3-羟基苯环己哌啶

化合物

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离解型药物英语Dissociative,现作为狡诈家药物可网上出售。[1][2]

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
  • 第一级管制药品
  • 第二级管制药品
  • 瑞典瑞士非法
识别信息
  • 3-[1-(Piperidin-1-yl)cyclohexyl]phenol
CAS号79787-43-2  checkY
PubChem CID
ChemSpider
UNII
CompTox Dashboard英语CompTox Chemicals Dashboard (EPA)
化学信息
化学式C17H25NO
摩尔质量259.39 g·mol−1
3D模型(JSmol英语JSmol
  • c1cc(cc(c1)O)C2(CCCCC2)N3CCCCC3
  • 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

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(Ki = 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(Ki = 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;Ki = 39–60 nM)[3][4][5][6]κ-鸦片受体英语κ-opioid receptor(KOR;Ki = 140 nM)[5]σ1受体英语Sigma-1 receptor(DOR;Ki = 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(Ki = 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(Ki = 11,000–26,000 nM;相差282至433倍)、κ-鸦片受体(Ki = 4,100 nM)与δ-鸦片受体(Ki = 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-PCP3-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Methoxyketamine3-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Methoxetamine4-二甲基氨基-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

参考资料

  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. 
  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. 
  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. 
  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. 
  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. 
  7. ^ Characterization of specific binding sites for [3H](d)-N-allylnormetazocine in rat brain membranes. Mol. Pharmacol. 1985, 27 (1): 46–52. PMID 3965930. 
  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. 
  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. 
  10. ^ Biotransformation of phencyclidine. Drug Metab. Rev. 1985, 16 (3): 285–320. PMID 3914938. doi:10.3109/03602538508991437. 
  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. 
  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).