Editing Phencyclidine (section)

==Pharmacology==

===Pharmacodynamics===
{| class="wikitable floatright" style="font-size:small;"
|+ Phencyclidine<ref name="PDSP">{{cite web |title=PDSP K<sub>i</sub> Database |work=Psychoactive Drug Screening Program (PDSP) |vauthors=Roth BL, Driscol J|author1-link=Bryan Roth |publisher=University of North Carolina at Chapel Hill and the United States National Institute of Mental Health |access-date=14 August 2017 |url=https://kidbdev.med.unc.edu/databases/pdsp.php?knowID=0&kiKey=&receptorDD=&receptor=&speciesDD=&species=&sourcesDD=&source=&hotLigandDD=&hotLigand=&testLigandDD=&testFreeRadio=testFreeRadio&testLigand=phencyclidine&referenceDD=&reference=&KiGreater=&KiLess=&kiAllRadio=all&doQuery=Submit+Query}}</ref><ref name="pmid29953199">{{cite journal |vauthors=Berton JL, Seto M, Lindsley CW |title=DARK Classics in Chemical Neuroscience: Phencyclidine (PCP) |journal=ACS Chem Neurosci |volume=9| issue=10| pages=2459–2474| date=June 2018 |pmid=29953199 |doi=10.1021/acschemneuro.8b00266 |s2cid=49603581}}</ref>
|-
! Site !! K<sub>i</sub> ([[Nanomolar|nM]]) !! Action !! Species !! Ref
|-
| '''{{abbrlink|NMDA|N-Methyl-D-aspartate receptor}}''' || '''59'''|| '''Antagonist''' || '''Human''' || <ref name="pmid23527166">{{cite journal | vauthors = Roth BL, Gibbons S, Arunotayanun W, Huang XP, Setola V, Treble R, Iversen L | title = The ketamine analogue methoxetamine and 3- and 4-methoxy analogues of phencyclidine are high affinity and selective ligands for the glutamate NMDA receptor | journal = PLOS ONE | volume = 8 | issue = 3 | pages = e59334 | year = 2013 | pmid = 23527166 | pmc = 3602154 | doi = 10.1371/journal.pone.0059334 | bibcode = 2013PLoSO...859334R | doi-access = free }}</ref><ref name="pmid7968938" />
|-
| {{abbrlink|MOR|μ-Opioid receptor}} || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|-
| {{abbrlink|DOR|δ-Opioid receptor}} || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|-
| {{abbrlink|KOR|κ-Opioid receptor}} || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|-
| {{abbrlink|NOP|Nociceptin receptor}} || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|-
| [[Sigma-1 receptor|σ<sub>1</sub>]] || >10,000 || Agonist || Guinea pig || <ref name="pmid23527166" /><ref name="pmid24257811">{{cite journal | vauthors = Frohlich J, Van Horn JD | title = Reviewing the ketamine model for schizophrenia | journal = J. Psychopharmacol. (Oxford) | volume = 28 | issue = 4 | pages = 287–302 | year = 2014 | pmid = 24257811 | pmc = 4133098 | doi = 10.1177/0269881113512909 }}</ref>
|-
| '''[[Sigma-2 receptor|σ<sub>2</sub>]]''' || '''136''' || '''Agonist''' || '''Rat''' || <ref name="pmid23527166" />
|-
| [[D2 receptor|D<sub>2</sub>]] || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|-
| &nbsp;&nbsp;'''[[D2 receptor#Active (D2HighR) and inactive (D2LowR) forms|D<sub>2</sub><sup>High</sup>]]''' || '''2.7–4.3'''<br />'''144 ([[EC50|EC<sub>50</sub>]])''' || '''Partial Agonist''' || '''Rat/human'''<br />'''Human''' || <ref name="pmid18720422">{{cite journal | vauthors = Seeman P, Guan HC | title = Phencyclidine and glutamate agonist LY379268 stimulate dopamine D2High receptors: D2 basis for schizophrenia | journal = Synapse | volume = 62 | issue = 11 | pages = 819–28 | year = 2008 | pmid = 18720422 | doi = 10.1002/syn.20561 | s2cid = 206519749 }}</ref><ref name="pmid12232776">{{cite journal | vauthors = Kapur S, Seeman P | title = 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 | journal = Mol. Psychiatry | volume = 7 | issue = 8 | pages = 837–44 | year = 2002 | pmid = 12232776 | doi = 10.1038/sj.mp.4001093 | doi-access = free }}</ref><br /><ref name="pmid19391150">{{cite journal | vauthors = Seeman P, Guan HC, Hirbec H | title = Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil | journal = Synapse | volume = 63 | issue = 8 | pages = 698–704 | year = 2009 | pmid = 19391150 | doi = 10.1002/syn.20647 | s2cid = 17758902 }}</ref>
|-
| [[5-HT2A receptor|5-HT<sub>2A</sub>]] || >10,000 || {{abbr|ND|No data}} || Human || <ref name="pmid23527166" />
|- 
| &nbsp;&nbsp;[[5-HT2A receptor|5-HT<sub>2A</sub><sup>High</sup>]] || ≥5,000 || Partial
Agonist
| Rat || <ref name="pmid12232776" /><ref name="pmid11343613">{{cite journal | vauthors = Rabin RA, Doat M, Winter JC | title = Role of serotonergic 5-HT2A receptors in the psychotomimetic actions of phencyclidine | journal = Int. J. Neuropsychopharmacol. | volume = 3 | issue = 4 | pages = 333–338 | year = 2000 | pmid = 11343613 | doi = 10.1017/S1461145700002091 | doi-access = free }}</ref>
|-
| {{abbrlink|SERT|Serotonin transporter}} || 2,234 || Inhibitor || Human || <ref name="pmid23527166" />
|-
| {{abbrlink|NET|Norepinephrine transporter}} || >10,000 || Inhibitor || Human || <ref name="pmid23527166" />
|-
| {{abbrlink|DAT|Dopamine transporter}} || >10,000 || Inhibitor || Human || <ref name="pmid23527166" />
|-
| '''[[Phencyclidine site 2|{{abbr|PCP|Phencyclidine}}<sub>2</sub>]]''' || '''154''' || agonist || '''Human''' || <ref name="pmid7968938">{{cite journal | vauthors = Rothman RB | title = PCP site 2: a high affinity MK-801-insensitive phencyclidine binding site | journal = Neurotoxicol Teratol | volume = 16 | issue = 4 | pages = 343–53 | year = 1994 | pmid = 7968938 | doi = 10.1016/0892-0362(94)90022-1| bibcode = 1994NTxT...16..343R | url = https://zenodo.org/record/1258623}}</ref>
|-
| [[Serotonin reuptake inhibitor|[<sup>3</sup>H]{{abbr|5-HT|Serotonin}} uptake]] || 1,424 ([[IC50|IC<sub>50</sub>]]) || Inhibitor || Rat || <ref name="pmid8134901">{{cite journal | vauthors = Goodman CB, Thomas DN, Pert A, Emilien B, Cadet JL, Carroll FI, Blough BE, Mascarella SW, Rogawski MA, Subramaniam S | title = 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 | journal = Synapse | volume = 16 | issue = 1 | pages = 59–65 | year = 1994 | pmid = 8134901 | doi = 10.1002/syn.890160107 | s2cid = 19829696 | url = https://zenodo.org/record/1229378}}</ref>
|-
| [[Norepinephrine reuptake inhibitor|[<sup>3</sup>H]{{abbr|NIS|Nisoxetine}} binding]] || 16,628 (IC<sub>50</sub>) || Inhibitor || Rat || <ref name="pmid8134901" />
|-
| '''[[Dopamine reuptake inhibitor|[<sup>3</sup>H]{{abbr|DA|Dopamine}} uptake]]''' || '''347 (IC<sub>50</sub>)''' || '''Inhibitor''' || '''Rat''' || <ref name="pmid8134901" />
|-
| [[Dopamine reuptake inhibitor|[<sup>3</sup>H]{{abbr|CFT|WIN-35428}} binding]] || 1,547 (IC<sub>50</sub>) || Inhibitor || Rat || <ref name="pmid8134901" />
|- class="sortbottom"
| colspan="5" style="width: 1px;" | Values are K<sub>i</sub> (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]].<ref>{{cite journal | vauthors = Large CH, Bison S, Sartori I, Read KD, Gozzi A, Quarta D, Antolini M, Hollands E, Gill CH, Gunthorpe MJ, Idris N, Neill JC, Alvaro GS | title = The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 338 | issue = 1 | pages = 100–113 | date = July 2011 | pmid = 21487071 | doi = 10.1124/jpet.110.178475 | s2cid = 1862326 }}</ref><ref name="pmid19391150" /> 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 (neuroscientist)|David Lodge]]<ref>{{Cite journal |vauthors = Anis NA, Berry SC, Burton NR, (([[David Lodge (neuroscientist)|D. Lodge]])) | title = The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate | journal = [[British Journal of Pharmacology]] | volume = 79 | issue = 2 | pages = 565–575 | year = 1983 | pmc = 2044888 | pmid = 6317114 | doi=10.1111/j.1476-5381.1983.tb11031.x}}</ref> and colleagues.<ref name="Morris2014">{{cite journal|vauthors=Morris H, Wallach J|year=2014|title=From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs|journal=Drug Testing and Analysis|volume=6|issue=7–8|pages=614–632|doi=10.1002/dta.1620|pmid=24678061}}</ref> Other NMDA receptor antagonists include [[ketamine]],<ref name=Caddy2010>{{cite journal | vauthors = Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK | title = Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy | journal = Therapeutic Advances in Psychopharmacology | volume = 4 | issue = 2 | pages = 75–99 | date = April 2014 | pmid = 24688759 | doi = 10.1177/2045125313507739 | pmc=3952483}}</ref> [[tiletamine]],<ref>{{cite journal | vauthors = Klockgether T, Turski L, Schwarz M, Sontag KH, Lehmann J | title = Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine | journal = Brain Research | volume = 461 | issue = 2 | pages = 343–8 | date = Oct 1988 | pmid = 2846121 | doi = 10.1016/0006-8993(88)90265-X | s2cid = 41671395 }}</ref> [[dextromethorphan]],<ref name=Burns>{{cite journal | vauthors = Burns JM, Boyer EW | title = Antitussives and substance abuse | journal = Substance Abuse and Rehabilitation | volume = 4 | pages = 75–82 | year = 2013 | pmid = 24648790 | pmc = 3931656 | doi = 10.2147/SAR.S36761 | doi-access = free }}</ref> [[nitrous oxide]], and [[dizocilpine]] (MK-801).

Research also indicates that PCP inhibits [[nicotinic acetylcholine receptor]]s (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors<ref>{{cite journal | vauthors = Aguayo LG, Warnick JE, Maayani S, Glick SD, Weinstein H, Albuquerque EX | title = 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 | journal = Molecular Pharmacology | volume = 21 | issue = 3 | pages = 637–647 | date = May 1982 | pmid = 6287200 }}</ref> and NMDA receptors.<ref>{{cite journal | vauthors = Zarantonello P, Bettini E, Paio A, Simoncelli C, Terreni S, Cardullo F | title = Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 21 | issue = 7 | pages = 2059–63 | date = Apr 2011 | pmid = 21334205 | doi = 10.1016/j.bmcl.2011.02.009 }}</ref> 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.<ref>{{cite journal | vauthors = Lin H, Vicini S, Hsu FC, Doshi S, Takano H, Coulter DA, Lynch DR | title = Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 38 | pages = 16661–6 | date = Sep 2010 | pmid = 20817852 | pmc = 2944730 | doi = 10.1073/pnas.1007397107 | bibcode = 2010PNAS..10716661L | doi-access = free }}</ref> These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the [[hippocampus]]<ref>{{cite journal | vauthors = Fisher JL, Dani JA | title = Nicotinic receptors on hippocampal cultures can increase synaptic glutamate currents while decreasing the NMDA-receptor component | journal = Neuropharmacology | volume = 39 | issue = 13 | pages = 2756–69 | date = Oct 2000 | pmid = 11044745 | doi = 10.1016/s0028-3908(00)00102-7 | s2cid = 42066117 }}</ref> and [[cerebellum]]<ref>{{cite journal | vauthors = Prestori F, Bonardi C, Mapelli L, Lombardo P, Goselink R, De Stefano ME, Gandolfi D, Mapelli J, Bertrand D, Schonewille M, De Zeeuw C, D'Angelo E | title = Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e64828 | year = 2013 | pmid = 23741401 | pmc = 3669396 | doi = 10.1371/journal.pone.0064828 | bibcode = 2013PLoSO...864828P | doi-access = free }}</ref> 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.<ref name=NIH2016Hal/>

PCP, like ketamine, also acts as a potent [[dopamine]] [[D2 receptor|D<sub>2</sub><sup>High</sup> receptor]] [[partial agonist]] in rat brain homogenate<ref name="pmid19391150" /> and has affinity for the human cloned D<sub>2</sub><sup>High</sup> receptor.<ref name="D2 in ketamine and pcp">{{cite journal | vauthors = Seeman P, Ko F, Tallerico T | title = Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics | journal = Molecular Psychiatry | volume = 10 | issue = 9 | pages = 877–883 | date = September 2005 | pmid = 15852061 | doi = 10.1038/sj.mp.4001682 | doi-access = free }}</ref> This activity may be associated with some of the other more psychotic features of PCP intoxication, which is evidenced by the successful use of D<sub>2</sub> receptor antagonists (such as [[haloperidol]]) in the treatment of PCP psychosis.<ref>{{cite journal | vauthors = Giannini AJ, Nageotte C, Loiselle RH, Malone DA, Price WA | title = Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity | journal = Journal of Toxicology. Clinical Toxicology | volume = 22 | issue = 6 | pages = 573–9 | year = 1984 | pmid = 6535849 | doi = 10.3109/15563658408992586 }}</ref>

In addition to its well-explored interactions with NMDA receptors, PCP has also been shown to [[dopamine reuptake inhibitor|inhibit dopamine reuptake]], and thereby leads to increased extracellular levels of dopamine and hence increased [[dopaminergic]] [[neurotransmission]].<ref>{{cite journal | vauthors = Rothman RB, Reid AA, Monn JA, Jacobson AE, Rice KC | title = 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 | journal = Molecular Pharmacology | volume = 36 | issue = 6 | pages = 887–896 | date = December 1989 | pmid = 2557536 }}</ref> However, PCP has little [[affinity (pharmacology)|affinity]] for the human [[monoamine transporter]]s, including the [[dopamine transporter]] (DAT).<ref name="pmid23527166" /> Instead, its [[monoamine reuptake inhibitor|inhibition of monoamine reuptake]] may be mediated by interactions with [[regulatory site|allosteric site]]s on the monoamine transporters.<ref name="pmid23527166" /> PCP is notably a high-affinity [[ligand (biochemistry)|ligand]] of the [[PCP site 2]] (K<sub>i</sub> = 154&nbsp;nM), a not-well-characterized site associated with monoamine reuptake inhibition.<ref name="pmid7968938" />

Studies on rats indicate that PCP interacts indirectly with [[opioid receptor]]s ([[endorphin]] and [[enkephalin]]) to produce analgesia.<ref>{{cite journal | vauthors = Castellani S, Giannini AJ, Adams PM | title = Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat | journal = Psychopharmacology | volume = 78 | issue = 1 | pages = 76–80 | year = 1982 | pmid = 6815700 | doi = 10.1007/BF00470593 | s2cid = 21996319 }}</ref>

A binding study assessed PCP at 56&nbsp;sites including [[neurotransmitter receptor]]s and [[neurotransmitter transporter|transporter]]s and found that PCP had K<sub>i</sub> values of >10,000&nbsp;nM at all sites except the [[dizocilpine]] (MK-801) site of the NMDA receptor (K<sub>i</sub> = 59&nbsp;nM), the [[sigma-2 receptor|σ<sub>2</sub> receptor]] ([[PC12 cell line|PC12]]) (K<sub>i</sub> = 136&nbsp;nM), and the [[serotonin transporter]] (K<sub>i</sub> = 2,234&nbsp;nM).<ref name="pmid23527166" /> The study notably found K<sub>i</sub> values of >10,000&nbsp;nM for the [[D2 receptor|D<sub>2</sub> receptor]], the [[opioid receptor]]s, the [[sigma-1 receptor|σ<sub>1</sub> receptor]], and the [[dopamine transporter|dopamine]] and [[norepinephrine transporter]]s.<ref name="pmid23527166" /> These results suggest that PCP is a highly selective ligand of the NMDAR and σ<sub>2</sub> receptor.<ref name="pmid23527166" /> However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake.<ref name="pmid23527166" />

===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.<ref name=drugbank>{{cite web |title=Phencyclidine |url=https://www.drugbank.ca/drugs/DB03575 |website=www.drugbank.ca |access-date=28 January 2019}}</ref><ref name=beyT>{{cite journal | vauthors = Bey T, Patel A | title = Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug | journal = The California Journal of Emergency Medicine | volume = 8 | issue = 1 | pages = 9–14 | date = February 2007 | pmid = 20440387 | pmc = 2859735 }}</ref> 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.<ref>{{cite journal | vauthors = Martin D, Lodge D | title = Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours | journal = Pharmacology, Biochemistry, and Behavior | volume = 31 | issue = 2 | pages = 279–286 | date = October 1988 | pmid = 2854262 | doi = 10.1016/0091-3057(88)90346-2 | s2cid = 12247783 }}</ref> The PCP binding site is within close proximity to the magnesium blocking site, which may explain the similar inhibitory effects.<ref name="Kohrs_1998">{{cite journal | vauthors = Kohrs R, Durieux ME | title = Ketamine: teaching an old drug new tricks | journal = Anesthesia and Analgesia | volume = 87 | issue = 5 | pages = 1186–1193 | date = November 1998 | pmid = 9806706 | doi = 10.1097/00000539-199811000-00039 | doi-access = free }}</ref> Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction.<ref>{{cite journal | vauthors = Kroemer RT, Koutsilieri E, Hecht P, Liedl KR, Riederer P, Kornhuber J | title = Quantitative analysis of the structural requirements for blockade of the N-methyl-D-aspartate receptor at the phencyclidine binding site | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 3 | pages = 393–400 | date = January 1998 | pmid = 9464369 | doi = 10.1021/jm9704412 }}</ref> 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.<ref>{{cite journal | vauthors = Nadler V, Kloog Y, Sokolovsky M | title = Distinctive structural requirement for the binding of uncompetitive blockers (phencyclidine-like drugs) to the NMDA receptor | journal = European Journal of Pharmacology | volume = 188 | issue = 2–3 | pages = 97–104 | date = March 1990 | pmid = 2156715 | doi = 10.1016/0922-4106(90)90044-X }}</ref>

====Neurotoxicity====
Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of [[brain damage]] called [[Olney's lesions]] in rats.<ref>{{cite journal |vauthors=Olney JW, Labruyere J, Price MT |title=Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs |journal=Science |volume=244 |issue=4910 |pages=1360–1362 |date=June 1989 |pmid=2660263 |doi=10.1126/science.2660263 |bibcode=1989Sci...244.1360O}}</ref><ref>{{cite book |vauthors=Hargreaves RJ, Hill RG, Iversen LL |chapter=Neuroprotective NMDA Antagonists: The Controversy over Their Potential for Adverse Effects on Cortical Neuronal Morphology |title=Brain Edema IX |series=Acta Neurochirurgica. Supplementum |volume=60 |pages=15–19 |year=1994 |pmid=7976530 |isbn=978-3-7091-9336-5 |doi=10.1007/978-3-7091-9334-1_4}}</ref> Studies conducted on rats showed that high doses of the NMDA receptor antagonist [[dizocilpine]] caused reversible [[vacuole]]s 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,<ref>Jansen, Karl. ''Ketamine: Dreams and Realities''. MAPS, 2004. {{ISBN|0-9660019-7-4}}</ref> 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.<ref name=psychotic_PCP_rats>{{cite journal |vauthors=Reynolds LM, Cochran SM, Morris BJ, Pratt JA, Reynolds GP |title=Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain |journal=Schizophrenia Research |volume=73 |issue=2–3 |pages=147–152 |date=March 2005 |pmid=15653257 |doi=10.1016/j.schres.2004.02.003 |s2cid=1651693}}</ref> It also induces symptoms in humans that mimic schizophrenia.<ref>{{cite journal |vauthors=Murray JB |title=Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research |journal=The Journal of Psychology |volume=136 |issue=3 |pages=319–327 |date=May 2002 |pmid=12206280 |doi=10.1080/00223980209604159 |s2cid=20334137}}</ref> 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.<ref name="Lodge_2015">{{cite journal |vauthors=Lodge D, Mercier MS |title=Ketamine and phencyclidine: the good, the bad and the unexpected |journal=British Journal of Pharmacology |volume=172 |issue=17 |pages=4254–4276 |date=September 2015 |pmid=26075331 |pmc=4556466 |doi=10.1111/bph.13222}}</ref> PCP-induced augmentation of dopamine release may link the NMDA and [[dopamine hypothesis of schizophrenia|dopamine]] hypotheses of schizophrenia.<ref>{{cite journal |vauthors=Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D |title=Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia |journal=Schizophrenia Bulletin |volume=38 |issue=5 |pages=958–966 |date=September 2012 |pmid=22987851 |pmc=3446214 |doi=10.1093/schbul/sbs069}}</ref>

===Pharmacokinetics===
[[File:PCP2PCandPOPERIDINE.png|class=skin-invert-image|thumb|Conversion of PCP into PC and piperidine by heat.]]
PCP is both water- and lipid-soluble and is therefore distributed throughout the body quickly.<ref name="Kohrs_1998" /> PCP is metabolized into [[PCHP]], [[4-Phenyl-4-(1-piperidinyl)cyclohexanol|PPC]] and [[PCAA]]. The drug is metabolized 90% by [[oxidation|oxidative]] [[hydroxylation]] in the [[liver]] during the [[first-pass effect|first pass]]. [[Metabolite]]s are [[glucuronidated]] and [[excretion|excreted]] in the [[urine]]. Nine percent of ingested PCP is excreted in its unchanged form.<ref name=beyT />

When smoked, some of the compound is broken down by heat into [[1-phenyl-1-cyclohexene|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.<ref name=beyT />