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3-HO-PCP
Clinical data
Other names	3-Hydroxyphencyclidine; 3-OH-PCP; PCP-3-OH
Legal status
Legal status	CA: Schedule I; DE: NpSG (Industrial and scientific use only); UK: Class B; Illegal in Sweden and Switzerland;
Identifiers
	IUPAC name 3-[1-(Piperidin-1-yl)cyclohexyl]phenol;
CAS Number	79787-43-2 ; 79295-51-5 (hydrochloride);
PubChem CID	133277;
ChemSpider	117583;
UNII	V886QLHNA6;
CompTox Dashboard (EPA)	DTXSID20229918 ;
Chemical and physical data
Formula	C17H25NO
Molar mass	259.393 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES c1cc(cc(c1)O)C2(CCCCC2)N3CCCCC3;
	InChI InChI=1S/C17H25NO/c19-16-9-7-8-15(14-16)17(10-3-1-4-11-17)18-12-5-2-6-13-18/h7-9,14,19H,1-6,10-13H2; Key:AMSXTZUCNOKUEN-UHFFFAOYSA-N;

3-Hydroxyphencyclidine (3-HO-PCP) is a dissociative of the arylcyclohexylamine class related to phencyclidine (PCP) that has been sold online as a designer drug.^[1]^[2]

Pharmacology

3-HO-PCP acts as a high-affinity uncompetitive antagonist of the NMDA receptor via the dizocilpine (MK-801) site (K_i = 30 nM).^[1]^[3] It has much higher affinity than PCP for this site (K_i = 250 nM, for comparison; 8-fold difference).^[3] The drug also has high affinity for the μ-opioid receptor (MOR) (K_i = 39–60 nM) in animal test subjects,^[1]^[3]^[4]^[5] the κ-opioid receptor (KOR) (K_i = 140 nM),^[4] and the sigma σ₁ receptor (K_i = 42 nM; IC₅₀ = 19 nM),^[4]^[6]^[7]^[8] whereas it has only low affinity for the δ-opioid receptor (K_i = 2,300 nM).^[4] The high affinity of 3-HO-PCP for opioid receptors is unique among arylcyclohexylamines and is in contrast to PCP, which has only very low affinity for the MOR (K_i = 11,000–26,000 nM; 282- to 433-fold difference) and the other opioid receptors (K_i = 4,100 nM for the KOR and 73,000 nM for the DOR).^[3]^[4]

Although it was hypothesized that 3-HO-PCP might be a metabolite of PCP in humans, there is no evidence that this is the case.^[9]^[10] 3-HO-PCP is a metabolite of 3-MeO-PCP.^[11]

Chemistry

3-HO-PCP is an arylcyclohexylamine.^[1] Close analogues of 3-HO-PCP include PCP, 3-MeO-PCP, 4-MeO-PCP, 3-MeO-PCMo, and somewhat more distantly ketamine, methoxyketamine, 3-MeO-PCE, methoxetamine and dimetamine.^[1]

History

3-HO-PCP was mentioned by a chemist under the pseudonym "John Q. Beagle" in 1999 in a post on The Hive.^[1] The psychoactive effects of 3-HO-PCP have been described by Bluelight users even before its availability as a research chemical in 2009.^[1]

Society and culture

Legal status

On October 18, 2012, the Advisory Council on the Misuse of Drugs in the United Kingdom released a report about methoxetamine, saying that the "harms of methoxetamine are commensurate with Class B of the Misuse of Drugs Act (1971)", despite the fact that the act does not classify drugs based on harm. The report went on to suggest that all analogues of MXE should also become class B drugs and suggested a catch-all clause covering both existing and unresearched arylcyclohexamines, including 3-HO-PCP.^[12]

3-HO-PCP is banned in Sweden^[13]^[14] and Switzerland.^[15]

References

^ ^a ^b ^c ^d ^e ^f ^g 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): 614–632. doi:10.1002/dta.1620. PMID 24678061.
^ Davidsen AB, Mardal M, Johansen SS, Dalsgaard PW, Linnet K (July 2020). "In vitro and in vivo metabolism and detection of 3-HO-PCP, a synthetic phencyclidine, in human samples and pooled human hepatocytes using high resolution mass spectrometry". Drug Testing and Analysis. 12 (7): 987–993. doi:10.1002/dta.2807. PMID 32311838. S2CID 216047397.
^ ^a ^b ^c ^d Kamenka JM, Chiche B, Goudal R, Geneste P, Vignon J, Vincent JP, Lazdunski M (April 1982). "Chemical synthesis and molecular pharmacology of hydroxylated 1-(1-phenylcyclohexyl-piperidine derivatives". Journal of Medicinal Chemistry. 25 (4): 431–435. doi:10.1021/jm00346a019. PMID 6279847.
^ ^a ^b ^c ^d ^e Johnson N, Itzhak Y, Pasternak GW (June 1984). "Interaction of two phencyclidine opiate-like derivatives with 3H-opioid binding sites". European Journal of Pharmacology. 101 (3–4): 281–284. doi:10.1016/0014-2999(84)90171-7. PMID 6088255.
^ Itzhak Y, Kalir A, Sarne Y (July 1981). "On the opioid nature of phencyclidine and its 3-hydroxy derivative". European Journal of Pharmacology. 73 (2–3): 229–233. doi:10.1016/0014-2999(81)90097-2. PMID 6273187.
^ Itzhak Y, Hiller JM, Simon EJ (January 1985). "Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes". Molecular Pharmacology. 27 (1): 46–52. PMID 3965930.
^ Itzhak Y (April 1987). "[3H]PCP-3-OH and (+)[3H]SKF 10047 binding sites in rat brain membranes: evidence of multiplicity". European Journal of Pharmacology. 136 (2): 231–234. doi:10.1016/0014-2999(87)90715-1. PMID 3036548.
^ Itzhak Y (1988). "Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites". Life Sciences. 42 (7): 745–752. doi:10.1016/0024-3205(88)90646-7. PMID 2893238.
^ Holsztynska EJ, Domino EF (1985). "Biotransformation of phencyclidine". Drug Metabolism Reviews. 16 (3): 285–320. doi:10.3109/03602538508991437. PMID 3914938.
^ Holsztynska EJ, Domino EF (1986). "Quantitation of phencyclidine, its metabolites, and derivatives by gas chromatography with nitrogen-phosphorus detection: application for in vivo and in vitro biotransformation studies". Journal of Analytical Toxicology. 10 (3): 107–115. doi:10.1093/jat/10.3.107. PMID 3724069.
^ Wallach J, Brandt SD (2018). Maurer HH, Brandt SD (eds.). "Phencyclidine-Based New Psychoactive Substances". Handbook of Experimental Pharmacology. 252. Cham: Springer International Publishing=: 261–303. doi:10.1007/164_2018_124. ISBN 978-3-030-10561-7. PMID 30105474.
^ "(ACMD) Methoxetamine Report (2012)" (PDF). UK Home Office. 2012-10-18. p. 14. Retrieved 2015-06-24.
^ "Elva nya ämnen klassas som narkotika eller hälsofarlig vara" [Eleven new substances are classified as narcotics or dangerous goods] (in Swedish). Folkhälsomyndigheten. 28 June 2018.
^ "Förordning (1992:1554) om kontroll av narkotika" [Ordinance (1992:1554) on the control of narcotics]. Riksdagsförvaltningen (in Swedish).
^ "Verordnung des EDI vom 30. Mai 2011 über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien (Betäubungsmittelverzeichnisverordnung, BetmVV-EDI)" [EDI ordinance of May 30, 2011 on the lists of narcotics, psychotropic substances, precursors and auxiliary chemicals (narcotics list ordinance, BetmVV-EDI)] (in German). Der Bundesrat.