP has little affinity for the human monoamine transporters, including the dopamine transporter (DAT). [38] Instead, its inhibition of monoamine reuptake may be mediated by interactions with allosteric sites on the monoamine transporters. [38] 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. [39]

Studies on rats indicate that PCP interacts indirectly with opioid receptors (endorphin and enkephalin) to produce analgesia. [60]

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). [38] 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. [38] These results suggest that PCP is a highly selective ligand of the NMDAR and σ2 receptor. [38] However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake. [38]

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. [61] [17] 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. [62] The PCP binding site is within close proximity to the magnesium blocking site, which may explain the similar inhibitory effects. [63] Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction. [64] 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 for PCP to enter, bind to the PCP site, and block the channel. [65]

Neurotoxicity

Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of brain damage called Olney's lesions in rats. [66] [67] 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 NMDA antagonist ketamine, a structurally similar drug, far beyond recreational doses, [68] 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. [69] It also induces symptoms in humans that mimic schizophrenia. [70] 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. [71] PCP-induced augmentation of dopamine release may link the NMDA and dopamine hypotheses of schizophrenia. [72]

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. [63] 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. [17]

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. [17]

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. [48] Only of a few of these compounds were widely used including rolicyclidine (PCPy), eticyclidine (PCE), and tenocyclidine (TCP). [48] 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 the United States, 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. [73] [74]

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. [75]

It was again synthesized in 1956 by chemist H Victor Maddox and brought to market as an anesthetic medication by pharmaceutical company Parke-Davis, now a subsidiary of Pfizer. [71] [10] [76] [75] [77] Its use in humans was disallowed in the US in 1965 due to the high rates of side effects, while its use in animals was disallowed in 1978. [1] [10] [78] Moreover, ketamine was discovered and was better tolerated as an anesthetic. [78]

PCP is classified as a schedule II drug in the US. [1] Derivatives of PCP have been sold for recreational and non-medical use. [48]

Society and culture

Regulation

PCP is a Schedule II substance in the US. The Administrative Controlled Substances Code Number (ACSCN) for PCP is 7471. [79] Its manufacturing quota for 2014 was 19 grams (0.67 oz). [80] 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 UK. [81]

Frequency of use

PCP began to emerge as a recreational drug in major cities in the US in the 1960s. [6] In 1978, People magazine and Mike Wallace of the TV news program 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. [18] : 46–49 

Cultural depictions

Jean-Michel Basquiat depicted two angel dust users in his 1982 painting Dustheads . [82]

Tsukasa Hojo's 1985 manga City Hunter features a drug, Angel Dust, presumably a reference to PCP's street name. The related 2023 animated film, City Hunter: Angel Dust , more directly moved the franchise's angel dust into the realm of fantasy, as it is portrayed as a science fiction nanomachine serum developed by a biotech company to create super-soldiers with a tendency to drive them berserk, side-stepping the real-life PCP. [83]

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. [84] He is known to struggle with addiction to phencyclidine, during his lifetime as well as the afterlife. His cause of death was an overdose of phencyclidine, so renamed himself in the afterlife after the drug. [85]

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 in pain management. Ketamine is an NMDA receptor antagonist which accounts for most of its psychoactive 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> Cough suppressant, antidepressant, and dissociative drug

Dextromethorphan, sold under the brand name Robitussin among others, is a cough suppressant used in many cough and cold medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropion to serve as a rapid-acting antidepressant in people 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 humans and 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 benzothiophenylcyclohexylpiperidine (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 has been used across Europe and the United States. In some cases, consumption has been known to be fatal. 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 (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.

References

  1. 1 2 3 4 5 "PCP Fast Facts". justice.gov. National Drug Intelligence Center. 2003. Archived from the original on 14 August 2021. Retrieved 19 February 2018.
  2. 1 2 Stobo JD, Traill TA, Hellmann DB, Ladenson PW, Petty BG (1996). The Principles and Practice of Medicine. McGraw Hill Professional. p. 933. ISBN   9780071383653 – via Google Books. high abuse liability
  3. 1 2 3 4 Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 374–375. ISBN   9780071481274.
  4. 1 2 3 4 5 6
  5. 1 2 Riviello RJ (2010). Manual of forensic emergency medicine : a guide for clinicians. Sudbury, Massachusetts: Jones and Bartlett Publishers. pp. 41–42. ISBN   9780763744625 – via Google Books.
  6. 1 2 3 4 5 Bush DM (2013). "Emergency Department Visits Involving Phencyclidine (PCP)". The CBHSQ Report. Rockville, Maryland: Substance Abuse and Mental Health Services Administration. PMID   27656747. PCP can lead to hostile behavior that may result in episodes of extreme violence
  7. 1 2 3 "Hallucinogens". National Institute on Drug Abuse. January 2016. Retrieved 20 February 2018.
  8. 1 2 "NIDA InfoFacts: Hallucinogens – LSD, Peyote, Psilocybin, and PCP". drugabuse.gov. National Institute on Drug Abuse . Retrieved 2018-02-19.
  9. 1 2 Marion NE, Oliver WM (2014). Drugs in American Society: An Encyclopedia of History, Politics, Culture, and the Law. ABC-CLIO. p. 732. ISBN   9781610695961 – via Google Books.
  10. 1 2 3 Zedeck BE, Zedeck MS (2007). Forensic Pharmacology. Infobase Publishing. p. 97. ISBN   9781438103822.
  11. ↑ "PCP". ginad.org. Archived from the original on 2018-09-10. Retrieved 2018-02-20.
  12. ↑ "PCP". cesar.umd.edu. Archived from the original on 12 March 2010. Retrieved 20 February 2018.
  13. ↑ "Hallucinogens". drugabuse.gov. National Institute on Drug Abuse. Archived from the original on 3 June 2020. Retrieved 20 February 2018.
  14. ↑ Millan MJ, Brocco M, Gobert A, Joly F, Bervoets K, Rivet J, et al. (December 1999). "Contrasting mechanisms of action and sensitivity to antipsychotics of phencyclidine versus amphetamine: importance of nucleus accumbens 5-HT2A sites for PCP-induced locomotion in the rat". The European Journal of Neuroscience. 11 (12): 4419–32. doi:10.1046/j.1460-9568.1999.00858.x. PMID   10594669. S2CID   43150509.
  15. 1 2 Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.
  16. ↑ Chudler EM. "Neuroscience for Kids – PCP". Neuroscience for Kids. Retrieved 2011-01-26.
  17. 1 2 3 4 Bey T, Patel A (February 2007). "Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug". The California Journal of Emergency Medicine. 8 (1): 9–14. PMC   2859735 . PMID   20440387.
  18. 1 2 3 4 Inciardi JA (1992). The War on Drugs II. Mayfield Publishing Company. ISBN   978-1-55934-016-8.
  19. 1 2 Morgan JP, Kagan D (July 1980). "The Dusting of America: The Image of Phencyclidine (PCP) in the Popular Media". Journal of Psychedelic Drugs. 12 (3–4): 195–204. doi:10.1080/02791072.1980.10471426. PMID   7431414.
  20. ↑ Brecher M, Wang BW, Wong H, Morgan JP (December 1988). "Phencyclidine and violence: clinical and legal issues". Journal of Clinical Psychopharmacology. 8 (6): 397–401. doi:10.1097/00004714-198812000-00003. PMID   3069880. S2CID   33659160.
  21. ↑ Wish ED (1986). "PCP and crime: just another illicit drug?". NIDA Research Monograph. 64: 174–89. PMID   3086733.
  22. ↑ Uchida M, Hida H, Mori K, Yoshimi A, Kitagaki S, Yamada K, et al. (August 2019). "Functional roles of the glial glutamate transporter (GLAST) in emotional and cognitive abnormalities of mice after repeated phencyclidine administration". Eur Neuropsychopharmacol. 29 (8): 918–24. doi: 10.1016/j.euroneuro.2019.06.005 . PMID   31303267. S2CID   195887087.
  23. ↑ Luisada PV (August 1978). Petersen RC, Stillman RC (eds.). "The phencyclidine psychosis: phenomenology and treatment" (PDF). NIDA Research Monograph (21). National Institute on Drug Abuse: 241–253. PMID   101872.
  24. ↑ Pender JW (October 1972). "Dissociative anesthesia". California Medicine. 117 (4): 46–47. PMC   1518731 . PMID   18730832.
  25. ↑ Giannini AJ (1997). Drugs of Abuse (Second ed.). Los Angeles: Practice Management Information Corp. p. 126. ISBN   978-1-57066-053-5.
  26. ↑ Nestler EJ (October 12, 2008). "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philos. Trans. R. Soc. Lond. B Biol. Sci. 363 (1507): 3245–3255. doi:10.1098/rstb.2008.0067. PMC   2607320 . PMID   18640924.Nestler EJ (October 2008). "Table 1: Drugs of abuse known to induce ΔFosB in nucleus accumbens after chronic administration". Philos. Trans. R. Soc. Lond. B Biol. Sci. 363 (1507): 3245–55. doi:10.1098/rstb.2008.0067. PMC   2607320 . PMID   18640924.
  27. ↑ Noda Y, Nabeshima T (September 1998). "Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task". Methods and Findings in Experimental and Clinical Pharmacology. 20 (7): 607–11. doi:10.1358/mf.1998.20.7.485726. PMID   9819806.
  28. ↑ Murrie B, Lappin J, Large M, Sara G (April 2020). "Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis". Schizophrenia Bulletin. 46 (3): 505–516. doi: 10.1093/schbul/sbz102 . PMC   7147575 . PMID   31618428.
  29. 1 2 3 4 Bertron JL, Seto M, Lindsley CW (October 2018). "DARK Classics in Chemical Neuroscience: Phencyclidine (PCP)". ACS Chemical Neuroscience. 9 (10): 2459–2474. doi:10.1021/acschemneuro.8b00266. PMID   29953199. S2CID   49603581.
  30. ↑ "Fry Fast Facts". National Drug Intelligence Center. Archived from the original on 2021-04-17. Retrieved 2017-01-15.
  31. 1 2 3 4 Helman RS, Habal R (October 6, 2008). "Phencyclidine Toxicity". eMedicine . Retrieved on November 3, 2008.
  32. 1 2 3 4 Olmedo R (2002). "Chapter 69: Phencyclidine and ketamine". In Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS (eds.). Goldfrank's Toxicologic Emergencies. New York: McGraw-Hill. pp. 1034–1041. ISBN   978-0-07-136001-2.
  33. 1 2 3 Milhorn HT (Apr 1991). "Diagnosis and management of phencyclidine intoxication". American Family Physician. 43 (4): 1293–302. PMID   2008817.
  34. ↑ Giannini AJ, Price WA (1985). "PCP: Management of acute intoxication". Medical Times. 113 (9): 43–49.
  35. ↑ Giannini AJ, Eighan MS, Loiselle RH, Giannini MC (Apr 1984). "Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis". Journal of Clinical Pharmacology. 24 (4): 202–4. doi:10.1002/j.1552-4604.1984.tb01831.x. PMID   6725621. S2CID   42278510.
  36. ↑ Roth BL, Driscol J. "PDSP Ki Database". Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved 14 August 2017.
  37. ↑ Berton JL, Seto M, Lindsley CW (June 2018). "DARK Classics in Chemical Neuroscience: Phencyclidine (PCP)". ACS Chem Neurosci. 9 (10): 2459–2474. doi:10.1021/acschemneuro.8b00266. PMID   29953199. S2CID   49603581.
  38. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, et al. (2013). "The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor". PLOS ONE. 8 (3): e59334. Bibcode:2013PLoSO...859334R. doi: 10.1371/journal.pone.0059334 . PMC   3602154 . PMID   23527166.
  39. 1 2 3 Rothman RB (1994). "PCP site 2: a high affinity MK-801-insensitive phencyclidine binding site". Neurotoxicol Teratol. 16 (4): 343–53. doi:10.1016/0892-0362(94)90022-1. PMID   7968938.
  40. ↑ Frohlich J, Van Horn JD (2014). "Reviewing the ketamine model for schizophrenia". J. Psychopharmacol. (Oxford). 28 (4): 287–302. doi:10.1177/0269881113512909. PMC   4133098 . PMID   24257811.
  41. ↑ Seeman P, Guan HC (2008). "Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia". Synapse. 62 (11): 819–28. doi:10.1002/syn.20561. PMID   18720422. S2CID   206519749.
  42. 1 2 Kapur S, Seeman P (2002). "NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2)receptors-implications for models of schizophrenia". Mol. Psychiatry. 7 (8): 837–44. doi: 10.1038/sj.mp.4001093 . PMID   12232776.
  43. 1 2 3 Seeman P, Guan HC, Hirbec H (2009). "Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil". Synapse. 63 (8): 698–704. doi:10.1002/syn.20647. PMID   19391150. S2CID   17758902.
  44. ↑ Rabin RA, Doat M, Winter JC (2000). "Role of serotonergic 5-HT2A receptors in the psychotomimetic actions of phencyclidine". Int. J. Neuropsychopharmacol. 3 (4): 333–338. doi: 10.1017/S1461145700002091 . PMID   11343613.
  45. 1 2 3 4 Goodman CB, Thomas DN, Pert A, Emilien B, Cadet JL, Carroll FI, et al. (1994). "RTI-4793-14, a new ligand with high affinity and selectivity for the (+)-MK801-insensitive [3H]1-]1-(2-thienyl)cyclohexyl]piperidine binding site (PCP site 2) of guinea pig brain". Synapse. 16 (1): 59–65. doi:10.1002/syn.890160107. PMID   8134901. S2CID   19829696.
  46. ↑ Large CH, Bison S, Sartori I, Read KD, Gozzi A, Quarta D, et al. (Jul 2011). "The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia". The Journal of Pharmacology and Experimental Therapeutics. 338 (1): 100–13. doi:10.1124/jpet.110.178475. PMID   21487071. S2CID   1862326.
  47. ↑ Anis NA, Berry SC, Burton NR, D. Lodge (1983). "The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate". British Journal of Pharmacology . 79 (2): 565–575. doi:10.1111/j.1476-5381.1983.tb11031.x. PMC   2044888 . PMID   6317114.
  48. 1 2 3 4 Morris H, Wallach J (2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs". Drug Testing and Analysis. 6 (7–8): 614–32. doi:10.1002/dta.1620. PMID   24678061.
  49. ↑ Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK (Apr 2014). "Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy". Therapeutic Advances in Psychopharmacology. 4 (2): 75–99. doi:10.1177/2045125313507739. PMC   3952483 . PMID   24688759.
  50. ↑ Klockgether T, Turski L, Schwarz M, Sontag KH, Lehmann J (Oct 1988). "Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine". Brain Research. 461 (2): 343–8. doi:10.1016/0006-8993(88)90265-X. PMID   2846121. S2CID   41671395.
  51. ↑ Burns JM, Boyer EW (2013). "Antitussives and substance abuse". Substance Abuse and Rehabilitation. 4: 75–82. doi: 10.2147/SAR.S36761 . PMC   3931656 . PMID   24648790.
  52. ↑ Aguayo LG, Warnick JE, Maayani S, Glick SD, Weinstein H, Albuquerque EX (May 1982). "Site of action of phencyclidine. IV. Interaction of phencyclidine and its analogues on ionic channels of the electrically excitable membrane and nicotinic receptor: implications for behavioral effects". Molecular Pharmacology. 21 (3): 637–47. PMID   6287200.
  53. ↑ Zarantonello P, Bettini E, Paio A, Simoncelli C, Terreni S, Cardullo F (Apr 2011). "Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists". Bioorganic & Medicinal Chemistry Letters. 21 (7): 2059–63. doi:10.1016/j.bmcl.2011.02.009. PMID   21334205.
  54. ↑ Lin H, Vicini S, Hsu FC, Doshi S, Takano H, Coulter DA, et al. (Sep 2010). "Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons". Proceedings of the National Academy of Sciences of the United States of America. 107 (38): 16661–6. Bibcode:2010PNAS..10716661L. doi: 10.1073/pnas.1007397107 . PMC   2944730 . PMID   20817852.
  55. ↑ Fisher JL, Dani JA (Oct 2000). "Nicotinic receptors on hippocampal cultures can increase synaptic glutamate currents while decreasing the NMDA-receptor component". Neuropharmacology. 39 (13): 2756–69. doi:10.1016/s0028-3908(00)00102-7. PMID   11044745. S2CID   42066117.
  56. ↑ Prestori F, Bonardi C, Mapelli L, Lombardo P, Goselink R, De Stefano ME, et al. (2013). "Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage". PLOS ONE. 8 (5): e64828. Bibcode:2013PLoSO...864828P. doi: 10.1371/journal.pone.0064828 . PMC   3669396 . PMID   23741401.
  57. ↑ Seeman P, Ko F, Tallerico T (Sep 2005). "Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics". Molecular Psychiatry. 10 (9): 877–83. doi: 10.1038/sj.mp.4001682 . PMID   15852061.
  58. ↑ Giannini AJ, Nageotte C, Loiselle RH, Malone DA, Price WA (1984). "Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity". Journal of Toxicology. Clinical Toxicology. 22 (6): 573–9. doi:10.3109/15563658408992586. PMID   6535849.
  59. ↑ Rothman RB, Reid AA, Monn JA, Jacobson AE, Rice KC (Dec 1989). "The psychotomimetic drug phencyclidine labels two high affinity binding sites in guinea pig brain: evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrier-associated phencyclidine binding sites". Molecular Pharmacology. 36 (6): 887–96. PMID   2557536.
  60. ↑ Castellani S, Giannini AJ, Adams PM (1982). "Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat". Psychopharmacology. 78 (1): 76–80. doi:10.1007/BF00470593. PMID   6815700. S2CID   21996319.
  61. ↑ "Phencyclidine". www.drugbank.ca. Retrieved 28 January 2019.
  62. ↑ Martin D, Lodge D (October 1988). "Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours". Pharmacology, Biochemistry, and Behavior. 31 (2): 279–286. doi:10.1016/0091-3057(88)90346-2. PMID   2854262. S2CID   12247783.
  63. 1 2 Kohrs R, Durieux ME (November 1998). "Ketamine: teaching an old drug new tricks". Anesthesia and Analgesia. 87 (5): 1186–1193. doi: 10.1097/00000539-199811000-00039 . PMID   9806706.
  64. ↑ Kroemer RT, Koutsilieri E, Hecht P, Liedl KR, Riederer P, Kornhuber J (January 1998). "Quantitative analysis of the structural requirements for blockade of the N-methyl-D-aspartate receptor at the phencyclidine binding site". Journal of Medicinal Chemistry. 41 (3): 393–400. doi:10.1021/jm9704412. PMID   9464369.
  65. ↑ Nadler V, Kloog Y, Sokolovsky M (March 1990). "Distinctive structural requirement for the binding of uncompetitive blockers (phencyclidine-like drugs) to the NMDA receptor". European Journal of Pharmacology. 188 (2–3): 97–104. doi:10.1016/0922-4106(90)90044-X. PMID   2156715.
  66. ↑ Olney JW, Labruyere J, Price MT (June 1989). "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs". Science. 244 (4910): 1360–1362. Bibcode:1989Sci...244.1360O. doi:10.1126/science.2660263. PMID   2660263.
  67. ↑ Hargreaves RJ, Hill RG, Iversen LL (1994). "Neuroprotective NMDA Antagonists: The Controversy over Their Potential for Adverse Effects on Cortical Neuronal Morphology". Brain Edema IX. Acta Neurochirurgica. Supplementum. Vol. 60. pp. 15–19. doi:10.1007/978-3-7091-9334-1_4. ISBN   978-3-7091-9336-5. PMID   7976530.
  68. ↑ Jansen, Karl. Ketamine: Dreams and Realities. MAPS, 2004. ISBN   0-9660019-7-4
  69. ↑ Reynolds LM, Cochran SM, Morris BJ, Pratt JA, Reynolds GP (March 2005). "Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain". Schizophrenia Research. 73 (2–3): 147–152. doi:10.1016/j.schres.2004.02.003. PMID   15653257. S2CID   1651693.
  70. ↑ Murray JB (May 2002). "Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research". The Journal of Psychology. 136 (3): 319–327. doi:10.1080/00223980209604159. PMID   12206280. S2CID   20334137.
  71. 1 2 Lodge D, Mercier MS (September 2015). "Ketamine and phencyclidine: the good, the bad and the unexpected". British Journal of Pharmacology. 172 (17): 4254–4276. doi:10.1111/bph.13222. PMC   4556466 . PMID   26075331.
  72. ↑ Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D (September 2012). "Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia". Schizophrenia Bulletin. 38 (5): 958–966. doi:10.1093/schbul/sbs069. PMC   3446214 . PMID   22987851.
  73. ↑ Itzhak Y, Kalir A, Weissman BA, Cohen S (May 1981). "New analgesic drugs derived from phencyclidine". Journal of Medicinal Chemistry. 24 (5): 496–9. doi:10.1021/jm00137a004. PMID   7241506.
  74. ↑ Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R (Mar 1989). "Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs". Pharmacology Biochemistry and Behavior. 32 (3): 699–705. doi:10.1016/0091-3057(89)90020-8. PMID   2544905. S2CID   7672918.
  75. 1 2 Kötz A, Merkel P (May 1926). "Zur Kenntnis hydroaromatischer Alkamine". Journal für Praktische Chemie (in German). 113 (1): 49–76. doi:10.1002/prac.19261130107. ISSN   0021-8383.
  76. ↑ Bunney Jr WE, Hippius H, Laakmann G, Schmauß M (2012). Neuropsychopharmacology: Proceedings of the XVIth C.I.N.P. Congress, Munich, August, 15-19, 1988. Springer Science & Business Media. p. 717. ISBN   978-3-642-74034-3 – via Google Books.
  77. ↑ Lindgren JE, Holmstedt B (1983). "Guide to the Analysis of Phencyclidine and its Metabolites in Biological Material". Toxicology in the Use, Misuse, and Abuse of Food, Drugs, and Chemicals. Archives of Toxicology. Vol. 6. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 61–73. doi:10.1007/978-3-642-69083-9_10. ISBN   978-3-540-12392-7. ISSN   0171-9750. PMID   6578750.
  78. 1 2 Tasman A, Kay J, Lieberman JA, First MB, Riba M (2015). Psychiatry, 2 Volume Set. John Wiley & Sons. p. 4943. ISBN   978-1-118-75336-1 – via Google Books.
  79. ↑ "Controlled Substances" (PDF). deadiversion.usdoj.gov. US: Drug Enforcement Administration. March 12, 2014. Archived (PDF) from the original on 2014-04-17. Retrieved June 15, 2014.
  80. ↑ "Established Aggregate Production Quotas for Schedule I and II Controlled Substances and Established Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2014". deadiversion.usdoj.gov. US: Drug Enforcement Administration. August 30, 2013. Archived from the original on 2014-04-17. Retrieved June 15, 2014.
  81. ↑ "The Misuse of Drugs Act 1971 (Modification) Order 1979". legislation.gov.uk. Retrieved 2016-01-31.
  82. ↑ Nag A (April 11, 2013). "Christie's Evening Auction to present a major painting by Jean-Michel Basquiat". The Economic Times. Retrieved 2020-09-26.
  83. ↑ "New City Hunter Anime Film's Trailer Unveils More Cast, Theme Songs, September 8 Debut". Anime News Network. 2024-06-28. Retrieved 2024-06-28.
  84. ↑ "Prime Video Debuts Teaser of an Original Song and Announces Main Cast for Hazbin Hotel at New York Comic Con". press.amazonstudios.com (Press release). Amazon Studios. Retrieved 2024-02-22.
  85. ↑ HAZBIN HOTEL Charity Sketch Request Stream Ft. Vivziepop, Cherri Bomb, and Angel Dust! . Retrieved 2024-02-22– via YouTube.
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