3-羟基苯环己哌啶

3-羟基苯环己哌啶
临床资料
其他名称	3-Hydroxyphencyclidine; 3-OH-PCP; PCP-3-OH
法律规范状态
法律规范	加：第一级管制药品; 英：第二级管制药品; 于瑞典及瑞士非法;
识别信息
	IUPAC命名法 3-[1-(Piperidin-1-yl)cyclohexyl]phenol; ;
CAS号	79787-43-2
PubChem CID	133277;
ChemSpider	117583;
UNII	V886QLHNA6;
CompTox Dashboard（英语：CompTox Chemicals Dashboard） (EPA)	DTXSID20229918 ;
化学信息
化学式	C17H25NO
摩尔质量	259.39 g·mol−1
3D模型（JSmol（英语：JSmol））	交互式图像;
	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-羟基苯环己哌啶（别称3-羟基苯环利定，简称：3-HO-PCP）是与苯环己哌啶（英语：Phencyclidine）（苯环利定）相关的芳基环己胺（英语：Arylcyclohexylamine）类离解型药物（英语：Dissociative），现作为狡诈家药物可网上出售。^[1]^[2]

药理

3-HO-PCP在地佐环平（英语：Dizocilpine）（MK-801）的作用下可作为N-甲基-D-天门冬氨酸受体的高亲和性非竞争性拮抗剂（K_i = 30 nM）^[3]^[4]，它比苯环己哌啶（苯环利定）在地佐环平的作用下的亲和性更高（K_i = 250 nM；相差8倍）^[4]。3-HO-PCP在动物试验中亦与μ-鸦片受体（英语：μ-opioid receptor）（MOR；K_i = 39–60 nM）^[3]^[4]^[5]^[6]、κ-鸦片受体（英语：κ-opioid receptor）（KOR；K_i = 140 nM）^[5]与σ₁受体（英语：Sigma-1 receptor）（DOR；K_i = 42 nM；IC₅₀（英语：IC50） = 19 nM）具备高亲和性^[5]^[7]^[8]^[9]，并仅与δ-鸦片受体（英语：δ-opioid receptor）具备低亲和性（K_i = 2,300 nM）^[5]。3-HO-PCP对鸦片受体的高亲和性在芳基环己胺中独一无二，与苯环己哌啶（苯环利定）形成强烈对比：后者对μ-鸦片受体（K_i = 11,000–26,000 nM；相差282至433倍）、κ-鸦片受体（K_i = 4,100 nM）与δ-鸦片受体（K_i = 73,000 nM）的亲和性非常低^[4]^[5]。

有假设称3-HO-PCP可能为人类苯环己哌啶（苯环利定）的代谢产物，惟至今无确切证据表明事实如此。^[10]^[11]

化学

3-HO-PCP可由环己酮和哌啶为原料反应得到。环己酮、哌啶和1,2,3-三唑在甲苯中反应，得到相应的三唑环己哌啶中间体；中间体和3-甲氧基苯基溴化镁或3-甲氧基苯基锂在−78°C的四氢呋喃中反应，三唑基被取代，得到3-甲氧基苯环己哌啶，它再和三溴化硼反应，脱去甲基，得到3-HO-PCP。^[12]

3-HO-PCP为芳基环己胺，其结构类似物包括与之较类似的苯环己哌啶、3-甲氧基苯环己哌啶、4-甲氧基苯环己哌啶（英语：4-MeO-PCP）、3-甲氧基苯环己吗啉（英语：3-MeO-PCMo），以及与之较不类似的氯胺酮、甲氧基胺酮（英语：Methoxyketamine）、3-甲氧基乙环己哌啶（英语：3-MeO-PCE）（3-甲氧基乙环利定）、2-(3-甲氧基苯基)-2-乙胺环己酮（英语：Methoxetamine）、4-二甲基氨基-4-(对甲苯基)环己酮（英语：4-Dimethylamino-4-(p-tolyl)cyclohexanone）。^[3]

合法状态

2012年10月18日，英国药物滥用顾问局（英语：Advisory Council on the Misuse of Drugs）发布一份有关2-(3-甲氧基苯基)-2-乙胺环己酮的报告，称“2-(3-甲氧基苯基)-2-乙胺环己酮的危害相当于《1971年滥用药物法令（英语：Misuse of Drugs Act 1971）》下的第二级管制药品（英语：Drugs controlled by the UK Misuse of Drugs Act）”，惟事实上该法令并无根据药物的危害对药物进行分类。报告亦建议将2-(3-甲氧基苯基)-2-乙胺环己酮的所有类似物均列入为第二级管制药物，并建议同时对所有包括3-HO-PCP在内的所有当时已有的及未有研究的芳基环己胺进行规管。^[13]

3-HO-PCP在瑞典^[14]^[15]与瑞士^[16]被禁用。

参见

氟胺酮
4-酮苯环己哌啶（英语：4-Keto-PCP）
戴路胺（英语：Delucemine）
去甲基曲马多（英语：Desmetramadol）
2-乙胺-2-(3-羟基苯基)环己酮（英语：Hydroxetamine）
4-二甲基氨基-4-(对甲苯基)环己酮（英语：4-Dimethylamino-4-(p-tolyl)cyclohexanone）

参考资料

^ Morris, H.; Wallach, J. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis. 2014, 6 (7–8): 614–632. PMID 24678061. doi:10.1002/dta.1620.
^ Davidsen, Anders Bork; Mardal, Marie; Johansen, Sys Stybe; Dalsgaard, Petur Weihe; Linnet, Kristian. 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. April 2020, 12 (7): 987–993. ISSN 1942-7611. PMID 32311838. doi:10.1002/dta.2807.
^ ^3.0 ^3.1 ^3.2 From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Test Anal. 2014, 6 (7–8): 614–32. PMID 24678061. doi:10.1002/dta.1620.
^ ^4.0 ^4.1 ^4.2 ^4.3 Chemical synthesis and molecular pharmacology of hydroxylated 1-(1-phenylcyclohexyl-piperidine derivatives. J. Med. Chem. 1982, 25 (4): 431–5. PMID 6279847. doi:10.1021/jm00346a019.
^ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 Interaction of two phencyclidine opiate-like derivatives with 3H-opioid binding sites. Eur. J. Pharmacol. 1984, 101 (3–4): 281–4. PMID 6088255. doi:10.1016/0014-2999(84)90171-7.
^ On the opioid nature of phencyclidine and its 3-hydroxy derivative. Eur. J. Pharmacol. 1981, 73 (2–3): 229–33. PMID 6273187. doi:10.1016/0014-2999(81)90097-2.
^ Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes. Mol. Pharmacol. 1985, 27 (1): 46–52. PMID 3965930.
^ [3H]PCP-3-OH and (+)[3H]SKF 10047 binding sites in rat brain membranes: evidence of multiplicity. Eur. J. Pharmacol. 1987, 136 (2): 231–4. PMID 3036548. doi:10.1016/0014-2999(87)90715-1.
^ Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites. Life Sci. 1988, 42 (7): 745–52. PMID 2893238. doi:10.1016/0024-3205(88)90646-7.
^ Biotransformation of phencyclidine. Drug Metab. Rev. 1985, 16 (3): 285–320. PMID 3914938. doi:10.3109/03602538508991437.
^ Quantitation of phencyclidine, its metabolites, and derivatives by gas chromatography with nitrogen-phosphorus detection: application for in vivo and in vitro biotransformation studies. J Anal Toxicol. 1986, 10 (3): 107–15. PMID 3724069. doi:10.1093/jat/10.3.107.
^ Zarantonello, Paola; Bettini, Ezio; Paio, Alfredo; Simoncelli, Chiara; Terreni, Silvia; Cardullo, Francesco. Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2011, 21 (7): 2059–2063. ISSN 0960-894X. doi:10.1016/j.bmcl.2011.02.009.
^ (ACMD) Methoxetamine Report (2012) (PDF). UK Home Office: 14. 2012-10-18 [2015-06-24]. （原始内容存档于2021-08-21）.
^ Elva nya ämnen klassas som narkotika eller hälsofarlig vara. Folkhälsomyndigheten. 28 June 2018 [2021-08-05]. （原始内容存档于2021-03-08）（瑞典语）.
^ Riksdagsförvaltningen. Förordning (1992:1554) om kontroll av narkotika. riksdagen.se. [2021-08-05]. （原始内容存档于2021-08-05）（瑞典语）.
^ Verordnung des EDI vom 30. Mai 2011 über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien (Betäubungsmittelverzeichnisverordnung, BetmVV-EDI). Der Bundesrat. [2021-08-05]. （原始内容存档于2016-01-23）（德语）.

[Morris-1] Morris, H.; Wallach, J. From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis. 2014, 6 (7–8): 614–632. PMID 24678061. doi:10.1002/dta.1620.

[2] Davidsen, Anders Bork; Mardal, Marie; Johansen, Sys Stybe; Dalsgaard, Petur Weihe; Linnet, Kristian. 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. April 2020, 12 (7): 987–993. ISSN 1942-7611. PMID 32311838. doi:10.1002/dta.2807.

[pmid24678061-3] 3.0 ^3.1 ^3.2 From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs. Drug Test Anal. 2014, 6 (7–8): 614–32. PMID 24678061. doi:10.1002/dta.1620.

[pmid6279847-4] 4.0 ^4.1 ^4.2 ^4.3 Chemical synthesis and molecular pharmacology of hydroxylated 1-(1-phenylcyclohexyl-piperidine derivatives. J. Med. Chem. 1982, 25 (4): 431–5. PMID 6279847. doi:10.1021/jm00346a019.

[pmid6088255-5] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 Interaction of two phencyclidine opiate-like derivatives with 3H-opioid binding sites. Eur. J. Pharmacol. 1984, 101 (3–4): 281–4. PMID 6088255. doi:10.1016/0014-2999(84)90171-7.

[pmid6273187-6] On the opioid nature of phencyclidine and its 3-hydroxy derivative. Eur. J. Pharmacol. 1981, 73 (2–3): 229–33. PMID 6273187. doi:10.1016/0014-2999(81)90097-2.

[pmid3965930-7] Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes. Mol. Pharmacol. 1985, 27 (1): 46–52. PMID 3965930.

[pmid3036548-8] [3H]PCP-3-OH and (+)[3H]SKF 10047 binding sites in rat brain membranes: evidence of multiplicity. Eur. J. Pharmacol. 1987, 136 (2): 231–4. PMID 3036548. doi:10.1016/0014-2999(87)90715-1.

[pmid2893238-9] Pharmacological specificity of some psychotomimetic and antipsychotic agents for the sigma and PCP binding sites. Life Sci. 1988, 42 (7): 745–52. PMID 2893238. doi:10.1016/0024-3205(88)90646-7.

[pmid3914938-10] Biotransformation of phencyclidine. Drug Metab. Rev. 1985, 16 (3): 285–320. PMID 3914938. doi:10.3109/03602538508991437.

[pmid3724069-11] Quantitation of phencyclidine, its metabolites, and derivatives by gas chromatography with nitrogen-phosphorus detection: application for in vivo and in vitro biotransformation studies. J Anal Toxicol. 1986, 10 (3): 107–15. PMID 3724069. doi:10.1093/jat/10.3.107.

[12] Zarantonello, Paola; Bettini, Ezio; Paio, Alfredo; Simoncelli, Chiara; Terreni, Silvia; Cardullo, Francesco. Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists. Bioorganic & Medicinal Chemistry Letters. 2011, 21 (7): 2059–2063. ISSN 0960-894X. doi:10.1016/j.bmcl.2011.02.009.

[ACMD_MXE_report-13] (ACMD) Methoxetamine Report (2012) (PDF). UK Home Office: 14. 2012-10-18 [2015-06-24]. （原始内容存档于2021-08-21）.

[14] Elva nya ämnen klassas som narkotika eller hälsofarlig vara. Folkhälsomyndigheten. 28 June 2018 [2021-08-05]. （原始内容存档于2021-03-08）（瑞典语）.

[15] Riksdagsförvaltningen. Förordning (1992:1554) om kontroll av narkotika. riksdagen.se. [2021-08-05]. （原始内容存档于2021-08-05）（瑞典语）.

[16] Verordnung des EDI vom 30. Mai 2011 über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien (Betäubungsmittelverzeichnisverordnung, BetmVV-EDI). Der Bundesrat. [2021-08-05]. （原始内容存档于2016-01-23）（德语）.

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