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Erschienen in: Forensic Toxicology 2/2016

Open Access 27.04.2016 | Original Article

The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities

verfasst von: Mitchell Longworth, Samuel D. Banister, James B. C. Mack, Michelle Glass, Mark Connor, Michael Kassiou

Erschienen in: Forensic Toxicology | Ausgabe 2/2016

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Abstract

Indazole-derived synthetic cannabinoids (SCs) featuring an alkyl substituent at the 1-position and l-valinamide at the 3-carboxamide position (e.g., AB-CHMINACA) have been identified by forensic chemists around the world, and are associated with serious adverse health effects. Regioisomerism is possible for indazole SCs, with the 2-alkyl-2H-indazole regioisomer of AB-CHMINACA recently identified in SC products in Japan. It is unknown whether this regiosiomer represents a manufacturing impurity arising as a synthetic byproduct, or was intentionally synthesized as a cannabimimetic agent. This study reports the synthesis, analytical characterization, and pharmacological evaluation of commonly encountered indazole SCs AB-CHMINACA, AB-FUBINACA, AB-PINACA, 5F-AB-PINACA and their corresponding 2-alkyl-2H-indazole regioisomers. Both regioisomers of each SC were prepared from a common precursor, and the physical properties, 1H and 13C nuclear magnetic resonance spectroscopy, gas chromatography–mass spectrometry, and ultraviolet–visible spectroscopy of all SC compounds are described. Additionally, AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA were found to act as high potency agonists at CB1 (EC50 = 2.1–11.6 nM) and CB2 (EC50 = 5.6–21.1 nM) receptors in fluorometric assays, while the corresponding 2-alkyl-2H-indazole regioisomers demonstrated low potency (micromolar) agonist activities at both receptors. Taken together, these data suggest that 2-alkyl-2H-indazole regioisomers of AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are likely to be encountered by forensic chemists and toxicologists as the result of improper purification during the clandestine synthesis of 1-alkyl-1H-indazole regioisomers, and can be distinguished by differences in gas chromatography–mass spectrometry fragmentation pattern.
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Literatur
1.
Zurück zum Zitat Brandt SD, King LA, Evans-Brown M (2014) The new drug phenomenon. Drug Test Anal 6:587–597 CrossRefPubMed Brandt SD, King LA, Evans-Brown M (2014) The new drug phenomenon. Drug Test Anal 6:587–597 CrossRefPubMed
2.
Zurück zum Zitat Auwärter V, Dresen S, Weinmann W, Muller M, Putz M, Ferreiros N (2009) ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 44:832–837 CrossRefPubMed Auwärter V, Dresen S, Weinmann W, Muller M, Putz M, Ferreiros N (2009) ‘Spice’ and other herbal blends: harmless incense or cannabinoid designer drugs? J Mass Spectrom 44:832–837 CrossRefPubMed
3.
Zurück zum Zitat Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y (2009) Identification of a cannabimimetic indole as a designer drug in a herbal product. Forensic Toxicol 27:61–66 CrossRef Uchiyama N, Kikura-Hanajiri R, Kawahara N, Goda Y (2009) Identification of a cannabimimetic indole as a designer drug in a herbal product. Forensic Toxicol 27:61–66 CrossRef
4.
Zurück zum Zitat European Monitoring Centre for Drugs and Drug Addiction (2015) EMCDDA–Europol 2014 annual report on the implementation of council decision 2005/387/JHA, implementation reports. Publications Office of the European Union, Luxembourg. doi: 10.​2810/​112317. Accessed 1 Feb 1, 2016 European Monitoring Centre for Drugs and Drug Addiction (2015) EMCDDA–Europol 2014 annual report on the implementation of council decision 2005/387/JHA, implementation reports. Publications Office of the European Union, Luxembourg. doi: 10.​2810/​112317. Accessed 1 Feb 1, 2016
5.
Zurück zum Zitat Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2014) Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan. Drug Test Anal 6:832–839 CrossRefPubMed Kikura-Hanajiri R, Uchiyama N, Kawamura M, Goda Y (2014) Changes in the prevalence of new psychoactive substances before and after the introduction of the generic scheduling of synthetic cannabinoids in Japan. Drug Test Anal 6:832–839 CrossRefPubMed
6.
Zurück zum Zitat Zawilska JB, Andrzejczak D (2015) Next generation of novel psychoactive substances on the horizon—a complex problem to face. Drug Alcohol Depend 157:1–17 CrossRefPubMed Zawilska JB, Andrzejczak D (2015) Next generation of novel psychoactive substances on the horizon—a complex problem to face. Drug Alcohol Depend 157:1–17 CrossRefPubMed
7.
Zurück zum Zitat Blakey K, Boyd S, Atkinson S, Wolf J, Slottje PM, Goodchild K, McGowan J (2015) Identification of the novel synthetic cannabimimetic 8-quinolinyl 4-methyl-3-(1-piperidinylsulfonyl)benzoate (QMPSB) and other designer drugs in herbal incense. Forensic Sci Int 260:40–53 CrossRefPubMed Blakey K, Boyd S, Atkinson S, Wolf J, Slottje PM, Goodchild K, McGowan J (2015) Identification of the novel synthetic cannabimimetic 8-quinolinyl 4-methyl-3-(1-piperidinylsulfonyl)benzoate (QMPSB) and other designer drugs in herbal incense. Forensic Sci Int 260:40–53 CrossRefPubMed
8.
Zurück zum Zitat Kondrasenko AA, Goncharov EV, Dugaev KP, Rubaylo AI (2015) CBL-2201. Report on a new designer drug: naphth-1-yl 1-(5-fluoropentyl)-1 H-indole-3-carboxylate. Forensic Sci Int 257:209–213 CrossRefPubMed Kondrasenko AA, Goncharov EV, Dugaev KP, Rubaylo AI (2015) CBL-2201. Report on a new designer drug: naphth-1-yl 1-(5-fluoropentyl)-1 H-indole-3-carboxylate. Forensic Sci Int 257:209–213 CrossRefPubMed
9.
Zurück zum Zitat McLaughlin G, Morris N, Kavanagh PV, Power JD, Twamley B, O’Brien J, Talbot B, Dowling G, Brandt SD (2015) The synthesis and characterization of the ‘research chemical’ N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1 H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer. Drug Test Anal. doi: 10.​1002/​dta.​1864 McLaughlin G, Morris N, Kavanagh PV, Power JD, Twamley B, O’Brien J, Talbot B, Dowling G, Brandt SD (2015) The synthesis and characterization of the ‘research chemical’ N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1 H-pyrazole-5-carboxamide (3,5-AB-CHMFUPPYCA) and differentiation from its 5,3-regioisomer. Drug Test Anal. doi: 10.​1002/​dta.​1864
10.
Zurück zum Zitat Uchiyama N, Asakawa K, Kikura-Hanajiri R, Tsutsumi T, Hakamatsuka T (2015) A new pyrazole-carboxamide type synthetic cannabinoid AB-CHFUPYCA [ N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1 H-pyrazole-5-carboxamide] identified in illegal products. Forensic Toxicol 33:367–373 CrossRef Uchiyama N, Asakawa K, Kikura-Hanajiri R, Tsutsumi T, Hakamatsuka T (2015) A new pyrazole-carboxamide type synthetic cannabinoid AB-CHFUPYCA [ N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1 H-pyrazole-5-carboxamide] identified in illegal products. Forensic Toxicol 33:367–373 CrossRef
11.
Zurück zum Zitat Westphal F, Sönnichsen FD, Knecht S, Auwärter V, Huppertz L (2015) Two thiazolylindoles and a benzimidazole: novel compounds on the designer drug market with potential cannabinoid receptor activity. Forensic Sci Int 249:133–147 CrossRefPubMed Westphal F, Sönnichsen FD, Knecht S, Auwärter V, Huppertz L (2015) Two thiazolylindoles and a benzimidazole: novel compounds on the designer drug market with potential cannabinoid receptor activity. Forensic Sci Int 249:133–147 CrossRefPubMed
12.
Zurück zum Zitat Qian Z, Hua Z, Liu C, Jia W (2016) Four types of cannabimimetic indazole and indole derivatives, ADB-BINACA, AB-FUBICA, ADB-FUBICA, and AB-BICA, identified as new psychoactive substances. Forensic Toxicol 34:133–143 CrossRefPubMed Qian Z, Hua Z, Liu C, Jia W (2016) Four types of cannabimimetic indazole and indole derivatives, ADB-BINACA, AB-FUBICA, ADB-FUBICA, and AB-BICA, identified as new psychoactive substances. Forensic Toxicol 34:133–143 CrossRefPubMed
13.
Zurück zum Zitat Shevyrin V, Melkozerov V, Eltsov O, Shafran Y, Morzherin Y (2016) Synthetic cannabinoid 3-benzyl-5-[1-(2-pyrrolidin-1-ylethyl)-1 H-indol-3-yl]-1,2,4-oxadiazole. The first detection in illicit market of new psychoactive substances. Forensic Sci Int 259:95–100 CrossRefPubMed Shevyrin V, Melkozerov V, Eltsov O, Shafran Y, Morzherin Y (2016) Synthetic cannabinoid 3-benzyl-5-[1-(2-pyrrolidin-1-ylethyl)-1 H-indol-3-yl]-1,2,4-oxadiazole. The first detection in illicit market of new psychoactive substances. Forensic Sci Int 259:95–100 CrossRefPubMed
14.
Zurück zum Zitat Lobo Vicente J, Chassaigne H, Holland MV, Reniero F, Kolar K, Tirendi S, Vandecasteele I, Vinckier I, Guillou C (2016) Systematic analytical characterization of new psychoactive substances: a case study. Forensic Sci Int 265:107–115 CrossRefPubMed Lobo Vicente J, Chassaigne H, Holland MV, Reniero F, Kolar K, Tirendi S, Vandecasteele I, Vinckier I, Guillou C (2016) Systematic analytical characterization of new psychoactive substances: a case study. Forensic Sci Int 265:107–115 CrossRefPubMed
15.
Zurück zum Zitat Buchler IP, Hayes MJ, Hedge SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK (2009) Indazole derivatives as CB1 receptor modulators and their preparation and use in treatment of diseases. Patent WO 2009/106980 Buchler IP, Hayes MJ, Hedge SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK (2009) Indazole derivatives as CB1 receptor modulators and their preparation and use in treatment of diseases. Patent WO 2009/106980
16.
Zurück zum Zitat Buchler IP, Hayes MJ, Hedge SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK (2009) Indazole derivatives as CB1 receptor modulators and their preparation and use in the treatment of CB1-mediated diseases. Patent WO 2009/106982 Buchler IP, Hayes MJ, Hedge SG, Hockerman SL, Jones DE, Kortum SW, Rico JG, Tenbrink RE, Wu KK (2009) Indazole derivatives as CB1 receptor modulators and their preparation and use in the treatment of CB1-mediated diseases. Patent WO 2009/106982
17.
Zurück zum Zitat Centers for Disease Control and Prevention (2013) Notes from the field: severe illness associated with synthetic cannabinoid use-Brunswick, Georgia, 2013. Morb Mortal Wkly Rep 62:939 Centers for Disease Control and Prevention (2013) Notes from the field: severe illness associated with synthetic cannabinoid use-Brunswick, Georgia, 2013. Morb Mortal Wkly Rep 62:939
18.
Zurück zum Zitat Centers for Disease Control and Prevention (2013) Notes from the field: severe illness associated with reported use of synthetic marijuana-Colorado, August–September 2013. Morb Mortal Wkly Rep 62:1016–1017 Centers for Disease Control and Prevention (2013) Notes from the field: severe illness associated with reported use of synthetic marijuana-Colorado, August–September 2013. Morb Mortal Wkly Rep 62:1016–1017
19.
Zurück zum Zitat Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2014) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53 CrossRef Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2014) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53 CrossRef
20.
Zurück zum Zitat Monte AA, Bronstein AC, Cao DJ, Heard KJ, Hoppe JA, Hoyte CO, Iwanicki JL, Lavonas EJ (2014) An outbreak of exposure to a novel synthetic cannabinoid. N Engl J Med 370:389–390 CrossRefPubMedPubMedCentral Monte AA, Bronstein AC, Cao DJ, Heard KJ, Hoppe JA, Hoyte CO, Iwanicki JL, Lavonas EJ (2014) An outbreak of exposure to a novel synthetic cannabinoid. N Engl J Med 370:389–390 CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Hess C, Stockhausen S, Kernbach-Wighton G, Madea B (2015) Death due to diabetic ketoacidosis: induction by the consumption of synthetic cannabinoids? Forensic Sci Int 257:e6–e11 CrossRefPubMed Hess C, Stockhausen S, Kernbach-Wighton G, Madea B (2015) Death due to diabetic ketoacidosis: induction by the consumption of synthetic cannabinoids? Forensic Sci Int 257:e6–e11 CrossRefPubMed
22.
Zurück zum Zitat Schwartz MD, Trecki J, Edison LA, Steck AR, Arnold JK, Gerona RR (2015) A common source outbreak of severe delirium associated with exposure to the novel synthetic cannabinoid ADB-PINACA. J Emerg Med 48:573–580 CrossRefPubMed Schwartz MD, Trecki J, Edison LA, Steck AR, Arnold JK, Gerona RR (2015) A common source outbreak of severe delirium associated with exposure to the novel synthetic cannabinoid ADB-PINACA. J Emerg Med 48:573–580 CrossRefPubMed
23.
Zurück zum Zitat Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Shafran Y, Morzherin Y, Lebedev AT (2015) Identification and analytical characteristics of synthetic cannabinoids with an indazole-3-carboxamide structure bearing a N-1-methoxycarbonylalkyl group. Anal Bioanal Chem 407:6301–6315 CrossRefPubMed Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Shafran Y, Morzherin Y, Lebedev AT (2015) Identification and analytical characteristics of synthetic cannabinoids with an indazole-3-carboxamide structure bearing a N-1-methoxycarbonylalkyl group. Anal Bioanal Chem 407:6301–6315 CrossRefPubMed
24.
Zurück zum Zitat Labay LM, Caruso JL, Gilson TP, Phipps RJ, Knight LD, Lemos NP, McIntyre IM, Stoppacher R, Tormos LM, Wiens AL, Williams E, Logan BK (2016) Synthetic cannabinoid drug use as a cause or contributory cause of death. Forensic Sci Int 260:31–39 CrossRefPubMed Labay LM, Caruso JL, Gilson TP, Phipps RJ, Knight LD, Lemos NP, McIntyre IM, Stoppacher R, Tormos LM, Wiens AL, Williams E, Logan BK (2016) Synthetic cannabinoid drug use as a cause or contributory cause of death. Forensic Sci Int 260:31–39 CrossRefPubMed
26.
Zurück zum Zitat Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281 CrossRef Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl)benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281 CrossRef
27.
Zurück zum Zitat Langer N, Lindigkeit R, Schiebel H-M, Papke U, Ernst L, Beuerle T (2015) Identification and quantification of synthetic cannabinoids in “spice-like” herbal mixtures: update of the German situation for the spring of 2015. Forensic Toxicol 34:94–107 CrossRef Langer N, Lindigkeit R, Schiebel H-M, Papke U, Ernst L, Beuerle T (2015) Identification and quantification of synthetic cannabinoids in “spice-like” herbal mixtures: update of the German situation for the spring of 2015. Forensic Toxicol 34:94–107 CrossRef
28.
Zurück zum Zitat Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1 H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1 H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products. Forensic Toxicol 31:93–100 CrossRef Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1 H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1 H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products. Forensic Toxicol 31:93–100 CrossRef
29.
Zurück zum Zitat European Monitoring Centre for Drugs and Drug Addiction (2014) EMCDDA–Europol 2013 annual report on the implementation of council decision 2005/387/JHA, implementation reports. Publications Office of the European Union, Luxembourg. doi: 10.​2810/​51986. Accessed 1 Feb 2016 European Monitoring Centre for Drugs and Drug Addiction (2014) EMCDDA–Europol 2013 annual report on the implementation of council decision 2005/387/JHA, implementation reports. Publications Office of the European Union, Luxembourg. doi: 10.​2810/​51986. Accessed 1 Feb 2016
30.
Zurück zum Zitat Wilkinson SM, Banister SD, Kassiou M (2015) Bioisosteric fluorine in the clandestine design of synthetic cannabinoids. Aust J Chem 68:4–8 CrossRef Wilkinson SM, Banister SD, Kassiou M (2015) Bioisosteric fluorine in the clandestine design of synthetic cannabinoids. Aust J Chem 68:4–8 CrossRef
31.
Zurück zum Zitat Banister SD, Moir M, Stuart J, Kevin RC, Wood KE, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Glass M, Connor M, McGregor IS, Kassiou M (2015) Pharmacology of indole and indazole synthetic cannabinoid designer drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. ACS Chem Neurosci 6:1546–1559 CrossRefPubMed Banister SD, Moir M, Stuart J, Kevin RC, Wood KE, Longworth M, Wilkinson SM, Beinat C, Buchanan AS, Glass M, Connor M, McGregor IS, Kassiou M (2015) Pharmacology of indole and indazole synthetic cannabinoid designer drugs AB-FUBINACA, ADB-FUBINACA, AB-PINACA, ADB-PINACA, 5F-AB-PINACA, 5F-ADB-PINACA, ADBICA, and 5F-ADBICA. ACS Chem Neurosci 6:1546–1559 CrossRefPubMed
32.
Zurück zum Zitat Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing Δ 9-tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 354:328–339 CrossRefPubMed Wiley JL, Marusich JA, Lefever TW, Antonazzo KR, Wallgren MT, Cortes RA, Patel PR, Grabenauer M, Moore KN, Thomas BF (2015) AB-CHMINACA, AB-PINACA, and FUBIMINA: affinity and potency of novel synthetic cannabinoids in producing Δ 9-tetrahydrocannabinol-like effects in mice. J Pharmacol Exp Ther 354:328–339 CrossRefPubMed
33.
Zurück zum Zitat Gatch MB, Forster MJ (2015) Δ 9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market. Behav Pharmacol 26:460–468 CrossRefPubMed Gatch MB, Forster MJ (2015) Δ 9-Tetrahydrocannabinol-like effects of novel synthetic cannabinoids found on the gray market. Behav Pharmacol 26:460–468 CrossRefPubMed
34.
Zurück zum Zitat Thornton SL, Akpunonu P, Glauner K, Hoehn KS, Gerona R (2015) Unintentional pediatric exposure to a synthetic cannabinoid (AB-PINACA) resulting in coma and intubation. Ann Emerg Med 66:343–344 CrossRefPubMed Thornton SL, Akpunonu P, Glauner K, Hoehn KS, Gerona R (2015) Unintentional pediatric exposure to a synthetic cannabinoid (AB-PINACA) resulting in coma and intubation. Ann Emerg Med 66:343–344 CrossRefPubMed
35.
Zurück zum Zitat Trecki J, Gerona RR, Schwartz MD (2015) Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 373:103–107 CrossRefPubMed Trecki J, Gerona RR, Schwartz MD (2015) Synthetic cannabinoid-related illnesses and deaths. N Engl J Med 373:103–107 CrossRefPubMed
36.
Zurück zum Zitat Tyndall JA, Gerona R, De Portu G, Trecki J, Elie MC, Lucas J, Slish J, Rand K, Bazydlo L, Holder M, Ryan MF, Myers P, Iovine N, Plourde M, Weeks E, Hanley JR, Endres G, St Germaine D, Dobrowolski PJ, Schwartz M (2015) An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA. Clin Toxicol 53:950–956 CrossRef Tyndall JA, Gerona R, De Portu G, Trecki J, Elie MC, Lucas J, Slish J, Rand K, Bazydlo L, Holder M, Ryan MF, Myers P, Iovine N, Plourde M, Weeks E, Hanley JR, Endres G, St Germaine D, Dobrowolski PJ, Schwartz M (2015) An outbreak of acute delirium from exposure to the synthetic cannabinoid AB-CHMINACA. Clin Toxicol 53:950–956 CrossRef
37.
Zurück zum Zitat Drug Enforcement Administration, Department of Justice (2014) Schedules of controlled substances: temporary placement of four synthetic cannabinoids into Schedule I. Final order. Fed Regist 79:7577–7582 Drug Enforcement Administration, Department of Justice (2014) Schedules of controlled substances: temporary placement of four synthetic cannabinoids into Schedule I. Final order. Fed Regist 79:7577–7582
38.
Zurück zum Zitat Drug Enforcement Administration, Department of Justice (2015) Schedules of controlled substances: temporary placement of three synthetic cannabinoids into schedule I. Final order. Fed Regist 80:5042–5047 Drug Enforcement Administration, Department of Justice (2015) Schedules of controlled substances: temporary placement of three synthetic cannabinoids into schedule I. Final order. Fed Regist 80:5042–5047
39.
Zurück zum Zitat Erratico C, Negreira N, Norouzizadeh H, Covaci A, Neels H, Maudens K, van Nuijs AL (2015) In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA. Drug Test Anal 7:866–876 CrossRefPubMed Erratico C, Negreira N, Norouzizadeh H, Covaci A, Neels H, Maudens K, van Nuijs AL (2015) In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA. Drug Test Anal 7:866–876 CrossRefPubMed
40.
Zurück zum Zitat Wurita A, Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K (2016) Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser. Leg Med 19:113–118 CrossRef Wurita A, Hasegawa K, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Suzuki O, Watanabe K (2016) Identification and quantification of metabolites of AB-CHMINACA in a urine specimen of an abuser. Leg Med 19:113–118 CrossRef
41.
Zurück zum Zitat Takayama T, Suzuki M, Todoroki K, Inoue K, Min JZ, Kikura-Hanajiri R, Goda Y, Toyo’oka T (2014) UPLC/ESI-MS/MS-based determination of metabolism of several new illicit drugs, ADB-FUBINACA, AB-FUBINACA, AB-PINACA, QUPIC, 5F-QUPIC and α-PVT, by human liver microsome. Biomed Chromatogr 28:831–838 CrossRefPubMed Takayama T, Suzuki M, Todoroki K, Inoue K, Min JZ, Kikura-Hanajiri R, Goda Y, Toyo’oka T (2014) UPLC/ESI-MS/MS-based determination of metabolism of several new illicit drugs, ADB-FUBINACA, AB-FUBINACA, AB-PINACA, QUPIC, 5F-QUPIC and α-PVT, by human liver microsome. Biomed Chromatogr 28:831–838 CrossRefPubMed
42.
Zurück zum Zitat Castaneto MS, Wohlfarth A, Pang S, Zhu M, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol 33:295–310 CrossRef Castaneto MS, Wohlfarth A, Pang S, Zhu M, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry. Forensic Toxicol 33:295–310 CrossRef
43.
Zurück zum Zitat Vikingsson S, Green H, Brinkhagen L, Mukhtar S, Josefsson M (2015) Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. Drug Test Anal. doi: 10.​1002/​dta.​1896 PubMed Vikingsson S, Green H, Brinkhagen L, Mukhtar S, Josefsson M (2015) Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. Drug Test Anal. doi: 10.​1002/​dta.​1896 PubMed
44.
Zurück zum Zitat Hsin-Hung Chen M, Dip A, Ahmed M, Tan ML, Walterscheid JP, Sun H, Teng BB, Mozayani A (2016) Detection and characterization of the effect of AB-FUBINACA and its metabolites in a rat model. J Cell Biochem 117:1033–1043 CrossRefPubMed Hsin-Hung Chen M, Dip A, Ahmed M, Tan ML, Walterscheid JP, Sun H, Teng BB, Mozayani A (2016) Detection and characterization of the effect of AB-FUBINACA and its metabolites in a rat model. J Cell Biochem 117:1033–1043 CrossRefPubMed
45.
Zurück zum Zitat Jang M, Shin I, Kim J, Yang W (2015) Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry. Forensic Toxicol 33:221–234 CrossRef Jang M, Shin I, Kim J, Yang W (2015) Simultaneous quantification of 37 synthetic cannabinoid metabolites in human urine by liquid chromatography-tandem mass spectrometry. Forensic Toxicol 33:221–234 CrossRef
46.
Zurück zum Zitat Wohlfarth A, Castaneto MS, Zhu M, Pang S, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Pentylindole/pentylindazole synthetic cannabinoids and their 5-fluoro analogs produce different primary metabolites: metabolite profiling for AB-PINACA and 5F-AB-PINACA. AAPS J 17:660–677 CrossRefPubMedPubMedCentral Wohlfarth A, Castaneto MS, Zhu M, Pang S, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Pentylindole/pentylindazole synthetic cannabinoids and their 5-fluoro analogs produce different primary metabolites: metabolite profiling for AB-PINACA and 5F-AB-PINACA. AAPS J 17:660–677 CrossRefPubMedPubMedCentral
47.
Zurück zum Zitat Namera A, Kawamura M, Nakamoto A, Saito T, Nagao M (2015) Comprehensive review of the detection methods for synthetic cannabinoids and cathinones. Forensic Toxicol 33:175–194 CrossRefPubMedPubMedCentral Namera A, Kawamura M, Nakamoto A, Saito T, Nagao M (2015) Comprehensive review of the detection methods for synthetic cannabinoids and cathinones. Forensic Toxicol 33:175–194 CrossRefPubMedPubMedCentral
48.
Zurück zum Zitat DeRuiter J, Smith FT, Abdel-Hay K, Clark CR (2014) Analytical differentiation of 1-alkyl-3-acylindoles and 1-acyl-3-alkylindoles: isomeric synthetic cannabinoids. Anal Chem 86:3801–3808 CrossRefPubMed DeRuiter J, Smith FT, Abdel-Hay K, Clark CR (2014) Analytical differentiation of 1-alkyl-3-acylindoles and 1-acyl-3-alkylindoles: isomeric synthetic cannabinoids. Anal Chem 86:3801–3808 CrossRefPubMed
49.
Zurück zum Zitat Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Morzherin Y, Shafran Y (2014) 3-Naphthoylindazoles and 2-naphthoylbenzoimidazoles as novel chemical groups of synthetic cannabinoids: chemical structure elucidation, analytical characteristics and identification of the first representatives in smoke mixtures. Forensic Sci Int 242:72–80 CrossRefPubMed Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Morzherin Y, Shafran Y (2014) 3-Naphthoylindazoles and 2-naphthoylbenzoimidazoles as novel chemical groups of synthetic cannabinoids: chemical structure elucidation, analytical characteristics and identification of the first representatives in smoke mixtures. Forensic Sci Int 242:72–80 CrossRefPubMed
50.
Zurück zum Zitat Girreser U, Rosner P, Vasilev A (2015) Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted C NMR shifts—a case study. Drug Test Anal. doi: 10.​1002/​dta.​1820 Girreser U, Rosner P, Vasilev A (2015) Structure elucidation of the designer drug N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-3-(4-fluorophenyl)-pyrazole-5-carboxamide and the relevance of predicted C NMR shifts—a case study. Drug Test Anal. doi: 10.​1002/​dta.​1820
51.
Zurück zum Zitat Uchiyama N, Shimokawa Y, Kikura-Hanajiri R, Demizu Y, Goda Y, Hakamatsuka T (2015) A synthetic cannabinoid FDU-NNEI, two 2-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products. Forensic Toxicol 33:244–259 CrossRefPubMedPubMedCentral Uchiyama N, Shimokawa Y, Kikura-Hanajiri R, Demizu Y, Goda Y, Hakamatsuka T (2015) A synthetic cannabinoid FDU-NNEI, two 2-indazole isomers of synthetic cannabinoids AB-CHMINACA and NNEI indazole analog (MN-18), a phenethylamine derivative N-OH-EDMA, and a cathinone derivative dimethoxy-α-PHP, newly identified in illegal products. Forensic Toxicol 33:244–259 CrossRefPubMedPubMedCentral
52.
Zurück zum Zitat Jia W, Meng X, Qian Z, Hua Z, Li T, Liu C (2016) Identification of three cannabimimetic indazole and pyrazole derivatives, APINACA 2 H-indazole analogue, AMPPPCA, and 5F-AMPPPCA. Drug Test Anal. doi: 10.​1002/​dta.​1967 Jia W, Meng X, Qian Z, Hua Z, Li T, Liu C (2016) Identification of three cannabimimetic indazole and pyrazole derivatives, APINACA 2 H-indazole analogue, AMPPPCA, and 5F-AMPPPCA. Drug Test Anal. doi: 10.​1002/​dta.​1967
53.
Zurück zum Zitat Choi H, Heo S, Choe S, Yang W, Park Y, Kim E, Chung H, Lee J (2013) Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS. Anal Bioanal Chem 405:3937–3944 CrossRefPubMed Choi H, Heo S, Choe S, Yang W, Park Y, Kim E, Chung H, Lee J (2013) Simultaneous analysis of synthetic cannabinoids in the materials seized during drug trafficking using GC-MS. Anal Bioanal Chem 405:3937–3944 CrossRefPubMed
54.
Zurück zum Zitat Banister SD, Wilkinson SM, Longworth M, Stuart J, Apetz N, English K, Brooker L, Goebel C, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M (2013) The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse. ACS Chem Neurosci 4:1081–1092 CrossRefPubMedPubMedCentral Banister SD, Wilkinson SM, Longworth M, Stuart J, Apetz N, English K, Brooker L, Goebel C, Hibbs DE, Glass M, Connor M, McGregor IS, Kassiou M (2013) The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse. ACS Chem Neurosci 4:1081–1092 CrossRefPubMedPubMedCentral
55.
Zurück zum Zitat Knapman A, Santiago M, Du YP, Bennallack PR, Christie MJ, Connor M (2013) A continuous, fluorescence-based assay of µ-opioid receptor activation in AtT-20 cells. J Biomol Screen 18:269–276 CrossRefPubMed Knapman A, Santiago M, Du YP, Bennallack PR, Christie MJ, Connor M (2013) A continuous, fluorescence-based assay of µ-opioid receptor activation in AtT-20 cells. J Biomol Screen 18:269–276 CrossRefPubMed
56.
Zurück zum Zitat Yet L (2009) Chapter 5.4: five-membered ring systems: with more than one N atom. In: Gordon WG, John AJ (eds) Progress in heterocyclic chemistry, vol 20. Elsevier, Amsterdam, pp 190–219 Yet L (2009) Chapter 5.4: five-membered ring systems: with more than one N atom. In: Gordon WG, John AJ (eds) Progress in heterocyclic chemistry, vol 20. Elsevier, Amsterdam, pp 190–219
57.
Zurück zum Zitat Hunt KW, Moreno DA, Suiter N, Clark CT, Kim G (2009) Selective synthesis of 1-functionalized-alkyl-1 H-indazoles. Org Lett 11:5054–5057 CrossRefPubMed Hunt KW, Moreno DA, Suiter N, Clark CT, Kim G (2009) Selective synthesis of 1-functionalized-alkyl-1 H-indazoles. Org Lett 11:5054–5057 CrossRefPubMed
58.
Zurück zum Zitat Saenz J, Mitchell M, Bahmanyar S, Stankovic N, Perry M, Craig-Woods B, Kline B, Yu S, Albizati K (2007) Process development and scale-up of AG035029. Org Process Res Dev 11:30–38 CrossRef Saenz J, Mitchell M, Bahmanyar S, Stankovic N, Perry M, Craig-Woods B, Kline B, Yu S, Albizati K (2007) Process development and scale-up of AG035029. Org Process Res Dev 11:30–38 CrossRef
59.
Zurück zum Zitat Grimsey NL, Graham ES, Dragunow M, Glass M (2010) Cannabinoid receptor 1 trafficking and the role of the intracellular pool: implications for therapeutics. Biochem Pharmacol 80:1050–1062 CrossRefPubMed Grimsey NL, Graham ES, Dragunow M, Glass M (2010) Cannabinoid receptor 1 trafficking and the role of the intracellular pool: implications for therapeutics. Biochem Pharmacol 80:1050–1062 CrossRefPubMed
Metadaten
Titel
The 2-alkyl-2H-indazole regioisomers of synthetic cannabinoids AB-CHMINACA, AB-FUBINACA, AB-PINACA, and 5F-AB-PINACA are possible manufacturing impurities with cannabimimetic activities
verfasst von
Mitchell Longworth
Samuel D. Banister
James B. C. Mack
Michelle Glass
Mark Connor
Michael Kassiou
Publikationsdatum
27.04.2016
Verlag
Springer Japan
Erschienen in
Forensic Toxicology / Ausgabe 2/2016
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-016-0316-y

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