Cannabinoid receptors and their ligands: Ligand-ligand and ligand-receptor modeling approaches

Handbook of Experimental Pharmacology

Volumn 168, Issue , 2005, Pages 247-281

  Reggio, P H ^a  

^a UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

Author keywords

Cannabinoid SAR; Modeling; Receptor modeling

Indexed keywords

EID: 85099486303     PISSN: 01712004     EISSN: 18650325     Source Type: Book Series    
DOI: 10.1007/3-540-26573-2_8     Document Type: Article

References (137)

1. Abadji V, Lin S, Taha G, Griffin G, Stevenson LA, Pertwee RG, Makriyannis A (1994) (R)-Methanandamide: A chiral novel anandamide possessing higher potency and metabolic stability. J Med Chem 37:1889-1893
2. Abood ME, Ditto KE, Noel MA, Showalter VM, Tao Q (1997) Isolation and expression of a mouse CB1 cannabinoid receptor gene. Comparison of binding properties with those of native CB1 receptors in mouse brain and N18TG2 neuroblastoma cells. Biochem Pharmacol 53:207-214
3. Adams IB, Ryan W, Singer M, Razdan RK, Compton DR, Martin BR(1995a) Pharmacological and behavioral evaluation of alkylated anandamide analogs. Life Sci 56:2041-2048
4. Adams IB, Ryan W, Singer M, Thomas BF, Compton DR, Razdan RK, Martin BR(1995b) Evaluation of cannabinoid receptor binding and in vivo activities for anandamide analogs. J Pharmacol Exp Ther 273:1172-1181
5. Barnett-Norris J, Guarnieri F, Hurst DP, Reggio PH (1998) Exploration of biologically relevant conformations of anandamide, 2-Arachidonylglycerol, and their analogues using conformational memories. J Med Chem 41:4861-4872
6. Barnett-Norris J, Hurst DP, Buehner K, Ballesteros JA, Guarnieri F, Reggio PH (2002a) Agonist alkyl tail interaction with cannabinoid CB1 receptor V6.43/I646 groove induces a helix 6 active conformation. Int J Quantum Chem 88:76-86
7. Barnett-Norris J, Hurst DP, Lynch DL, Guarnieri F, Makriyannis A, Reggio PH (2002b) Conformational memories and the endocannabinoid binding site at the cannabinoid CB1 receptor. J Med Chem 45:3649-3659
8. Berglund BA, Boring DL, Wilken GH, Makriyannis A, Howlett AC, Lin S (1998) Structural requirements for arachidonylethanolamide interaction with CB1 and CB2 cannabinoid receptors: Pharmacology of the carbonyl and ethanolamide groups. Prostaglandins Leukot Essent Fatty Acids 59:111-118
9. Berglund BA, Boring DL, Howlett AC (1999) Investigation of structural analogs of prostaglandin amides for binding to and activation of CB1 and CB2 cannabinoid receptors in rat brain and human tonsils. Adv Exp Med Biol 469:527-533
10. Berglund BA, Fleming PR, Rice KC, Shim JY, Welsh WJ, Howlett AC (2000) Development of a novel class of monocyclic and bicyclic alkyl amides that exhibit CB1 and CB2 cannabinoid receptor affinity and receptor activation. Drug Des Discov 16:281-294
11. Bonechi C, Brizzi A, Brizzi V, Francoli M, Donati A, Rossi C (2001) Conformational analysis of N-Arachidonylethanolamide (anandamide) using nuclear magnetic R\resonanceand theoretical calculations. Magn Reson Chem 39:432-437
12. Bouaboula M, Perrachon S, Milligan L, Canat X, Rinaldi-Carmona M, Portier M, Barth F, Calandra B, Pecceu F, Lupker J, Maffrand JP, Le Fur G, Casellas P (1997) A selective inverse agonist for central cannabinoid receptor inhibits mitogen-Activated protein kinase activation stimulated by insulin or insulin-like growth factor 1. Evidence for a new model of receptor/ligand interactions. J Biol Chem 272:22330-22339
13. Bouaboula M, Desnoyer N, Carayon P, Combes T, Casellas P (1999) Gi protein modulation induced by a selective inverse agonist for the peripheral cannabinoid receptor CB2: Implication for intracellular signalization cross-regulation. Mol Pharmacol 55:473-480
14. Bracey MH, Hanson MA, Masuda KR, Stevens RC, Cravatt BF (2002) Structural adaptations in a membrane enzyme that terminates endocannabinoid signaling. Science 298:1793-1796
15. Breivogel CS, Griffin G, DiMarzo V, Martin BR (2001) Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol Pharmacol 60:155-163
16. Busch-Petersen J, Hill WA, Fan P, Khanolkar A, Xie XQ, Tius MA, Makriyannis A (1996) Unsaturated side chain beta-11-hydroxyhexahydrocannabinol analogs. J Med Chem 39:3790-3796
17. Chin C, Lucas-Lenard J, Abadji V, Kendall DA(1998)Ligand binding andmodulationof cyclic AMP levels depend on the chemical nature of residue 192 of the human cannabinoid receptor 1. J Neurochem 70:366-373
18. Compton DR, Gold LH, Ward SJ, Balster RL, Martin BR (1992) Aminoalkylindole analogs: Cannabimimetic activity of a class of compounds structurally distinct from delta-9-Tetrahydrocannabinol. J Pharmacol Exp Ther 263:1118-1126
19. Corey EJ, Niwa H, Falck JR (1979) Selective epoxidation of ecosa-cis-5, 8, 11, 14-Tetraenoic (arachidonic) acid and eicosa-cis-8, 11,14-Trienoic acid. J Am Chem Soc 101:1586-1587
20. D'Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC, et al (1992) Conformationally restrained analogues of pravadoline: Nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor. J Med Chem 35:124-135
21. Devane WA, Dysarz FA, 3rd, Johnson MR, Melvin LS, Howlett AC (1988) Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605-613
22. Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946-1949
23. Di Marzo V, Breivogel CS, Tao Q, Bridgen DT, Razdan RK, Zimmer AM, Zimmer A, Martin BR (2000) Levels, metabolism, and pharmacological activity of anandamide in CB(1) cannabinoid receptor knockout mice: Evidence for non-CB(1), non-CB(2) receptormediated actions of anandamide in mouse brain. J Neurochem 75:2434-2444
24. Drake DJ, Jensen RS, Busch-Petersen J, Kawakami JK, Concepcion Fernandez-Garcia M, Fan P, Makriyannis A, Tius MA(1998) Classical/nonclassical hybrid cannabinoids: Southern aliphatic chain-functionalized C-6beta methyl, ethyl, and propyl analogues. JMedChem 41:3596-3608
25. Dutta AK, Ryan W, Thomas BF, Singer M, Compton DR, Martin BR, Razdan RK (1997) Synthesis, pharmacology, and molecularmodeling ofnovel 4-Alkyloxy indole derivatives related to cannabimimetic aminoalkyl indoles (AAIs). Bioorg Med Chem 5:1591-1600
26. Edgemond WS, Campbell WB, Hillard CJ (1995) The binding of novel phenolic derivatives of anandamide to brain cannabinoid receptors. Prostaglandins Leukot Essent Fatty Acids 52:83-86
27. Edgemond WS, Hillard CJ, Falck JR, Kearn CS, Campbell WB (1998) Human platelets and polymorphonuclear leukocytes synthesize oxygenated derivatives of arachidonylethanolamide (anandamide): Their affinities for cannabinoid receptors and pathways of inactivation. Mol Pharmacol 54:180-188
28. Eissenstat MA, Bell MR, D'Ambra TE, Alexander EJ, Daum SJ, Ackerman JH, Gruett MD, Kumar V, Estep KG, Olefirowicz EM, et al (1995) Aminoalkylindoles: Structure-Activity relationships of novel cannabinoid mimetics. J Med Chem 38:3094-3105
29. Felder CC, Joyce KE, Briley EM, Glass M, Mackie KP, Fahey KJ, Cullinan GJ, Hunden DC, Johnson DW, Chaney MO, Koppel GA, Brownstein M(1998) LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J Pharmacol Exp Ther 284:291-297
30. Francisco ME, Seltzman HH, Gilliam AF, Mitchell RA, Rider SL, Pertwee RG, Stevenson LA, Thomas BF (2002) Synthesis and structure-Activity relationships of amide and hydrazide analogues of the cannabinoid CB(1) receptor antagonist N-(piperidinyl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole- 3-carboxami De (SR141716). J Med Chem 45:2708-2719
31. Fride E, Foox A, Rosenberg E, Faigenboim M, Cohen V, Barda L, Blau H, Mechoulam R (2003) Milk intake and survival in newborn cannabinoid CB1 receptor knockout mice: Evidence for a "CB3" receptor. Eur J Pharmacol 461:27-34
32. Gareau Y, Dufresne C, Gallant M, Rochette C, Sawyer N, Slipetz DM, Tremblay N, Weech PK, Metters KM, Labelle M (1996) Structure activity relationships of tetrahydrocannabinol analogues on human cannabinoid receptors. Bioorg Med Chem Lett 6:189-194
33. Gerard CM, Mollereau C, Vassart G, Parmentier M (1991) Molecular cloning of a human cannabinoid receptor which is also expressed in testis. Biochem J 279:129-134
34. Ghanouni P, Gryczynski Z, Steenhuis JJ, Lee TW, Farrens DL, Lakowicz JR, Kobilka BK (2001a) Functionally different agonists induce distinct conformations in the G protein coupling domain of the beta 2 adrenergic receptor. J Biol Chem 276:24433-24436
35. Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK (2001b) Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Natl Acad Sci U S A 98:5997-6002
36. Glass M, Northup JK (1999) Agonist selective regulation of G proteins by cannabinoid CB(1) and CB(2) receptors. Mol Pharmacol 56:1362-1369
37. Goutopoulos A, Fan P, Khanolkar AD, Xie XQ, Lin S, Makriyannis A (2001) Stereochemical selectivity of methanandamides for the CB1 and CB2 cannabinoid receptors and their metabolic stability. Bioorg Med Chem 9:1673-1684
38. Griffin G, Wray EJ, Rorrer WK, Crocker PJ, Ryan WJ, Saha B, Razdan RK, Martin BR, Abood ME (1999) An investigation into the structural determinants of cannabinoid receptor ligand efficacy. Br J Pharmacol 126:1575-1584
39. Griffin G, Tao Q, Abood ME (2000) Cloning and pharmacological characterization of the rat CB(2) cannabinoid receptor. J Pharmacol Exp Ther 292:886-894
40. Guarnieri F, Weinstein H (1996) Conformational memories and the exploration of biologically relevant peptide conformations: An illustration for the gonadotropin-releasing hormone. J Am Chem Soc 118:5580-5589
41. Hanus L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, Pertwee RG, Ross RA, Mechoulam R, Fride E (1999) HU-308: A specific agonist for CB(2), a peripheral cannabinoid receptor. Proc Natl Acad Sci U S A 96:14228-14233
42. Hanus L, Abu-Lafi S, Fride E, Breuer A, Vogel Z, Shalev DE, Kustanovich I, Mechoulam R (2001) 2-Arachidonyl glyceryl ether, an endogenous agonist of the cannabinoid CB1 receptor. Proc Natl Acad Sci U S A 98:3662-3665
43. Hillard CJ, Manna S, Greenberg MJ, DiCamelli R, Ross RA, Stevenson LA, Murphy V, Pertwee RG, Campbell WB (1999) Synthesis and characterization of potent and selective agonists of the neuronal cannabinoid receptor (CB1). J Pharmacol Exp Ther 289:1427-1433
44. Howlett AC, Johnson MR, Melvin LS, Milne GM(1988) Nonclassical cannabinoid analgetics inhibit adenylate cyclase: Development of a cannabinoid receptormodel.Mol Pharmacol 33:297-302
45. Huffman JW, Dai D, Martin BR, Compton DR (1994) Design, synthesis and pharmacology of cannabimimetic indoles. Bioorg Med Chem Lett 4:563-566
46. Huffman JW, Yu S, Showalter V, Abood ME, Wiley JL, Compton DR, Martin BR, Bramblett RD, Reggio PH(1996) Synthesis and pharmacology of a very potent cannabinoid lacking a phenolic hydroxyl with high affinity for the CB2 receptor. J Med Chem 39:3875-3877
47. Huffman JW, Yu S, Liddle J, Wiley JL, Abood M, Martin BR, Aung MM (1998) 1998 Symposium on the Cannabinoids; International Cannabinoid Research Society; Burlington, VT. 10 [ISBN: 09658053-2-096580538]
48. Huffman JW, Liddle J, Yu S, Aung MM, Abood ME, Wiley JL, Martin BR (1999) 3-(1-,1-Dimethylbutyl)-1-deoxy-delta-8-THC and related compounds: Synthesis of selective ligands for the CB2 receptor. Bioorg Med Chem 7:2905-2914
49. Huffman JW, Bushell SM, Miller JR, Wiley JL, Martin BR (2002) 1-Methoxy-, 1-deoxy-11-hydroxy-And 11-hydroxy-1-methoxy-delta-8-Tetrahydrocannabinols: New selective ligands for the CB(2) receptor. Bioorg Med Chem 10:4119-4129
50. Huffman JW, Mabon R, Wu MJ, Lu J, Hart R, Hurst DP, Reggio PH, Wiley JL, Martin BR (2003) 3-Indolyl-1-naphthylmethanes: New cannabimimetic indoles provide evidence for aromatic stacking interactions with the CB(1) cannabinoid receptor. Bioorg Med Chem 11:539-549
51. Hulme EC, Lu ZL, Ward SD, Allman K, Curtis CA (1999) The conformational switch in 7-Transmembrane receptors: Themuscarinic receptor paradigm. Eur J Pharmacol 375:247-260
52. Hurst DP, Lynch DL, Barnett-Norris J, Hyatt SM, Seltzman HH, Zhong M, Song ZH, Nie J, Lewis D, Reggio PH (2002) N-(piperidin-1-yl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4-methyl-1H-p yrazole-3-carboxamide (SR141716A) interaction with LYS 3.28(192) is crucial for its inverse agonism at the cannabinoid CB1 receptor. Mol Pharmacol 62:1274-1287
53. Iwamura H, Suzuki H, Ueda Y, Kaya T, Inaba T (2001) In vitro and in vivo pharmacological characterization of JTE-907, a novel selective ligand for cannabinoid CB2 receptor. J Pharmacol Exp Ther 296:420-425
54. Jarai Z, Wagner JA, Varga K, Lake KD, Compton DR, Martin BR, Zimmer AM, Bonner TI, Buckley NE, Mezey E, Razdan RK, Zimmer A, Kunos G (1999) Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct fromCB1 or CB2 receptors. Proc Natl Acad Sci U S A 96:14136-14141
55. Jensen AD, Guarnieri F, Rasmussen SG, Asmar F, Ballesteros JA, Gether U (2001) Agonistinduced conformational changes at the cytoplasmic side of transmembrane segment 6 in the beta 2 adrenergic receptor mapped by site-selective fluorescent labeling. J Biol Chem 276:9279-9290
56. Kanyonyo M, Govaerts SJ, Hermans E, Poupaert JH, Lambert DM (1999) 3-Alkyl-(5,5-diphenyl)imidazolidineiones as new cannabinoid receptor ligands. Bioorg Med Chem Lett 9:2233-2236
57. Kearn CS, Greenberg MJ, DiCamelli R, Kurzawa K, Hillard CJ (1999) Relationships between ligand affinities for the cerebellar cannabinoid receptor CB1 and the induction of GDP/GTP exchange. J Neurochem 72:2379-2387
58. Keimowitz AR, Martin BR, Razdan RK, Crocker PJ, Mascarella SW, Thomas BF (2000) QSAR analysis of delta-8-THC analogues: Relationship of side-chain conformation to cannabinoid receptor affinity and pharmacological potency. J Med Chem 43:59-70
59. Khanolkar AD, Abadji V, Lin S, Hill WA, Taha G, Abouzid K, Meng Z, Fan P, Makriyannis A (1996) Head group analogs of arachidonylethanolamide, the endogenous cannabinoid ligand. J Med Chem 39:4515-4519
60. Khanolkar AD, LuD, Fan P, Tian X, Makriyannis A (1999)Novel conformationally restricted tetracyclic analogs of delta-8-Tetrahydrocannabinol. BioorgMedChemLett 9:2119-2124
61. Krishnamurthy M, Ferreira AM, Moore BM, 2nd (2003) Synthesis and testing of novel phenyl substituted side-chain analogues of classical cannabinoids. Bioorg Med Chem Lett 13:3487-3490
62. Kumar V, Alexander MD, Bell MR, Eissenstat MA, Casiano FM, Chippari SM, Haycock DA, Luttinger DA, Kuster JE, Miller MS, Stevenson JI, Ward SJ (1995) Morpholinoalkylindenes as antinociceptive agents: Novel cannabinoid receptor agonists. BioorgMedChem Lett 5:381-386
63. Lagu SG, Varona A, Chambers JD, Reggio PH (1995) Construction of a steric map of the binding pocket for cannabinoids at the cannabinoid receptor. Drug Des Discov 12:179-192
64. Lan R, Liu Q, Fan P, Lin S, Fernando SR, McCallion D, Pertwee R, Makriyannis A (1999) Structure-Activity relationships of pyrazole derivatives as cannabinoid receptor antagonists. J Med Chem 42:769-776
65. Lang W, Qin C, Lin S, Khanolkar AD, Goutopoulos A, Fan P, Abouzid K, Meng Z, Biegel D, Makriyannis A(1999) Substrate specificity and stereoselectivity of rat brain microsomal anandamide amidohydrolase. J Med Chem 42:896-902
66. Lange JH, Coolen HK, van Stuivenberg HH, Dijksman JA, Herremans AH, Ronken E, Keizer HG, Tipker K, McCreary AC, Veerman W, Wals HC, Stork B, Verveer PC, den Hartog AP, De Jong NM, Adolfs TJ, Hoogendoorn J, Kruse CG (2004) Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB(1) cannabinoid receptor antagonists. J Med Chem 47:627-643
67. Lin S, Khanolkar AD, Fan P, Goutopoulos A, Qin C, Papahadjis D, Makriyannis A (1998) Novel analogues of arachidonylethanolamide (anandamide): Affinities for the CB1 and CB2 cannabinoid receptors and metabolic stability. J Med Chem 41:5353-5361
68. Makriyannis A, Rapaka RS (1990) The molecular basis of cannabinoid activity. Life Sci 47:2173-2184
69. Martin BR, Jefferson R, Winckler R, Wiley JL, Huffman JW, Crocker PJ, Saha B, Razdan RK (1999)Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists. J Pharmacol Exp Ther 290:1065-1079
70. Mato S, Pazos A, Valdizan EM(2002) Cannabinoid receptor antagonism and inverse agonism in response to SR141716A oncAMPproduction in humanand rat brain. Eur J Pharmacol 443:43-46
71. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561-564
72. McAllister SD, Rizvi G, Anavi-Goffer S, Hurst DP, Barnett-Norris J, Lynch DL, Reggio PH, Abood ME (2003) An aromatic microdomain at the cannabinoid CB(1) receptor constitutes an agonist/inverse agonist binding region. J Med Chem 46:5139-5152
73. Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, et al (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83-90
74. Melvin LS, Johnson MR (1987) Structure-Activity relationships of tricyclic and nonclassical bicyclic cannabinoids. NIDA Res Monogr 79:31-47
75. Melvin LS, Milne GM, Johnson MR, Subramaniam B, Wilken GH, Howlett AC (1993) Structure-Activity relationships for cannabinoid receptor-binding and analgesic activity: Studies of bicyclic cannabinoid analogs. Mol Pharmacol 44:1008-1015
76. Melvin LS, Milne GM, Johnson MR, Wilken GH, Howlett AC (1995) Structure-Activity relationships defining the ACD-Tricyclic cannabinoids: Cannabinoid receptor binding and analgesic activity. Drug Des Discov 13:155-166
77. Meschler JP, Kraichely DM, Wilken GH, Howlett AC (2000) Inverse agonist properties of N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4- methyl-1H-pyrazole-3-carboxamideHCl (SR141716A) and 1-(2-chlorophenyl)-4-cyano- 5-(4-methoxyphenyl)-1H-pyrazole-3-carboxylic acid phenylamide (CP-272871) for the CB(1) cannabinoid receptor. Biochem Pharmacol 60:1315-1323
78. Mignani S, Hittinger O, Archard D, Bouchard H, Bouquerel J, Capet M, Grisoni S, Malleron JL (2000) Preparation of 1-bis(aryl)methyl-3-(alkylsulfonyl) arylmethyleneazetidines as cannabinoid CB1 receptor antagonists. Chemical Abstracts. Aventis Pharma SA, France, p 236982s
79. Munro S, Thomas KL, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61-65
80. Mussinu JM, Ruiu S, Mule AC, Pau A, Carai MA, Loriga G, Murineddu G, Pinna GA (2003) Tricyclic pyrazoles. Part 1: Synthesis and biological evaluation of novel 1,4-dihydroindeno[1,2-c]pyrazol-based ligands for CB(1)and CB(2)cannabinoid receptors. Bioorg Med Chem 11:251-263
81. Nadipuram AK, Krishnamurthy M, Ferreira AM, Li W, Moore BM (2003) Synthesis and testing of novel classical cannabinoids: Exploring the side chain ligand binding pocket of the CB1 and CB2 receptors. Bioorg Med Chem 11:3121-3132
82. Nakanishi K, Zhang H, Lerro KA, Takekuma S, Yamamoto T, Lien TH, Sastry L, Back D-J, Moquin-Pattey C, Boehm MF, Derguini F, Gawinowicz MA(1995) Photoaffinity labeling of rhodopsin and bacteriorhodopsin. Biophys Chem 56:13-22
83. Ng EW, Aung MM, Abood ME, Martin BR, Razdan RK (1999) Unique analogues of anandamide: Arachidonyl ethers and carbamates and norarachidonyl carbamates and ureas. J Med Chem 42:1975-1981
84. Ooms F, Wouters J, Oscari O, Happaerts T, Bouchard G, Carrupt PA, Testa B, Lambert DM (2002) Exploration of the pharmacophore of 3-Alkyl-5- Arylimidazolidinediones as new CB(1) cannabinoid receptor ligands and potential antagonists: Synthesis, lipophilicity, affinity, and molecular modeling. J Med Chem 45:1748-1756
85. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M(2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science 289:739-745
86. Pan X, Ikeda SR, Lewis DL (1998) SR 141716A acts as an inverse agonist to increase neuronal voltage-dependentCa2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Mol Pharmacol 54:1064-1072
87. Papahatjis DP, Kourouli T, Abadji V, Goutopoulos A, Makriyannis A (1998) Pharmacophoric requirements for cannabinoid side chains: Multiple bond and C1-substituted delta-8-Tetrahydrocannabinols. J Med Chem 41:1195-1200
88. Papahatjis DP, Nikas SP, Andreou T, Makriyannis A (2002) Novel 1-,1-chain substituted delta-8-Tetrahydrocannabinols. Bioorg Med Chem Lett 12:3583-3586
89. Pinto JC, Potie F, Rice KC, Boring D, Johnson MR, Evans DM, Wilken GH, Cantrell CH, Howlett AC (1994) Cannabinoid receptor binding and agonist activity of amides and esters of arachidonic acid. Mol Pharmacol 46:516-522
90. Rabinovich AL, Ripatti PO (1991) On the conformational, physical properties and function of polyunsaturated AcylChains. Biochim Biophys Acta 1085:53-56
91. Razdan RK (1986) Structure-Activity relationships in cannabinoids. Pharmacol Rev 38:75-149
92. Reggio PH, Traore H(2000) Conformational requirements for endocannabinoid interaction with the cannabinoid receptors, the anandamide transporter and fatty acid amidohydrolase. Chem Phys Lipids 108:15-35
93. Reggio PH, Panu AM, Miles S (1993) Characterization of a region of steric interference at the cannabinoid receptor using the active analog approach. J Med Chem 36:1761-1771
94. Reggio PH, Wang T, Brown AE, Fleming DN, Seltzman HH, Griffin G, Pertwee RG, Compton DR, Abood ME, Martin BR (1997) Importance of the C-1 substituent in classical cannabinoids to CB2 receptor selectivity: Synthesis and characterization of a series of O,2-propano-delta-8-Tetrahydrocannabinol analogs. J Med Chem 40:3312-3318
95. Reggio PH, Basu-Dutt S, Barnett-Norris J, Castro MT, Hurst DP, Seltzman HH, Roche MJ, Gilliam AF, Thomas BF, Stevenson LA, Pertwee RG, Abood ME (1998) The bioactive conformation of aminoalkylindoles at the cannabinoid CB1 and CB2 receptors: Insights gained from (E)-And (Z)-naphthylidene indenes. J Med Chem 41:5177-5187
96. Rich MR(1993) Conformational analysis of arachidonic and related fatty acids using molecular dynamics simulations. Biochim Biophys Acta 1178:87-96
97. Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Neliat G, Caput D, et al (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240-244
98. Rinaldi-Carmona M, Barth F, Millan J, Derocq JM, Casellas P, Congy C, Oustric D, Sarran M, Bouaboula M, Calandra B, Portier M, Shire D, Breliere JC, Le Fur GL (1998) SR 144528, the first potent and selective antagonist of the CB2 cannabinoid receptor. J Pharmacol Exp Ther 284:644-650
99. Ross RA, Brockie HC, Fernando SR, Saha B, Razdan RK, Pertwee RG (1998) Comparison of cannabinoid binding sites in guinea-pig forebrain and small intestine. Br J Pharmacol 125:1345-1351
100. Ross RA, Brockie HC, Stevenson LA, Murphy VL, Templeton F, Makriyannis A, Pertwee RG (1999a) Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630. Br J Pharmacol 126:665-672
101. Ross RA, Gibson TM, Stevenson LA, Saha B, Crocker P, Razdan RK, Pertwee RG (1999b) Structural determinants of the partial agonist-inverse agonist properties of 6-Azidohex-2-yne-delta-8-Tetrahydrocannabinol at cannabinoid receptors. Br J Pharmacol 128:735-743
102. Ruiu S, Pinna GA, Marchese G, Mussinu JM, Saba P, Tambaro S, Casti P, Vargiu R, Pani L (2003) Synthesis and characterization of NESS 0327: A novel putative antagonist of the CB1 cannabinoid receptor. J Pharmacol Exp Ther 306:363-370
103. Ryan W, Singer M, Razdan RK, Compton DR, Martin BR (1995) A novel class of potent tetrahydrocannabinols (THCS): 2-yne-delta-8-And delta-9-THCs. Life Sci 56:2013-2020
104. Ryan WJ, Banner WK, Wiley JL, Martin BR, Razdan RK (1997) Potent anandamide analogs: The effect of changing the length and branching of the end pentyl chain. J Med Chem 40:3617-3625
105. Salo OM, Lahtela-Kakkonen M, Gynther J, Jarvinen T, Poso A (2004) Development of a 3D model for the human cannabinoid CB1 receptor. J Med Chem 47:3048-3057
106. Seltzman HH, Fleming DN, Thomas BF, Gilliam AF, McCallion DS, Pertwee RG, Compton DR, Martin BR (1997) Synthesis and pharmacological comparison of dimethylheptyl and pentyl analogs of anandamide. J Med Chem 40:3626-3634
107. Sheskin T, Hanus L, Slager J, Vogel Z, Mechoulam R (1997) Structural requirements for binding of anandamide-Type compounds to the brain cannabinoid receptor. J Med Chem 40:659-667
108. Shim JY, Collantes ER, Welsh WJ, Subramaniam B, Howlett AC, Eissenstat MA, Ward SJ (1998) Three-dimensional quantitative structure-Activity relationship study of the cannabimimetic (aminoalkyl)indoles using comparative molecular field analysis. JMed Chem 41:4521-4532
109. Shim JY, Welsh WJ, Cartier E, Edwards JL, Howlett AC(2002)Molecular interaction of the antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4- dichlorophenyl)-4-methyl-1Hpyrazole-3-carboxamide with the CB1 cannabinoid receptor. JMed Chem 45:1447-1459
110. Shim JY, Welsh WJ, Howlett AC (2003) Homology model of the CB1 cannabinoid receptor: Sites critical for nonclassical cannabinoid agonist interaction. Biopolymers 71:169-189
111. Shire D, Carillon C, Kaghad M, Calandra B, Rinaldi-Carmona M, Le Fur G, Caput D, Ferrara P (1995) An amino-Terminal variant of the central cannabinoid receptor resulting from alternative splicing. J Biol Chem 270:3726-3731
112. Shire D, Calandra B, Rinaldi-Carmona M, Oustric D, Pessegue B, Bonnin-Cabanne O, Le Fur G, Caput D, Ferrara P (1996)Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. Biochim Biophys Acta 1307:132-136
113. Shire D, Calandra B, Bouaboula M, Barth F, Rinaldi-Carmona M, Casellas P, Ferrara P (1999) Cannabinoid receptor interactions with the antagonists SR 141716A and SR 144528. Life Sci 65:627-635
114. Sim-Selley LJ, Brunk LK, Selley De (2001) Inhibitory effects of SR141716A on G-protein activation in rat brain. Eur J Pharmacol 414:135-143
115. Singer M, Ryan WJ, Saha B, Martin BR, Razdan RK (1998) Potent cyano and carboxamido side-chain analogues of 1-, 1-dimethyl-delta-8-Tetrahydrocannabinol. J Med Chem 41:4400-4407
116. Song ZH, Bonner TI (1996) A lysine residue of the cannabinoid receptor is critical for receptor recognition by several agonists but not WIN55212-2. Mol Pharmacol 49:891-896
117. Song ZH, Slowey CA, Hurst DP, Reggio PH (1999) The difference between the CB(1) and CB(2) cannabinoid receptors at position 5.46 is crucial for the selectivity of WIN55212-2 for CB(2). Mol Pharmacol 56:834-840
118. Stegeman R, Pawlitz J, Stevens A, Gierse J, Stallings W, Kurumbail R (1998) Mechanism of cyclooxygenase reactions: Structure of arachidonic acid bound to cyclooxygenase-2. American Crystallographic Association. Abstract
119. Stella N, Schweitzer P, Piomelli D (1997) A second endogenous cannabinoid that modulates long-Term potentiation. Nature 388:773-778
120. Stoit AR, Lange JHM, den Hartog AP, Ronken E, Tipker K, van Stuivenberg HH, Dijksman JAR, Wals HC, Kruse CG (2002) Design, synthesis and biological activity of rigid cannabinoid CB1 receptor antagonists. Chem Pharm Bull (Tokyo) 50:1109-1113
121. Thomas BF, Compton DR, Martin BR, Semus SF (1991)Modeling the cannabinoid receptor: A three-dimensional quantitative structure-Activity analysis.Mol Pharmacol 40:656-665
122. Thomas BF, Adams IB, Mascarella SW, Martin BR, Razdan RK (1996) Structure-Activity analysis of anandamide analogs: Relationship to a cannabinoid pharmacophore. J Med Chem 39:471-479
123. Thomas BF, Gilliam AF, Burch DF, Roche MJ, Seltzman HH (1998) Comparative receptor binding analyses of cannabinoid agonists and antagonists. J Pharmacol Exp Ther 285:285-292
124. Tius MA, Makriyannis A, Zoua XL, Abadji V (1994) Conformationally restricted hybrids of CP-55,940 and HHC: Stereoselective synthesis and activity. Tetrahedron 50:2671-2680
125. Tong W, Collantes ER, Welsh WJ, Berglund BA, Howlett AC (1998) Derivation of a pharmacophore model for anandamide using constrained conformational searching and comparative molecular field analysis. J Med Chem 41:4207-4215
126. van der Stelt M, van Kuik JA, Bari M, van Zadelhoff G, Leeflang BR, Veldink GA, Finazzi-Agro A, Vliegenthart JF, Maccarrone M (2002) Oxygenated metabolites of anandamide and 2-Arachidonoylglycerol: Conformational analysis and interaction with cannabinoid receptors, membrane transporter, and fatty acid amide hydrolase. JMed Chem 45:3709-3720
127. Wagner JA, Varga K, Jarai Z, Kunos G(1999)Mesenteric vasodilationmediatedbyendothelial anandamide receptors. Hypertension 33:429-434
128. Ward SJ, Baizman E, Bell M, Childers S, D'Ambra T, Eissenstat M, Estep K, Haycock D, Howlett A, Luttinger D, et al (1991) Aminoalkylindoles (AAIs): A new route to the cannabinoid receptor? NIDA Res Monogr 105:425-426
129. Wiley JL, Compton DR, Dai D, Lainton JA, Phillips M, Huffman JW, Martin BR (1998) Structure-Activity relationships of indole-And pyrrole-derived cannabinoids. J Pharmacol Exp Ther 285:995-1004
130. Wiley JL, Jefferson RG, Grier MC, Mahadevan A, Razdan RK, Martin BR (2001) Novel pyrazole cannabinoids: Insights into CB(1) receptor recognition and activation. J Pharmacol Exp Ther 296:1013-1022
131. Wiley JL, Beletskaya ID, Ng EW, Dai Z, Crocker PJ, Mahadevan A, Razdan RK, Martin BR (2002) Resorcinol derivatives: A novel template for the development of cannabinoid CB(1)/CB(2) and CB(2)-selective agonists. J Pharmacol Exp Ther 301:679-689
132. Xie XQ, Yang DP, Melvin LS, Makriyannis A(1994) Conformational analysis of the prototype nonclassical cannabinoid CP-47,497, using 2DNMRand computer molecularmodeling. J Med Chem 37:1418-1426
133. Xie XQ, Eissenstat M, Makriyannis A (1995) Common cannabimimetic pharmacophoric requirements between aminoalkyl indoles and classical cannabinoids. Life Sci 56:1963-1970
134. Xie XQ, Melvin LS, Makriyannis A (1996) The conformational properties of the highly selective cannabinoid receptor ligand CP-55,940. J Biol Chem 271:10640-10647
135. Xie XQ, Pavlopoulos S, DiMeglio CM, Makriyannis A (1998) Conformational studies on a diastereoisomeric pair of tricyclic nonclassical cannabinoids by NMR spectroscopy and computer molecular modeling. J Med Chem 41:167-174
136. Xie XQ, Han XW, Chen JZ, Eissenstat M, Makriyannis A (1999) High-resolution NMR and computer modeling studies of the cannabimimetic aminoalkylindole prototype WIN-55212-2. J Med Chem 42:4021-4027
137. Xie XQ, Chen JZ, Billings EM(2003) 3D structural model of the G-protein-coupled cannabinoid CB2 receptor. Proteins 53:307-319