Pharmacological characterization of emerging synthetic cannabinoids in HEK293T cells and hippocampal neurons

European Journal of Pharmacology

Volumn 786, Issue , 2016, Pages 234-245

  Costain, Willard J ^a   Tauskela, Joseph S ^a   Rasquinha, Ingrid ^a   Comas, Tanya ^a   Hewitt, Melissa ^a   Marleau, Vincent ^b   Soo, Evelyn C ^b  

^a NATIONAL RESEARCH COUNCIL CANADA   (Canada)

^b Environmental Health Center   (Canada)

Author keywords

5F PB 22 (PubChem CID: 72710774); AB PINACA (PubChem CID: 71301472); AKB 48 (PubChem CID: 57404063); AKB48 N (5FP) (PubChem CID: 71711119); Calcium; cAMP; Cannabinoid receptor; EAM 2201 (PubChem CID: 71308187); HEK293; JWH 250 (PubChem CID: 44397540); MAM 2201 (PubChem CID: 66570720); Neurons; PB 22 (PubChem CID: 71604304); STS 135 (PubChem CID: 57404059); Synthetic cannabinoid; XLR 11 (PubChem CID: 57501498)

Indexed keywords

(4 ETHYL 1 NAPHTHALENYL)[1 (5 FLUOROPENTYL) 1H INDOL 3 YL]METHANONE; 1 (1 PENTYL 1H INDOL 3 YL) 2 (2 METHOXYPHENYL)ETHANONE; 1 (5 FLUOROPENTYL) 8 QUINOLINYL ESTER 1H INDOLE 3 CARBOXYLIC ACID; 1 (5 FLUOROPENTYL) N TRICYCLO[3.3.1.13,7]DEC 1 YL 1H INDAZOLE 3 CARBOXAMIDE; 1 BUTYL 3 (1 NAPHTHOYL)INDOLE; 1 PENTYL 8 QUINOLINYL ESTER 1H INDOLE 3 CARBOXYLIC ACID; 1 PENTYL N TRICYCLO[3.3.1.13,7]DEC 1 YL 1H INDAZOLE 3 CARBOXAMIDE; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 3 (1 NAPHTHOYL) 1 PENTYLINDOLE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 5 (4 CHLORO 3 METHYLPHENYL) 1 (4 METHYLBENZYL) N (1,3,3 TRIMETHYLBICYCLO[2.2.1]HEPTAN 2 YL) 3 PYRAZOLECARBOXAMIDE; CANNABINOID DERIVATIVE; CYCLIC AMP; DEXANABINOL; EMERGING SYNTHETIC CANNABINOID; N (1 AMINO 3 METHYL 1 OXOBUTAN 2 YL) 1 PENTYL 1H INDAZOLE 3 CARBOXAMIDE; N (ADAMANTAN 1 YL) 1 (5 FLUOROPENTYL) 1H INDAZOLE 3 CARBOXAMIDE; RIMONABANT; UNCLASSIFIED DRUG; [1 (5 FLUOROPENTYL) 1H INDOL 3 YL](2,2,3,3 TETRAMETHYLCYCLOPROPYL)METHANONE; [1 (5 FLUOROPENTYL) 1H INDOL 3 YL](4 METHYL 1 NAPHTHALENYL)METHANONE; CANNABINOID;

ANALYSIS OF VARIANCE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG DETERMINATION; DRUG EFFICACY; DRUG POTENCY; EC50; ENDOCYTOSIS; ENZYME INHIBITION; GENETIC TRANSFECTION; HIPPOCAMPUS; HUMAN; HUMAN CELL; INTERNALIZATION; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION; ANIMAL; CELL SURVIVAL; CYTOLOGY; DRUG EFFECTS; FEMALE; HEK293 CELL LINE; PREGNANCY; SPRAGUE DAWLEY RAT; SYNTHESIS;

ANIMALS; CANNABINOIDS; CELL SURVIVAL; FEMALE; HEK293 CELLS; HIPPOCAMPUS; HUMANS; NEURONS; PREGNANCY; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84975452177     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2016.05.040     Document Type: Article

References (52)

1. 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., Kassiou, M., The synthesis and pharmacological evaluation of adamantane-derived indoles: cannabimimetic drugs of abuse. ACS Chem. Neurosci. 4 (2013), 1081–1092, 10.1021/cn400035r.
2. Banister, S.D., Moir, M., Stuart, J., Kevin, R.C., Wood, K.E., Longworth, M., Wilkinson, S.M., Beinat, C., Buchanan, A.S., Glass, M., Connor, M., McGregor, I.S., Kassiou, M., 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 (2015), 1546–1559, 10.1021/acschemneuro.5b00112.
3. 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., Kassiou, M., 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. 6 (2015), 1445–1458, 10.1021/acschemneuro.5b00107.
4. Bauer, M., Chicca, A., Tamborrini, M., Eisen, D., Lerner, R., Lutz, B., Poetz, O., Pluschke, G., Gertsch, J., Identification and quantification of a new family of peptide endocannabinoids (Pepcans) showing negative allosteric modulation at CB1 receptors. J. Biol. Chem. 287 (2012), 36944–36967, 10.1074/jbc.M112.382481.
5. Blair, R.E., Deshpande, L.S., Sombati, S., Falenski, K.W., Martin, B.R., DeLorenzo, R.J., Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus. J. Pharmacol. Exp. Ther. 317 (2006), 1072–1078, 10.1124/jpet.105.100354.
6. Bosier, B., Muccioli, G.G., Hermans, E., Lambert, D.M., Functionally selective cannabinoid receptor signalling: therapeutic implications and opportunities. Biochem Pharmacol. 80 (2010), 1–12, 10.1016/j.bcp.2010.02.013.
7. Breivogel, C.S., Sim, L.J., Childers, S.R., Regional differences in cannabinoid receptor/G-protein coupling in rat brain. J. Pharmacol. Exp. Ther. 282 (1997), 1632–1642.
8. Breivogel, C.S., Selley, D.E., Childers, S.R., Cannabinoid receptor agonist efficacy for stimulating [35S]GTPgammaS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity. J. Biol. Chem. 273 (1998), 16865–16873.
9. Brents, L.K., Gallus-Zawada, A., Radominska-Pandya, A., Vasiljevik, T., Prisinzano, T.E., Fantegrossi, W.E., Moran, J.H., Prather, P.L., Monohydroxylated metabolites of the K2 synthetic cannabinoid JWH-073 retain intermediate to high cannabinoid 1 receptor (CB1R) affinity and exhibit neutral antagonist to partial agonist activity. Biochem. Pharmacol. 83 (2012), 952–961.
10. Buchler, I.P., Hayes, M.J., Hegde, S.G., Hockerman, S.L., Jones, D.E., Kortum, S.W., Rico, J.G., TenBrink, R.E., Wu, K.K., 2011. Indazole derivatives. US 12/918,914.
11. De Luca, M.A., Castelli, M.P., Loi, B., Porcu, A., Martorelli, M., Miliano, C., Kellett, K., Davidson, C., Stair, J.L., Schifano, F., Di Chiara, G., Native CB1 receptor affinity, intrinsic activity and accumbens shell dopamine stimulant properties of third generation SPICE/K2 cannabinoids: BB-22, 5F-PB-22, 5F-AKB-48 and STS-135. Neuropharmacology 105 (2015), 630–638, 10.1016/j.neuropharm.2015.11.017.
12. Deshpande, L.S., Blair, R.E., Ziobro, J.M., Sombati, S., Martin, B.R., DeLorenzo, R.J., Endocannabinoids block status epilepticus in cultured hippocampal neurons. Eur. J. Pharmacol. 558 (2007), 52–59, 10.1016/j.ejphar.2006.11.030.
13. EMCDDA, 2012. EMCDDA | 2012 Annual Report on the State of the Drugs Problem in Europe. Lisbon. 〈 http://dx.doi.org/10.2810/64775〉.
14. EMCDDA, 2014. EMCDDA | Perspectives on Drugs: Synthetic Cannabinoids in Europe [WWW Document]. (URL) 〈http://www.emcdda.europa.eu/topics/pods/synthetic-cannabinoids#panel2〉 (accessed 22.10.14).
15. Felder, C., Joyce, K., Briley, E., Mansouri, J., Mackie, K., Blond, O., Lai, Y., Ma, A., Mitchell, R., Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol. Pharmacol. 48 (1995), 443–450.
16. Glass, M., Northup, J.K., Agonist selective regulation of G proteins by cannabinoid CB) (1) (and CB) (2) (receptors). Mol. Pharmacol. 56 (1999), 1362–1369.
17. Govaerts, S.J., Hermans, E., Lambert, D.M., Comparison of cannabinoid ligands affinities and efficacies in murine tissues and in transfected cells expressing human recombinant cannabinoid receptors. Eur. J. Pharm. Sci. 23 (2004), 233–243, 10.1016/j.ejps.2004.07.013.
18. Houston, D.B., Howlett, A.C., Differential receptor-G-protein coupling evoked by dissimilar cannabinoid receptor agonists. Cell Signal. 10 (1998), 667–674.
19. Howlett, A.C., Mukhopadhyay, S., Cellular signal transduction by anandamide and 2-arachidonoylglycerol. Chem. Phys. Lipids 108 (2000), 53–70.
20. Howlett, A.C., Breivogel, C.S., Childers, S.R., Deadwyler, S.A., Hampson, R.E., Porrino, L.J., Cannabinoid physiology and pharmacology: 30 years of progress. Neuropharmacology, 47(Suppl 1), 2004, 10.1016/j.neuropharm.2004.07.030.
21. 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., Pertwee, R.G., International Union of Pharmacology. XXVII. Classification of cannabinoid receptors. Pharmacol. Rev. 54 (2002), 161–202.
22. Irannejad, R., Tomshine, J.C., Tomshine, J.R., Chevalier, M., Mahoney, J.P., Steyaert, J., Rasmussen, S.G.F., Sunahara, R.K., El-Samad, H., Huang, B., von Zastrow, M., Conformational biosensors reveal GPCR signalling from endosomes. Nature 495 (2013), 534–538, 10.1038/nature12000.
23. Irie, T., Kikura-Hanajiri, R., Usami, M., Uchiyama, N., Goda, Y., Sekino, Y., MAM-2201, a synthetic cannabinoid drug of abuse, suppresses the synaptic input to cerebellar Purkinje cells via activation of presynaptic CB1 receptors. Neuropharmacology 95 (2015), 479–491, 10.1016/j.neuropharm.2015.02.025.
24. Kearn, C.S., Greenberg, M.J., DiCamelli, R., Kurzawa, K., Hillard, C.J., Relationships between ligand affinities for the cerebellar cannabinoid receptor CB1 and the induction of GDP/GTP exchange. J. Neurochem 72 (1999), 2379–2387.
25. Kenakin, T., Functional selectivity through protean and biased agonism: who steers the ship?. Mol. Pharmacol. 72 (2007), 1393–1401, 10.1124/mol.107.040352.
26. Landsman, R.S., Burkey, T.H., Consroe, P., Roeske, W.R., Yamamura, H.I., SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur. J. Pharmacol. 334 (1997), R1–R2.
27. Laprairie, R.B., Bagher, A.M., Kelly, M.E.M., Dupré, D.J., Denovan-Wright, E.M., Type 1 cannabinoid receptor ligands display functional selectivity in a cell culture model of striatal medium spiny projection neurons. J. Biol. Chem. 289 (2014), 24845–24862, 10.1074/jbc.M114.557025.
28. Lauckner, J.E., Hille, B., Mackie, K., The cannabinoid agonist WIN55,212–2 increases intracellular calcium via CB1 receptor coupling to Gq/11 G proteins. Proc. Natl. Acad. Sci. USA 102 (2005), 19144–19149, 10.1073/pnas.0509588102.
29. Leterrier, C., Bonnard, D., Carrel, D., Rossier, J., Lenkei, Z., Constitutive endocytic cycle of the CB1 cannabinoid receptor. J. Biol. Chem. 279 (2004), 36013–36021, 10.1074/jbc.M403990200.
30. McAllister, S.D., Griffin, G., Satin, L.S., Abood, M.E., Cannabinoid receptors can activate and inhibit G protein-coupled inwardly rectifying potassium channels in a xenopus oocyte expression system. J. Pharmacol. Exp. Ther. 291 (1999), 618–626.
31. McPartland, J.M., Glass, M., Pertwee, R.G., Meta-analysis of cannabinoid ligand binding affinity and receptor distribution: interspecies differences. Br. J. Pharmacol. 152 (2007), 583–593, 10.1038/sj.bjp.0707399.
32. Morena, M., Roozendaal, B., Trezza, V., Ratano, P., Peloso, A., Hauer, D., Atsak, P., Trabace, L., Cuomo, V., McGaugh, J.L., Schelling, G., Campolongo, P., Endogenous cannabinoid release within prefrontal-limbic pathways affects memory consolidation of emotional training. Proc. Natl. Acad. Sci. USA 111 (2014), 18333–18338, 10.1073/pnas.1420285111.
33. Mukhopadhyay, S., Howlett, A.C., Chemically distinct ligands promote differential CB1 cannabinoid receptor-Gi protein interactions. Mol. Pharmacol. 67 (2005), 2016–2024, 10.1124/mol.104.003558.
34. Németh, B., Ledent, C., Freund, T.F., Hájos, N., CB1 receptor-dependent and -independent inhibition of excitatory postsynaptic currents in the hippocampus by WIN 55,212-2. Neuropharmacology 54 (2008), 51–57, 10.1016/j.neuropharm.2007.07.003.
35. Niehaus, J.L., Liu, Y., Wallis, K.T., Egertová, M., Bhartur, S.G., Mukhopadhyay, S., Shi, S., He, H., Selley, D.E., Howlett, A.C., Elphick, M.R., Lewis, D.L., CB1 cannabinoid receptor activity is modulated by the cannabinoid receptor interacting protein CRIP 1a. Mol. Pharmacol. 72 (2007), 1557–1566, 10.1124/mol.107.039263.
36. Pacico, N., Mingorance-Le Meur, A., New in vitro phenotypic assay for epilepsy: fluorescent measurement of synchronized neuronal calcium oscillations. PLoS One, 9, 2014, e84755, 10.1371/journal.pone.0084755.
37. Pertwee, R.G., Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol. Ther. 74 (1997), 129–180.
38. Ramírez-Franco, J., Bartolomé-Martín, D., Alonso, B., Torres, M., Sánchez-Prieto, J., Cannabinoid type 1 receptors transiently silence glutamatergic nerve terminals of cultured cerebellar granule cells. PLoS One, 9, 2014, e88594, 10.1371/journal.pone.0088594.
39. Shen, M., Thayer, S.A., Cannabinoid receptor agonists protect cultured rat hippocampal neurons from excitotoxicity. Mol. Pharmacol. 54 (1998), 459–462.
40. Shen, M., Thayer, S.A., The cannabinoid agonist Win55,212-2 inhibits calcium channels by receptor-mediated and direct pathways in cultured rat hippocampal neurons. Brain Res. 783 (1998), 77–84.
41. Shen, M., Thayer, S.A., Delta9-tetrahydrocannabinol acts as a partial agonist to modulate glutamatergic synaptic transmission between rat hippocampal neurons in culture. Mol. Pharmacol. 55 (1999), 8–13.
42. Shen, M., Piser, T.M., Seybold, V.S., Thayer, S.A., Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures. J. Neurosci. 16 (1996), 4322–4334.
43. Sugiura, T., Kodaka, T., Nakane, S., Miyashita, T., Kondo, S., Suhara, Y., Takayama, H., Waku, K., Seki, C., Baba, N., Ishima, Y., Evidence that the cannabinoid CB1 receptor Is a 2-arachidonoylglycerol receptor: structure-activity relationship of 2-arachidonoylglycerol, ether-linked analogues, and related compounds. J. Biol. Chem. 274 (1999), 2794–2801, 10.1074/jbc.274.5.2794.
44. Tauskela, J.S., Comas, T., Hewitt, M., Aylsworth, A., Zhao, X., Martina, M., Costain, W.J., Effect of synthetic cannabinoids on spontaneous neuronal activity: Evaluation using Ca2+spiking and multi-electrode arrays. Eur. J. Pharmacol, 2016, 10.1016/j.ejphar.2016.05.038.
45. Twitchell, W., Brown, S., Mackie, K., Cannabinoids inhibit N- and P/Q-type calcium channels in cultured rat hippocampal neurons. J. Neurophysiol. 78 (1997), 43–50.
46. Uchiyama, N., Kikura-Hanajiri, R., Goda, Y., Identification of a novel cannabimimetic phenylacetylindole, cannabipiperidiethanone, as a designer drug in a herbal product and its affinity for cannabinoid CB1 and CB2 receptors. Chem. Pharm. Bull. 59 (2011), 1203–1205.
47. Uchiyama, N., Kawamura, M., Kikura-Hanajiri, R., Goda, Y., URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products. Forensic Sci. Int. 227 (2013), 21–32, 10.1016/j.forsciint.2012.08.047.
48. United Nations, 1972. Single Convention on Narcotic Drugs, 1961. Geneva.
49. WHO, 2015. WHO Expert Committee on Drug Dependence - 36th Report. WHO Tech. Rep. Ser. 991, pp. 1–50.
50. Wiley, J.L., Marusich, J.A., Martin, B.R., Huffman, J.W., 1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice. Drug Alcohol Depend. 123 (2012), 148–153.
51. Wiley, J.L., Marusich, J.A., Lefever, T.W., Grabenauer, M., Moore, K.N., Thomas, B.F., Cannabinoids in disguise: Δ9-Tetrahydrocannabinol-like effects of tetramethylcyclopropyl ketone indoles. Neuropharmacology 75 (2013), 145–154.
52. Wu, D.-F., Yang, L.-Q., Goschke, A., Stumm, R., Brandenburg, L.-O., Liang, Y.-J., Höllt, V., Koch, T., Role of receptor internalization in the agonist-induced desensitization of cannabinoid type 1 receptors. J. Neurochem. 104 (2008), 1132–1143, 10.1111/j.1471-4159.2007.05063.x.