3-HO-PCP acts as a high-affinityuncompetitive antagonist of theNMDA receptor via thedizocilpine (MK-801) site (Ki = 30 nM).[1][3] It has much higher affinity than PCP for this site (Ki = 250 nM, for comparison; 8-fold difference).[3] The drug also has high affinity for theμ-opioid receptor (MOR) (Ki = 39–60 nM) in animal test subjects,[1][3][4][5] theκ-opioid receptor (KOR) (Ki = 140 nM),[4] and thesigmaσ1 receptor (Ki = 42 nM;IC50 = 19 nM),[4][6][7][8] whereas it has only low affinity for theδ-opioid receptor (Ki = 2,300 nM).[4] The high affinity of 3-HO-PCP foropioid receptors is unique among arylcyclohexylamines and is in contrast to PCP, which has only very low affinity for the MOR (Ki = 11,000–26,000 nM; 282- to 433-fold difference) and the other opioid receptors (Ki = 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 ametabolite of PCP in humans, there is no evidence that this is the case.[9][10] 3-HO-PCP is a metabolite of3-MeO-PCP.[11]
3-HO-PCP was mentioned by a chemist under the pseudonym "John Q. Beagle" in 1999 in a post onThe Hive.[1] The psychoactive effects of 3-HO-PCP have been described byBluelight users even before its availability as a research chemical in 2009.[1]
On October 18, 2012, theAdvisory Council on the Misuse of Drugs in theUnited Kingdom released a report aboutmethoxetamine, saying that the "harms of methoxetamine are commensurate withClass B of theMisuse 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]
^abcdefgMorris 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.PMID24678061.
^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.PMID32311838.S2CID216047397.
^abcdKamenka 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.PMID6279847.
^abcdeJohnson 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.PMID6088255.
^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.PMID6273187.
^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.doi:10.1016/S0026-895X(25)11457-0.PMID3965930.
^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.PMID3036548.
^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.PMID2893238.
^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.PMID3724069.
^Wallach J, Brandt SD (2018). "Phencyclidine-Based New Psychoactive Substances". In Maurer HH, Brandt SD (eds.).Handbook of Experimental Pharmacology. Vol. 252. Cham: Springer International Publishing=. pp. 261–303.doi:10.1007/164_2018_124.ISBN978-3-030-10561-7.PMID30105474.
