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 Chemical Neuroscience

Volumn 6, Issue 9, 2015, Pages 1546-1559

  Banister, Samuel D ^a,b   Moir, Michael ^b   Stuart, Jordyn ^d   Kevin, Richard C ^c   Wood, Katie E ^c   Longworth, Mitchell ^b   Wilkinson, Shane M ^b   Beinat, Corinne ^a,b   Buchanan, Alexandra S ^a,e   Glass, Michelle ^f   Connor, Mark ^d   McGregor, Iain S ^c   Kassiou, Michael ^b,c  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

^d MACQUARIE UNIVERSITY   (Australia)

^e PRINCE OF WALES HOSPITAL   (Australia)

^f UNIVERSITY OF AUCKLAND   (New Zealand)

Author keywords

Cannabinoid; FUBINACA; JWH 018; PINACA; THC

Indexed keywords

3 (1 NAPHTHOYL) 1 PENTYLINDOLE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 5F AB PINACA; 5F ADB PINACA; 5F ADBICA; AB FUBINACA; AB PINACA; ADB FUBINACA; ADB PINACA; ADBICA; CANNABINOID; CANNABINOID 1 RECEPTOR; DESIGNER DRUG; DRONABINOL; INDAZOLE DERIVATIVE; INDOLE; UNCLASSIFIED DRUG; CANNABINOID 2 RECEPTOR; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; CNR1 PROTEIN, HUMAN; CNR2 PROTEIN, HUMAN; INDOLE DERIVATIVE;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BRADYCARDIA; CONTROLLED STUDY; DOSE RESPONSE; DRUG ACTIVITY; DRUG POTENCY; DRUG SYNTHESIS; FLUOROMETRY; HYPOTHERMIA; IN VIVO STUDY; INDUCED HYPOTHERMIA; MEMBRANE POTENTIAL; NONHUMAN; PRIORITY JOURNAL; RAT; TELEMETRY; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; BODY TEMPERATURE; CHEMICAL STRUCTURE; CHEMISTRY; COHORT ANALYSIS; DRUG EFFECTS; GENETICS; HEART RATE; HUMAN; MALE; METABOLISM; MOUSE; PRECLINICAL STUDY; SYNTHESIS; TUMOR CELL LINE; WISTAR RAT;

ANIMALS; BODY TEMPERATURE; CANNABINOID RECEPTOR AGONISTS; CANNABINOID RECEPTOR ANTAGONISTS; CELL LINE, TUMOR; COHORT STUDIES; DESIGNER DRUGS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG EVALUATION, PRECLINICAL; HEART RATE; HUMANS; INDAZOLES; INDOLES; MALE; MEMBRANE POTENTIALS; MICE; MOLECULAR STRUCTURE; RATS, WISTAR; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2;

EID: 84941765285     PISSN: None     EISSN: 19487193     Source Type: Journal    
DOI: 10.1021/acschemneuro.5b00112     Document Type: Article

References (42)

1. (2015) New Psychoactive Substances in Europe: An Update from the EU Early Warning System, European Monitoring Centre for Drugs and Drug Addiction, Luxembourg.
2. Huestis, M. A., Gorelick, D. A., Heishman, S. J., Preston, K. L., Nelson, R. A., Moolchan, E. T., and Frank, R. A. (2001) Blockade of effects of smoked marijuana by the CB1-selective cannabinoid receptor antagonist SR141716 Arch. Gen. Psychiatry 58, 322-328 10.1001/archpsyc.58.4.322
3. Howlett, A. C., Barth, F., Bonner, T. I., Cabral, G., Casellas, P., Devane, W. A., Felder, C. C., Herkenham, M., Mackie, K., Martin, B. R., Mechoulam, R., and Pertwee, R. G. (2002) International Union of Pharmacology. XXVII. Classification of cannabinoid receptors Pharmacol. Rev. 54, 161-202 10.1124/pr.54.2.161
4. Pertwee, R. G., Howlett, A. C., Abood, M. E., Alexander, S. P. H., Di Marzo, V., Elphick, M. R., Greasley, P. J., Hansen, H. S., Kunos, G., Mackie, K., Mechoulam, R., and Ross, R. A. (2010) International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: Beyond CB1 and CB2 Pharmacol. Rev. 62, 588-631 10.1124/pr.110.003004
5. Weissman, A., Milne, G. M., and Melvin, L. S. (1982) Cannabimimetic activity from CP-47,497, a derivative of 3-phenylcyclohexanol J. Pharmacol. Exp. Ther. 223, 516-523
6. Wiley, J. L., Barrett, R. L., Lowe, J., Balster, R. L., and Martin, B. R. (1995) Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats Neuropharmacology 34, 669-676 10.1016/0028-3908(95)00027-4
7. Auwärter, V., Dresen, S., Weinmann, W., Muller, M., Putz, M., and Ferreiros, N. (2009) 'Spice' and other herbal blends: harmless incense or cannabinoid designer drugs? J. Mass Spectrom. 44, 832-837 10.1002/jms.1558
8. Seely, K. A., Patton, A. L., Moran, C. L., Womack, M. L., Prather, P. L., Fantegrossi, W. E., Radominska-Pandya, A., Endres, G. W., Channell, K. B., Smith, N. H., McCain, K. R., James, L. P., and Moran, J. H. (2013) Forensic investigation of K2, Spice, and "bath salt" commercial preparations: a three-year study of new designer drug products containing synthetic cannabinoid, stimulant, and hallucinogenic compounds Forensic Sci. Int. 233, 416-422 10.1016/j.forsciint.2013.10.002
9. Zuba, D. and Byrska, B. (2013) Analysis of the prevalence and coexistence of synthetic cannabinoids in "herbal high" products in Poland Forensic Toxicol. 31, 21-30 10.1007/s11419-012-0159-0
10. Chung, H., Choi, H., Heo, S., Kim, E., and Lee, J. (2014) Synthetic cannabinoids abused in South Korea: drug identifications by the National Forensic Service from 2009 to June 2013 Forensic Toxicol. 32, 82-88 10.1007/s11419-013-0213-6
11. Langer, N., Lindigkeit, R., Schiebel, H. M., Ernst, L., and Beuerle, T. (2014) Identification and quantification of synthetic cannabinoids in 'spice-like' herbal mixtures: a snapshot of the German situation in the autumn of 2012 Drug Test. Anal. 6, 59-71 10.1002/dta.1499
12. Uchiyama, N., Kawamura, M., Kikura-Hanajiri, R., and Goda, Y. (2012) Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products Forensic Toxicol. 30, 114-125 10.1007/s11419-012-0136-7
13. Wilkinson, S. M., Banister, S. D., and Kassiou, M. (2015) Bioisosteric Fluorine in the Clandestine Design of Synthetic Cannabinoids Aust. J. Chem. 68, 4-8 10.1071/CH14198
14. Banister, S. D., Stuart, J., Kevin, R. C., Edington, A., Longworth, M., Wilkinson, S. M., Beinat, C., Buchanan, A. S., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., and Kassiou, M. (2015) Effects of Bioisosteric Fluorine in Synthetic Cannabinoid Designer Drugs JWH-018, AM-2201, UR-144, XLR-11, PB-22, 5F-PB-22, APICA, and STS-135 ACS Chem. Neurosci. 10.1021/acschemneuro.5b00107
15. Uchiyama, N., Matsuda, S., Wakana, D., Kikura-Hanajiri, R., and Goda, Y. (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal products Forensic Toxicol. 31, 93-100 10.1007/s11419-012-0171-4
16. Uchiyama, N., Matsuda, S., Kawamura, M., Kikura-Hanajiri, R., and Goda, Y. (2013) Two new-type cannabimimetic quinolinyl carboxylates, QUPIC and QUCHIC, two new cannabimimetic carboxamide derivatives, ADB-FUBINACA and ADBICA, and five synthetic cannabinoids detected with a thiophene derivative α-PVT and an opioid receptor agonist AH-7921 identified in illegal products Forensic Toxicol. 31, 223-240 10.1007/s11419-013-0182-9
17. Buchler, I. P., Hayes, M. J., Hedge, S. G., Hockerman, S. L., Jones, D. E., Kortum, S. W., Rico, J. G., Tenbrink, R. E., and Wu, K. K. (2009) Indazole derivatives as CB1 receptor modulators and their preparation and use in the treatment of CB1-mediated diseases. Patent WO 2009/106982.
18. 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
19. 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
20. Monte, A. A., Bronstein, A. C., Cao, D. J., Heard, K. J., Hoppe, J. A., Hoyte, C. O., Iwanicki, J. L., and Lavonas, E. J. (2014) An outbreak of exposure to a novel synthetic cannabinoid N. Engl. J. Med. 370, 389-90 10.1056/NEJMc1313655
21. Schwartz, M. D., Trecki, J., Edison, L. A., Steck, A. R., Arnold, J. K., and Gerona, R. R. (2015) A Common Source Outbreak of Severe Delirium Associated with Exposure to the Novel Synthetic Cannabinoid ADB-PINACA J. Emerg. Med. 48, 573-580 10.1016/j.jemermed.2014.12.038
22. Uchiyama, N., Shimokawa, Y., Kawamura, M., Kikura-Hanajiri, R., and 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 10.1007/s11419-014-0238-5
23. Wurita, A., Hasegawa, K., Minakata, K., Gonmori, K., Nozawa, H., Yamagishi, I., Watanabe, K., and Suzuki, O. (2015) Identification and quantitation of 5-fluoro-ADB-PINACA and MAB-CHMINACA in dubious herbal products Forensic Toxicol. 10.1007/s11419-015-0264-y
24. (2014) EMCDDA-Europol 2013 Annual Report on the implementation of Council Decision 2005/387/JHA, Implementation reports, European Monitoring Centre for Drugs and Drug Addiction, Luxembourg.
25. Takayama, T., Suzuki, M., Todoroki, K., Inoue, K., Min, J. Z., Kikura-Hanajiri, R., Goda, Y., and 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 alpha-PVT, by human liver microsome Biomed. Chromatogr. 28, 831-838 10.1002/bmc.3155
26. Thomsen, R., Nielsen, L. M., Holm, N. B., Rasmussen, H. B., and Linnet, K. (2014) Synthetic cannabimimetic agents metabolized by carboxylesterases Drug Test. Anal. 10.1002/dta.1731
27. Wohlfarth, A., Castaneto, M. S., Zhu, M., Pang, S., Scheidweiler, K. B., Kronstrand, R., and Huestis, M. A. (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 10.1208/s12248-015-9721-0
28. Castaneto, M. S., Wohlfarth, A., Pang, S., Zhu, M., Scheidweiler, K. B., Kronstrand, R., and Huestis, M. A. (2015) Identification of AB-FUBINACA metabolites in human hepatocytes and urine using high-resolution mass spectrometry Forensic Toxicol. 10.1007/s11419-015-0275-8
29. Liang, G., Choi-Sledeski, Y. M., Poli, G., Chen, X., Shum, P., Minnich, A., Wang, Q., Tsay, J., Sides, K., Cairns, J., Stoklosa, G., Nieduzak, T., Zhao, Z., Wang, J., and Vaz, R. J. (2010) A conformationally constrained inhibitor with an enhanced potency for β-tryptase and stability against semicarbazide-sensitive amine oxidase (SSAO) Bioorg. Med. Chem. Lett. 20, 6721-6724 10.1016/j.bmcl.2010.08.141
30. Wiley, J. L., Compton, D. R., Dai, D., Lainton, J. A. H., Phillips, M., Huffman, J. W., and Martin, B. R. (1998) Structure-activity relationships of indole- and pyrrole-derived cannabinoids J. Pharmacol. Exp. Ther. 285, 995-1004
31. Wiley, J. L., Marusich, J. A., and Huffman, J. W. (2014) Moving around the molecule: Relationship between chemical structure and in vivo activity of synthetic cannabinoids Life Sci. 97, 55-63 10.1016/j.lfs.2013.09.011
32. Wiley, J. L., Lefever, T. W., Cortes, R. A., and Marusich, J. A. (2014) Cross-substitution of Delta-tetrahydrocannabinol and JWH-018 in drug discrimination in rats Pharmacol., Biochem. Behav. 124, 123-128 10.1016/j.pbb.2014.05.016
33. Hine, B., Torrelio, M., and Gershon, S. (1977) Analgesic, Heart Rate, and Temperature Effects of Delta8-THC during Acute and Chronic Administration to Conscious Rats Pharmacology 15, 65-72 10.1159/000136664
34. Wiley, J. L., Marusich, J. A., Martin, B. R., and Huffman, J. W. (2012) 1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice Drug Alcohol Depend. 123, 148-153 10.1016/j.drugalcdep.2011.11.001
35. Wiley, J. L., Marusich, J. A., Lefever, T. W., Grabenauer, M., Moore, K. N., and Thomas, B. F. (2013) Cannabinoids in disguise: Delta9-tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles Neuropharmacology 75, 145-154 10.1016/j.neuropharm.2013.07.022
36. Banister, S. D., Wilkinson, S. M., Longworth, M., Stuart, J., Apetz, N., English, K., Brooker, L., Goebel, C., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., and Kassiou, M. (2013) The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse ACS Chem. Neurosci. 4, 1081-1092 10.1021/cn400035r
37. Rinaldi-Carmona, M., Barth, F., Heaulme, M., Shire, D., Calandra, B., Congy, C., Martinez, S., Maruani, J., Neliat, G., Caput, D., Ferrara, P., Soubrié, P., Brelière, J. C., and Le Fura, G. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor FEBS Lett. 350, 240-244 10.1016/0014-5793(94)00773-X
38. Rinaldi-Carmona, M., Barth, F., Heaulme, M., Alonso, R., Shire, D., Congy, C., Soubrié, P., Brelière, J. C., and Le Fur, G. (1995) Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist Life Sci. 56, 1941-1947 10.1016/0024-3205(95)00174-5
39. Rinaldi-Carmona, M., Barth, F., Millan, J., Derocq, J. M., Casellas, P., Congy, C., Oustric, D., Sarran, M., Bouaboula, M., Calandra, B., Portier, M., Shire, D., Brelière, J. C., and Le Fur, G. L. (1998) SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor J. Pharmacol. Exp. Ther. 284, 644-650
40. Portier, M., Rinaldi-Carmona, M., Pecceu, F., Combes, T., Poinot-Chazel, C., Calandra, B., Barth, F., le Fur, G., and Casellas, P. (1999) SR 144528, an antagonist for the peripheral cannabinoid receptor that behaves as an inverse agonist J. Pharmacol. Exp. Ther. 288, 582-589
41. Banister, S. D., Stuart, J., Conroy, T., Longworth, M., Manohar, M., Beinat, C., Wilkinson, S. M., Kevin, R. C., Hibbs, D. E., Glass, M., Connor, M., McGregor, I. S., and Kassiou, M. (2015) Structure-activity relationships of synthetic cannabinoid designer drug RCS-4 and its regioisomers and C4 homologues Forensic Toxicol. 10.1007/s11419-015-0282-9
42. Knapman, A., Santiago, M., Du, Y. P., Bennallack, P. R., Christie, M. J., and Connor, M. (2013) A continuous, fluorescence-based assay of μ-opioid receptor activation in AtT-20 cells J. Biomol. Screening 18, 269-276 10.1177/1087057112461376