Moving around the molecule: Relationship between chemical structure and in vivo activity of synthetic cannabinoids

Life Sciences

Volumn 97, Issue 1, 2014, Pages 55-63

  Wiley, Jenny L ^a   Marusich, Julie A ^a   Huffman, John W ^b  

^a RTI INTERNATIONAL   (United States)

^b CLEMSON UNIVERSITY   (United States)

Author keywords

Alkylindoles; Aromatic stacking; Cannabinoids; Herbal marijuana; Indoles; JWH 018; Pyrroles; Review; Spice; Synthetic cannabinoids

Indexed keywords

ALKYLINDOLES; AROMATIC STACKING; CANNABINOIDS; HERBAL MARIJUANA; INDOLES; JWH-018; PYRROLES; REVIEW; SPICE; SYNTHETIC CANNABINOIDS;

ANIMALS; BENZOXAZINES; CANNABINOIDS; DESIGNER DRUGS; HUMANS; INDOLES; MICE; MORPHOLINES; NAPHTHALENES; PYRROLES; RECEPTOR, CANNABINOID, CB1; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84894039860     PISSN: 00243205     EISSN: 18790631     Source Type: Journal    
DOI: 10.1016/j.lfs.2013.09.011     Document Type: Review

References (55)

1. M.M. Aung, G. Griffin, J.W. Huffman, M. Wu, C. Keel, B. Yang, V.M. Showalter, M.E. Abood, and B.R. Martin Influence of the N-1 alkyl chain length of cannabimimetic indoles upon CB(1) and CB(2) receptor binding Drug Alcohol Depend 60 2000 133 140 (Pubitemid 30625016)
2. C.S. Breivogel, and S.R. Childers Cannabinoid agonist signal transduction in rat brain: comparison of cannabinoid agonists in receptor binding, G-protein activation, and adenylyl cyclase inhibition J Pharmacol Exp Ther 295 2000 328 336
3. L.K. Brents, A. Gallus-Zawada, A. Radominska-Pandya, T. Vasiljevik, T.E. Prisinzano, W.E. Fantegrossi, J.H. Moran, and P.L. Prather 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
4. D.R. Compton, P.J. Little, B.R. Martin, J.W. Gilman, J.K. Saha, V.S. Jorapur, H.P. Sard, and R.K. Razdan Synthesis and pharmacological evaluation of amino, azido, and nitrogen mustard analogues of 10-substituted cannabidiol and 11- or 12-substituted delta 8-tetrahydrocannabinol J Med Chem 33 1990 1437 1443 (Pubitemid 20148382)
5. D.R. Compton, L.H. Gold, S.J. Ward, R.L. Balster, and B.R. Martin Aminoalkylindole analogs: cannabimimetic activity of a class of compounds structurally distinct from delta 9-tetrahydrocannabinol J Pharmacol Exp Ther 263 1992 1118 1126 (Pubitemid 23157189)
6. D.R. Compton, K.C. Rice, B.R. De Costa, R.K. Razdan, L.S. Melvin, M.R. Johnson, and B.R. Martin Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities J Pharmacol Exp Ther 265 1993 218 226 (Pubitemid 23320964)
7. D.R. Compton, M.D. Aceto, J. Lowe, and B.R. Martin In vivo characterization of a specific cannabinoid receptor antagonist (SR141716A): inhibition of delta 9-tetrahydrocannabinol-induced responses and apparent agonist activity J Pharmacol Exp Ther 277 1996 586 594 (Pubitemid 27168965)
8. A.O. Cox, R.C. Daw, M.D. Mason, M. Grabenauer, P.G. Pande, K.H. Davis, J.L. Wiley, P.R. Stout, B.F. Thomas, and J.W. Huffman Use of SPME-HS-GC-MS for the analysis of herbal products containing synthetic cannabinoids J Anal Toxicol 36 2012 293 302
9. R. Denooz, J.C. Vanheugen, M. Frederich, P. de Tullio, and C. Charlier Identification and structural elucidation of four cannabimimetic compounds (RCS-4, AM-2201, JWH-203 and JWH-210) in seized products J Anal Toxicol 37 2013 56 63
10. W.A. Devane, F.A. Dysarz, M.R. Johnson, L.S. Melvin, and A.C. Howlett Determination and characterization of a cannabinoid receptor in rat brain Mol Pharmacol 34 1988 605 613 (Pubitemid 19007296)
11. W.A. Devane, L. Hanus, A. Breuer, R.G. Pertwee, L.A. Stevenson, G. Griffin, D. Gibson, A. Mandelbaum, A. Etinger, and R. Mechoulam Isolation and structure of a brain constituent that binds to the cannabinoid receptor Science 258 1992 1946 1949 (Pubitemid 23026736)
12. A.K. Dutta, W. Ryan, B.F. Thomas, M. Singer, D.R. Compton, B.R. Martin, and R.K. Razdan Synthesis, pharmacology, and molecular modeling of novel 4-alkyloxy indole derivatives related to cannabimimetic aminoalkyl indoles (AAIs) Bioorg Med Chem 5 1997 1591 1600 (Pubitemid 27389341)
13. J.M. Frost, M.J. Dart, K.R. Tietje, T.R. Garrison, G.K. Grayson, A.V. Daza, O.F. El-Kouhen, L.N. Miller, L. Li, B.B. Yao, G.C. Hsieh, M. Pai, C.Z. Zhu, P. Chandran, and M.D. Meyer Indol-3-yl-tetramethylcyclopropyl ketones: effects of indole ring substitution on CB2 cannabinoid receptor activity J Med Chem 51 2008 1904 1912 (Pubitemid 351438872)
14. J.M. Frost, M.J. Dart, K.R. Tietje, T.R. Garrison, G.K. Grayson, A.V. Daza, O.F. El-Kouhen, B.B. Yao, G.C. Hsieh, M. Pai, C.Z. Zhu, P. Chandran, and M.D. Meyer Indol-3-ylcycloalkyl ketones: effects of N1 substituted indole side chain variations on CB(2) cannabinoid receptor activity J Med Chem 53 2010 295 315
15. Y. Gaoni, and R. Mechoulam Isolation, structure, and partial synthesis of an active constituent of hashish J Am Chem Soc 86 1964 1646 1647
16. B.C. Ginsburg, D.R. Schulze, L. Hruba, and L.R. McMahon JWH-018 and JWH-073: delta-tetrahydrocannabinol-like discriminative stimulus effects in monkeys J Pharmacol Exp Ther 340 2012 37 45
17. M. Grabenauer, W.L. Krol, J.L. Wiley, and B.F. Thomas Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: implications for nontargeted screening of designer drugs Anal Chem 84 2012 5574 5581
18. L. Hanus, S. Abu-Lafi, E. Fride, A. Breuer, Z. Vogel, D.E. Shalev, I. Kustanovich, and R. Mechoulam 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor Proc Natl Acad Sci U S A 98 2001 3662 3665 (Pubitemid 32249827)
19. D.R. Haubrich, S.J. Ward, E. Baizman, M.R. Bell, J. Bradford, R. Ferrari, M. Miller, M. Perrone, A.K. Pierson, and J.K. Saelens et al. Pharmacology of pravadoline: a new analgesic agent J Pharmacol Exp Ther 255 1990 511 522
20. J.W. Huffman Cannabimimetic indoles, pyrroles and indenes Curr Med Chem 6 1999 705 720 (Pubitemid 29399500)
21. J.W. Huffman Cannabimimetic indoles, pyrroles, and indenes: Structure-activity relationships and receptor interactions P.H. Reggio, The cannabinoid receptors 2009 Humana Press New York 49 94
22. J.W. Huffman, and L.W. Padgett Recent developments in the medicinal chemistry of cannabimimetic indoles, pyrroles and indenes Curr Med Chem 12 2005 1395 1411 (Pubitemid 40872583)
23. J.W. Huffman, D. Dai, B.R. Martin, and D.R. Compton Design, synthesis and pharmacology of cannabimimetic indoles Bioorg Med Chem Lett 4 1994 563 566 (Pubitemid 24131892)
24. J.W. Huffman, R. Mabon, M.J. Wu, J. Lu, R. Hart, D.P. Hurst, P.H. Reggio, J.L. Wiley, and B.R. Martin 3-Indolyl-1-naphthylmethanes: new cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB(1) cannabinoid receptor Bioorg Med Chem 11 2003 539 549 (Pubitemid 36132231)
25. J.W. Huffman, P.V. Szklennik, A. Almond, K. Bushell, D.E. Selley, H. He, M.P. Cassidy, J.L. Wiley, and B.R. Martin 1-Pentyl-3-phenylacetylindoles, a new class of cannabimimetic indoles Bioorg Med Chem Lett 15 2005 4110 4113 (Pubitemid 41132671)
26. J.W. Huffman, G. Zengin, M.J. Wu, J. Lu, G. Hynd, K. Bushell, A.L. Thompson, S. Bushell, C. Tartal, D.P. Hurst, P.H. Reggio, D.E. Selley, M.P. Cassidy, J.L. Wiley, and B.R. Martin Structure-activity relationships for 1-alkyl-3-(1-naphthoyl)indoles at the cannabinoid CB(1) and CB(2) receptors: steric and electronic effects of naphthoyl substituents. New highly selective CB(2) receptor agonists Bioorg Med Chem 13 2005 89 112 (Pubitemid 39575695)
27. J.W. Huffman, L.W. Padgett, M.L. Isherwood, J.L. Wiley, and B.R. Martin 1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: new high affinity ligands for the cannabinoid CB(1) and CB(2) receptors Bioorg Med Chem Lett 16 2006 5432 5435 (Pubitemid 44332197)
28. T.U. Järbe, H. Deng, S.K. Vadivel, and A. Makriyannis Cannabinergic aminoalkylindoles, including AM678 = JWH018 found in 'Spice', examined using drug (Delta9-tetrahydrocannabinol) discrimination for rats Behav Pharmacol 22 2011 498 507
29. P. Kavanagh, A. Grigoryev, S. Savchuk, I. Mikhura, and A. Formanovsky UR-144 in products sold via the Internet: identification of related compounds and characterization of pyrolysis products Drug Test Anal 2013 10.1002/dta.1456 [Epub ahead of print]
30. J.A.H. Lainton, J.W. Huffman, B.R. Martin, and D.R. Compton 1-Alkyl-3-(1-naphthoyl)pyrroles: a new cannabinoid class Tetrahedron Lett 36 1995 1401 1404
31. R. Lindigkeit, A. Boehme, I. Eiserloh, M. Luebbecke, M. Wiggermann, L. Ernst, and T. Beuerle Spice: a never ending story? Forensic Sci Int 191 2009 58 63
32. P.J. Little, D.R. Compton, M.R. Johnson, L.S. Melvin, and B.R. Martin Pharmacology and stereoselectivity of structurally novel cannabinoids in mice J Pharmacol Exp Ther 247 1988 1046 1051 (Pubitemid 19022114)
33. B.K. Logan, L.E. Reinhold, A. Xu, and F.X. Diamond Identification of synthetic cannabinoids in herbal incense blends in the United States J Forensic Sci 57 2012 1168 1180
34. C. Manera, T. Tuccinardi, and A. Martinelli Indoles and related compounds as cannabinoid ligands Mini Rev Med Chem 8 2008 370 387 (Pubitemid 351606778)
35. B.R. Martin, R.L. Balster, R.K. Razdan, L.S. Harris, and W.L. Dewey Behavioral comparisons of the stereoisomers of tetrahydrocannabinols Life Sci 29 1981 565 574 (Pubitemid 11030909)
36. B.R. Martin, D.R. Compton, B.F. Thomas, W.R. Prescott, P.J. Little, R.K. Razdan, M.R. Johnson, L.S. Melvin, R. Mechoulam, and S.J. Ward Behavioral, biochemical, and molecular modeling evaluations of cannabinoid analogs Pharmacol Biochem Behav 40 1991 471 478
37. L.A. Matsuda, S.J. Lolait, M.J. Brownstein, A.C. Young, and T.I. Bonner Structure of a cannabinoid receptor and functional expression of the cloned cDNA Nature 346 1990 561 564
38. R. Mechoulam, S. Ben-Shabat, L. Hanus, M. Ligumsky, N.E. Kaminski, A.R. Schatz, A. Gopher, S. Almog, B.R. Martin, and D.R. Compton et al. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors Biochem Pharmacol 50 1995 83 90
39. S. Munro, K.L. Thomas, and M. Abu-Shaar Molecular characterization of a peripheral receptor for cannabinoids Nature 365 1993 61 64
40. National Research Council Guide for the Care and Use of Laboratory Animals 1996 National Academy Press Washington, D.C
41. P.H. Reggio, S. Basu-Dutt, J. Barnett-Norris, M.T. Castro, D.P. Hurst, H.H. Seltzman, M.J. Roche, A.F. Gilliam, B.F. Thomas, L.A. Stevenson, R.G. Pertwee, and M.E. Abood The bioactive conformation of aminoalkylindoles at the cannabinoid CB1 and CB2 receptors: insights gained from (E)- and (Z)-naphthylidene indenes J Med Chem 41 1998 5177 5187 (Pubitemid 29016312)
42. M. Rinaldi-Carmona, F. Barth, M. Héaulme, D. Shire, B. Calandra, C. Congy, S. Martinez, J. Maruani, G. Néliat, D. Caput, P. Ferrara, P. Soubrié, J.C. Brelière, and G. Le Fur SR141716A, a potent and selective antagonist of the brain cannabinoid receptor FEBS Lett 350 1994 240 244 (Pubitemid 24268029)
43. M. Rinaldi-Carmona, F. Barth, J. Millan, J. Defrocq, P. Casellas, C. Congy, D. Oustric, M. Sarran, M. Bouaboula, B. Calandra, M. Portier, D. Shire, J. Breliere, and G. Le Fur SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor J Pharmacol Exp Ther 284 1998 644 650 (Pubitemid 28086654)
44. M.C. Sañudo-Peña, J. Romero, G.E. Seale, J.J. Fernandez-Ruiz, and J.M. Walker Activational role of cannabinoids on movement Eur J Pharmacol 391 2000 269 274 (Pubitemid 30154094)
45. V.M. Showalter, D.R. Compton, B.R. Martin, and M.E. Abood Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands J Pharmacol Exp Ther 278 1996 989 999 (Pubitemid 27166944)
46. B.F. Thomas, D.R. Compton, B.R. Martin, and S.F. Semus Modeling the cannabinoid receptor: a three-dimensional quantitative structure-activity analysis Mol Pharmacol 40 1991 656 665
47. N. Uchiyama, M. Kawamura, R. Kikura-Hanajiri, and Y. Goda URB-754: a new class of designer drug and 12 synthetic cannabinoids detected in illegal products Forensic Sci Int 227 2013 21 32
48. I. Vardakou, C. Pistos, and C. Spiliopoulou Spice drugs as a new trend: mode of action, identification and legislation Toxicol Lett 197 2010 157 162
49. J.M. Wiebelhaus, J.L. Poklis, A. Poklis, R.E. Vann, A.H. Lichtman, and L.E. Wise Inhalation exposure to smoke from synthetic "marijuana" produces potent cannabimimetic effects in mice Drug Alcohol Depend 126 2012 316 323
50. J.L. Wiley, and B.R. Martin Cannabinoid pharmacological properties common to other centrally acting drugs Eur J Pharmacol 471 2003 185 193 (Pubitemid 36776413)
51. J.L. Wiley, D.R. Compton, D. Dai, J.A. Lainton, M. Phillips, J.W. Huffman, and B.R. Martin Structure-activity relationships of indole- and pyrrole-derived cannabinoids J Pharmacol Exp Ther 285 1998 995 1004 (Pubitemid 28277896)
52. J.L. Wiley, R.L. Evans, D.B. Grainger, and K.L. Nicholson Age-dependent differences in sensitivity and sensitization to cannabinoids and 'club drugs' in male adolescent and adult rats Addict Biol 13 2008 277 286
53. J.L. Wiley, J.A. Marusich, B.R. Martin, and J.W. Huffman 1-Pentyl-3-phenylacetylindoles and JWH-018 share in vivo cannabinoid profiles in mice Drug Alcohol Depend 123 2012 148 153
54. J.L. Wiley, V.J. Smith, J. Chen, B.R. Martin, and J.W. Huffman Synthesis and pharmacology of 1-alkyl-3-(1-naphthoyl)indoles: steric and electronic effects of 4- and 8-halogenated naphthoyl substituents Bioorg Med Chem 20 2012 2067 2081
55. 9-Tetrahydrocannabinol- like effects of tetramethylcyclopropyl ketone indoles Neuropharmacology 75 2013 145 154