3-羥基苯環己哌啶

化合物

3-羥基苯環己哌啶(別稱3-羥基苯環利定,簡稱:3-HO-PCP)是與苯環己哌啶英语Phencyclidine(苯環利定)相關的芳基環己胺英语Arylcyclohexylamine解離型藥物英语Dissociative,現作為狡詐家藥物可網上出售。[1][2]

3-羥基苯環己哌啶
臨床資料
其他名稱3-Hydroxyphencyclidine; 3-OH-PCP; PCP-3-OH
法律規範狀態
法律規範
  • 第一級管制藥品
  • 第二級管制藥品
  • 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

藥理

3-HO-PCP在地佐環平英语Dizocilpine(MK-801)的作用下可作為N-甲基-D-天門冬胺酸受體的高親和性非競爭性拮抗劑(Ki = 30 nM)[3][4],它比苯環己哌啶(苯環利定)在地佐環平的作用下的親和性更高(Ki = 250 nM;相差8倍)[4]。3-HO-PCP在動物試驗中亦與μ-鴉片受體英语μ-opioid receptor(MOR;Ki = 39–60 nM)[3][4][5][6]κ-鴉片受體英语κ-opioid receptor(KOR;Ki = 140 nM)[5]σ1受體英语Sigma-1 receptor(DOR;Ki = 42 nM;IC50英语IC50 = 19 nM)具備高親和性[5][7][8][9],並僅與δ-鴉片受體英语δ-opioid receptor具備低親和性(Ki = 2,300 nM)[5]。3-HO-PCP對鴉片受體的高親和性在芳基環己胺中獨一無二,與苯環己哌啶(苯環利定)形成強烈對比:後者對μ-鴉片受體(Ki = 11,000–26,000 nM;相差282至433倍)、κ-鴉片受體(Ki = 4,100 nM)與δ-鴉片受體(Ki = 73,000 nM)的親和性非常低[4][5]

有假設稱3-HO-PCP可能為人類苯環己哌啶(苯環利定)的代謝產物,惟至今無確切證據表明事實如此。[10][11]

化學

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,得到相应的三唑環己哌啶中间体;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-甲氧基苯環己哌啶,它再和三溴化硼反应,脱去甲基,得到3-HO-PCP。[12]

3-HO-PCP為芳基環己胺,其结构类似物包括與之較類似的苯環己哌啶、3-甲氧基苯環己哌啶4-甲氧基苯環己哌啶英语4-MeO-PCP3-甲氧基苯環己嗎啉英语3-MeO-PCMo,以及與之較不類似的氯胺酮甲氧基胺酮英语Methoxyketamine3-甲氧基乙環己哌啶英语3-MeO-PCE(3-甲氧基乙環利定)、2-(3-甲氧基苯基)-2-乙胺環己酮英语Methoxetamine4-二甲基氨基-4-(對甲苯基)環己酮英语4-Dimethylamino-4-(p-tolyl)cyclohexanone[3]

合法狀態

2012年10月18日,英国藥物濫用顧問局英语Advisory Council on the Misuse of Drugs發佈一份有關2-(3-甲氧基苯基)-2-乙胺環己酮的報告,稱“2-(3-甲氧基苯基)-2-乙胺環己酮的危害相當於《1971年濫用藥物法令英语Misuse of Drugs Act 1971》下的第二級管制藥品英语Drugs controlled by the UK Misuse of Drugs Act”,惟事實上該法令並無根據藥物的危害對藥物進行分類。報告亦建議將2-(3-甲氧基苯基)-2-乙胺環己酮的所有類似物均列入為第二級管制藥物,並建議同時對所有包括3-HO-PCP在內的所有當時已有的及未有研究的芳基環己胺進行規管。[13]

3-HO-PCP在瑞典[14][15]與瑞士[16]被禁用。

參見

參考資料

  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).