Toward the design of cannabinoid CB1 receptor inverse agonists and neutral antagonists

Drug Development Research

Volumn 70, Issue 8, 2009, Pages 585-600

  Reggio, Patricia H ^a  

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

Author keywords

Cannabinoid; G protein coupled receptor; Inverse agonism; Neutral antagonism

Indexed keywords

2 ARACHIDONOYLGLYCEROL; 2,3 DIHYDRO 5 METHYL 3 (MORPHOLINOMETHYL) 6 (1 NAPHTHOYL)PYRROLO[1,2,3 DE][1,4]BENZOXAZINE; 4 (1,1 DIMETHYLHEPTYL) 1',2',3',4',5',6' HEXAHYDRO 2,3' DIHYDROXY 6' (3 HYDROXYPROPYL)BIPHENYL; 4 [6 METHOXY 2 (4 METHOXYPHENYL) 3 BENZOFURANYLCARBONYL]BENZONITRILE; AM 4113; ANANDAMIDE; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CARAZOLOL; CP 272871; DRINABANT; G PROTEIN COUPLED RECEPTOR; HEMOPRESSIN; IBIPINABANT; JHU 75528; LH 21; O 1184; OTENABANT; RHODOPSIN; RIMONABANT; TARANABANT; UNCLASSIFIED DRUG;

ALLOSTERISM; ALZHEIMER DISEASE; BONE DISEASE; CLINICAL TRIAL; COGNITIVE DEFECT; COMPUTER MODEL; DEPRESSION; DRUG ANTAGONISM; DRUG BINDING SITE; DRUG DESIGN; DRUG ISOLATION; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG RECEPTOR BINDING; DRUG STRUCTURE; HUMAN; LIGAND BINDING; LIVER FIBROSIS; MENTAL DISEASE; METABOLIC SYNDROME X; NONHUMAN; OBESITY; PROTEIN DOMAIN; PROTEIN STRUCTURE; REVIEW; SUICIDAL IDEATION;

EID: 74549134507     PISSN: 02724391     EISSN: 10982299     Source Type: Journal    
DOI: 10.1002/ddr.20337     Document Type: Review

References (106)

1. 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.
2. Antel J, Gregory PC, Nordheim U. 2006. CB1 cannabinoid receptor antagonists for treatment of obesity and prevention of comorbid metabolic disorders. J Med Chem 49:4008-4016.
3. Ballesteros J, Jensen A, Liapakis G, Rasmussen S, Shi L, Gether U, Javitch J. 2001. Activation of the b2 adrenergic receptor involves disruption of an ionic link between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 276:29171-29177.
4. Ballesteros JA, Weinstein H. 1995. Integrated methods for the construction of three dimensional models and computational probing of structure function relations in G protein-coupled receptors. In: Sealfon SC, editor. Methods in neuroscience. San Diego, CA: Academic Press. p 366-428.
5. Barnett-Norris J, Hurst DP, Buehner K, Ballesteros JA, Guarnieri F, Reggio PH. 2002. Agonist alkyl tail interaction with cannabinoid CB1 receptor V6.43/I6.46 groove induces a Helix 6 active conformation. Int J Quantum Chem 88:76-86.
6. Barnett-Norris J, Hurst DP, Reggio PH. 2003. The influence of cannabinoid receptor second extracellular loop conformation on the binding of CP55940. Cornwall, Ontario: International Cannabinoid Research Society. p 79.
7. Borhan B, Souto ML, Imai H, Shichida Y, Nakanishi K. 2000. Movement of retinal along the visual transduction path. Science 288:2209-2212.
8. Bouaboula M, Rinaldi M, Carayon P, Carillon C, Delpech B, Shire D, Le Fur G, Casellas P. 1993. Cannabinoid-receptor expression in human leukocytes. Eur J Biochem 214:173-180.
9. 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.
10. 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.
11. Cervino C, Pasquali R, Pagotto U. 2007. Cannabinoid receptor antagonists and the metabolic syndrome: novel promising therapeutical approaches. Mini Rev Med Chem 7:21-30.
12. 1 receptor. Eur J Pharmacol 584:338-342.
13. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC. 2007. High-resolution crystal structure of an engineered human {beta}2-adrenergic G protein coupled receptor. Science 318:1258-1265.
14. Christopoulos A. 2002. Allosteric binding sites on cell-surface receptors: novel targets for drug discovery. Nat Rev Drug Discov 1:198-210.
15. 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.
16. D'Ambra TE, Estep KG, Bell MR, Eissenstat MA, Josef KA, Ward SJ, Haycock DA, Baizman ER, Casiano FM, Beglin NC, Chippari SM, Grego JD, Kullnig II RK, Daley GT. 1992. Conformationally restrained analogues of pravadoline: nanomolar potent, enantioselective, (aminoalkyl)indole agonists of the cannabinoid receptor. J Med Chem 35:124-135.
17. Devane WA, Dysarz III FA, Johnson MR, Melvin LS, Howlett AC. 1988. Determination and characterization of a cannabinoid receptor in rat brain. Mol Pharmacol 34:605-613.
18. 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.
19. Farrens D, Altenbach C, Ynag K, Hubbell W, Khorana H. 1996. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274:768-770.
20. Fay JF, Dunham TD, Farrens DL. 2005. Cysteine residues in the human cannabinoid receptor: only C257 and C264 are required for a functional receptor, and steric bulk at C386 impairs antagonist SR141716A binding. Biochemistry 44:8757-8769.
21. Felder CC, Joyce KE, Briley EM, Glass M, Mackie KP, Fahey KJ, Cullinan GJ, Hunden DC, Johnson DW, Chaney MO, et al. 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.
22. Fride E, Braun H, Matan H, Steinberg S, Reggio PH, Seltzman HH. 2007. Inhibition of milk ingestion and growth after administration of a neutral cannabinoid CB1 receptor antagonist on the first postnatal day in the mouse. Pediatr Res 62:533-536.
23. Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P. 1995. Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54-61.
24. 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(Pt 1):129-134.
25. Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK. 2001. Agonistinduced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Natl Acad Sci USA 98:5997-6002.
26. Glass M, Dragunow M, Faull RL. 1997. Cannabinoid receptors in the human brain: a detailed anatomical and quantitative autoradiographic study in the fetal, neonatal and adult human brain. Neuroscience 77:299-318.
27. Greasley PJ, Clapham JC. 2006. Inverse agonism or neutral antagonism at G-protein coupled receptors: a medicinal chemistry challenge worth pursuing? Eur J Pharmacol 553:1-9.
28. 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.
29. 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 USA 98:3662-3665.
30. Hassan SA, Guarnieri F, Mehler EL. 2000a. A general treatment of solvent effects based on screened coulomb potentials. J Phys Chem B 104:6478-6489.
31. Hassan SA, Guarnieri F, Mehler EL. 2000b. Characterization of hydrogen bonding in a continuum solvent model. J Phys Chem B 104:6490-6498.
32. Hassan SA, Mehler EL, Weinstein H. 2002. Structure calculation of protein segments connecting domains with defined secondary structure: a simulated annealing Monte Carlo combined with biased scaled collective variables technique. In: Schlick T, Gan HH, editors. Computational methods for macromolecules: Challenges and applications. New York: Springer Verlag. p 197-231.
33. Heimann AS, Gomes I, Dale CS, Pagano RL, Gupta A, de Souza LL, Luchessi AD, Castro LM, Giorgi R, Rioli V, Ferro ES, Devi LA. 2007. Hemopressin is an inverse agonist of CB1 cannabinoid receptors. Proc Natl Acad Sci USA 104:20588-20593.
34. 1 receptors with hypophagic effects in rats. Br J Pharmacol 152:805-814.
35. 11C- JHU75528: a radiotracer for PET imaging of CB1 cannabinoid receptors. J Nucl Med 47:1689-1696.
36. 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.
37. Hurst D, Umejiego U, Lynch D, Seltzman H, Hyatt S, Roche M, McAllister S, Fleischer D, Kapur A, Abood M, Shi S, Jones J, Lewis D, Reggio PH. 2006. Biarylpyrazole inverse agonists at the cannabinoid CB1 receptor: importance of the C-3 carboxamide oxygen/lysine3.28(192) interaction. J Med Chem 49:5969-5987.
38. Idris AI, van't Hof RJ, Greig IR, Ridge SA, Baker D, Ross RA, Ralston SH. 2005. Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med 11:774-779.
39. Iiri T, Farfel Z, Bourne HR. 1998. G-protein diseases furnish a model for the turn-on switch. Nature 394:35-38.
40. Ishac EJ, Jiang L, Lake KD, Varga K, Abood ME, Kunos G. 1996. Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves. Br J Pharmacol 118:2023-2028.
41. Jagerovic N, Fernandez-Fernandez C, Goya P. 2008. CB1 cannabinoid antagonists: structure-activity relationships and potential therapeutic applications. Curr Top Med Chem 8:205-230.
42. Javitch JA, Fu D, Liapakis G, Chen J. 1997. Constitutive activation of the beta2 adrenergic receptor alters the orientation of its sixth membrane-spanning segment. J Biol Chem 272:18546-18549.
43. Jensen AD, Guarnieri F, Rasmussen SG, Asmar F, Ballesteros JA, Gether U. 2001. Agonist-induced 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.
44. Jonsson KO, Holt S, Fowler CJ. 2006. The endocannabinoid system: current pharmacological research and therapeutic possibilities. Basic Clin Pharmacol Toxicol 98:124-134.
45. Kapur A, Hurst DP, Fleischer D, Whitnell R, Thakur GA, Makriyannis A, Reggio PH, Abood ME. 2007. Mutation studies of Ser7.39 and Ser2.60 in the human CB1 cannabinoid receptor: evidence for a serine-induced bend in CB1 transmembrane Helix 7. Mol Pharmacol 71:1512-1524.
46. 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.
47. Kobilka BK, Deupi X. 2007. Conformational complexity of G-protein-coupled receptors. Trends Pharmacol Sci 28:397-406.
48. Lange JH, Coolen HK, van Stuivenberg HH, Dijksman JA, Herremans AH, Ronken E, Keizer HG, Tipker K, McCreary AC, Veerman W, et al. 2004. Synthesis, biological properties, and molecular modeling investigations of novel 3,4-diarylpyrazolines as potent and selective CB1 cannabinoid receptor antagonists. J Med Chem 47:627-643.
49. Langmead CJ, Christopoulos A. 2006. Allosteric agonists of 7TM receptors: expanding the pharmacological toolbox. Trends Pharmacol Sci 27:475-481.
50. Leff P. 1995. The two-state model of receptor activation. Trends Pharmacol Sci 16:89-97.
51. Li J, Edwards PC, Burghammer M, Villa C, Schertler GF. 2004. Structure of bovine rhodopsin in a trigonal crystal form. J Mol Biol 343:1409-1438.
52. Lin LS, Lanza Jr TJ, Jewell JP, Liu P, Shah SK, Qi H, Tong X, Wang J, Xu SS, Fong TM, Shen CP, Lao J, Xiao JC, Shearman LP, Stribling DS, Rosko K, Strack A, Marsh DJ, Feng Y, Kumar S, Samuel K, Yin W, Van der Ploeg LH, Goulet MT, Hagmann WK. 2006. Discovery of N-[(1S,2S)-3-(4-Chlorophenyl)-2-(3-cyanophenyl)- 1-methylpropyl]-2-methyl-2-[5-(trifluoromethyl)pyridin-2-yl]oxypropanamide (MK-0364), a novel, acyclic cannabinoid-1 receptor inverse agonist for the treatment of obesity. J Med Chem 49:7584-7587.
53. Lin S, Sakmar T. 1996a. Specific tryptophan UV-absorbance changes are probes of the transition of rhodopsin to its active state. Biochemistry 35:11149-11159.
54. Lin SW, Sakmar TP. 1996b. Specific tryptophan UV-absorbance changes are probes of the transition of rhodopsin to its active state. Biochemistry 35:11149-11159.
55. Makriyannis A, Mechoulam R, Piomelli D. 2005. Therapeutic opportunities through modulation of the endocannabinoid system. Neuropharmacology 48:1068-1071.
56. Mato S, Pazos A, Valdizan EM. 2002. Cannabinoid receptor antagonism and inverse agonism in response to SR141716A on cAMP production in human and rat brain. Eur J Pharmacol 443:43-46.
57. 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.
58. Mazzoni MR, Hamm HH. 2000. Limited proteolytic digestion studies of G protein-receptor interactions. Methods Enzymol 315:363-376.
59. McAllister SD, Tao Q, Barnett-Norris J, Buehner K, Hurst DP, Guarnieri F, Reggio PH, Nowell Harmon KW, Cabral GA, Abood ME. 2002. A critical role for a tyrosine residue in the cannabinoid receptors for ligand recognition. Biochem Pharmacol 63:2121-2136.
60. 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 CB1 receptor constitutes an agonist/inverse agonist binding region. J Med Chem 46: 5139-5152.
61. McAllister SD, Hurst DP, Barnett-Norris J, Lynch D, Reggio PH, Abood ME. 2004. Structural mimicry in class A G proteincoupled receptor rotamer toggle switches: the importance of the F3.36(201)/W6.48(357) interaction in cannabinoid CB1 receptor activation. J Biol Chem 279:48024-48037.
62. 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.
63. 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.
64. 1 cannabinoid receptor. Biochem Pharmacol 60: 1315-1323.
65. Nakanishi J, Takarada T, Yunoki S, Kikuchi Y, Maeda M. 2006. FRET-based monitoring of conformational change of the beta2 adrenergic receptor in living cells. Biochem Biophys Res Commun 343:1191-1196.
66. Okada T, Fujiyoshi Y, Silow M, Navarro J, Landau EM, Shichida Y. 2002. Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc Natl Acad Sci USA 99:5982-5987.
67. Okada T, Sugihara M, Bondar AN, Elstner M, Entel P, Buss V. 2004. The retinal conformation and its environment in rhodopsin in light of a new 2.2Å crystal structure. J Mol Biol 342: 571-583.
68. 2+ currents by reversal of tonic CB1 cannabinoid receptor activity. Mol Pharmacol 54:1064-1072.
69. 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.
70. Pertwee RG. 1997. Pharmacology of cannabinoid CB1 and CB2 receptors. Pharmacol Ther 74:129-180.
71. Pertwee RG. 2005a. Inverse agonism and neutral antagonism at cannabinoid CB1 receptors. Life Sci 76:1307-1324.
72. Pertwee RG. 2005b. The therapeutic potential of drugs that target cannabinoid receptors or modulate the tissue levels or actions of endocannabinoids. Aaps J 7:E625-E654.
73. Picone RP, Khanolkar AD, Xu W, Ayotte LA, Thakur GA, Hurst DP, Abood ME, Reggio PH, Fournier DJ, Makriyannis A. 2005. (-)-7′-Isothiocyanato-11- hydroxy-1′,1′-dimethylheptylhexahydrocannabinol (AM841), a high-affinity electrophilic ligand, interacts covalently with a cysteine in helix six and activates the CB1 cannabinoid receptor. Mol Pharmacol 68:1623-1635.
74. Price MR, Baillie GL, Thomas A, Stevenson LA, Easson M, Goodwin R, McLean A, McIntosh L, Goodwin G, Walker G, Westwood P, Marrs J, Thomson F, Cowley P, Christopoulos CA, Pertwee RG, Ross RA. 2005. Allosteric modulation of the cannabinoid CB1 receptor. Mol Pharmacol 68:1484-1495.
75. Ramos JA, Gonzalez S, Sagredo O, Gomez-Ruiz M, Fernandez-Ruiz J. 2005. Therapeutic potential of the endocannabinoid system in the brain. Mini Rev Med Chem 5:609-617.
76. Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK. 2007. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450:383-387.
77. Reggio P, Grossfield A, Hurst D, Lynch D, Gawrisch K, Pitman M. 2008. Microsecond time scale molecular dynamics simulations: endocannabinoid entry into the cannabinoid CB2 receptor via the lipid bilayer, Feb 2-6, 2008; Long Beach, CA. Biophysical Society.
78. 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.
79. Rice W, Shannon JM, Burton F, Fiedeldey D. 1997. Expression of a brain-type cannabinoid receptor (CB1) in alveolar Type II cells in the lung: regulation by hydrocortisone. Eur J Pharmacol 327: 227-232.
80. Rinaldi-Carmona M, Barth F, Heaulme M, Shire D, Calandra B, Congy C, Martinez S, Maruani J, Neliat G, Caput D, Ferrara P, Soubrie P, Breliere JC, Le Fur G. 1994. SR141716A, a potent and selective antagonist of the brain cannabinoid receptor. FEBS Lett 350:240-244.
81. Roche R, Hoareau L, Bes-Houtmann S, Gonthier MP, Laborde C, Baron JF, Haffaf Y, Cesari M, Festy F. 2006. Presence of the cannabinoid receptors, CB1 and CB2, in human omental and subcutaneous adipocytes. Histochem Cell Biol 126:177-187.
82. Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK. 2007. GPCR engineering yields high-resolution structural insights into {beta}2 adrenergic receptor function. Science 318:1266-1273.
83. 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.
84. Salamone JD, McLaughlin PJ, Sink K, Makriyannis A, Parker LA. 2007. Cannabinoid CB1 receptor inverse agonists and neutral antagonists: effects on food intake, food-reinforced behavior and food aversions. Physiol Behav 91:383-388.
85. Salom D, Lodowski DT, Stenkamp RE, Trong IL, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K. 2006. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci USA 103:16123-16128.
86. Samama P, Pei G, Costa T, Cotecchia S, Lefkowitz RJ. 1994. Negative antagonists promote an inactive conformation of the beta 2-adrenergic receptor. Mol Pharmacol 45:390-394.
87. Schuel H, Chang MC, Burkman LJ, Picone RP, Makriyannis A, Zimmerman AM, Zimmerman S. 1999. Cannabinoid receptors in sperm marijuana and medicine. Totowa, NJ: Humana Press. p 335-345.
88. Shi L, Liapakis G, Xu R, Guarnieri F, Ballesteros JA, Javitch JA. 2002. Beta 2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch. J Biol Chem 277:40989-40996.
89. 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.
90. Shim JY, Howlett AC. 2006. WIN55212-2 docking to the CB1 cannabinoid receptor and multiple pathways for conformational induction. J Chem Inf Model 46:1286-1300.
91. 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.
92. 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.
93. Sidló Z, Reggio PH, Rice ME. 2008. Inhibition of striatal dopamine release by CB1 receptor activation requires nonsynaptic communication via GABA, H2O2, and KATP channels. Neurochem Int 52:80-88.
94. 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.
95. Singh R, Hurst DP, Barnett-Norris J, Lynch DL, Reggio PH, Guarnieri F. 2002. Activation of the cannabinoid CB1 receptor may involve a W6.48/F3.36 rotamer toggle switch. J Pept Res 60:357-370.
96. 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.
97. Stella N, Schweitzer P, Piomelli D. 1997. A second endogenous cannabinoid that modulates long-term potentiation. Nature 388:773-778.
98. 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 50: 1109-1113.
99. Straiker AJ, Maguire G, Mackie K, Lindsey J. 1999. Localization of cannabinoid CB1 receptors in the human anterior eye and retina. Invest Ophthalmol Vis Sci 40:2442-2448.
100. Teixeira-Clerc F, Julien B, Grenard P, Tran Van Nhieu J, Deveaux V, Li L, Serriere-Lanneau V, Ledent C, Mallat A, Lotersztajn S. 2006. CB1 cannabinoid receptor antagonism: a new strategy for the treatment of liver fibrosis. Nat Med 12:671-676.
101. Visiers I, Ebersole BJ, Dracheva S, Ballesteros J, Sealfon SC, Weinstein H. 2002. Structural motifs as functional microdomains in G-protein-coupled receptors: Energetic considerations in the mechanism of activation of the serotonin 5-HT2a receptor by disruption of the ionic lock of the arginine cage. Int J Quantum Chem 88:65-75.
102. Ward SJ, Baizman E, Bell M, Childers S, D'Ambra T, Eissenstat M, Estep K, Haycock D, Howlett A, Luttinger D. 1991. Aminoalkylindoles (AAIs): a new route to the cannabinoid receptor? NIDA Res Monogr 105:425-426.
103. Wess J. 1997. G-protein-coupled receptors: molecular mechanisms involved in receptor activation and selectivity of G-protein recognition. FASEB J 11:346-354.
104. Westlake TM, Howlett AC, Bonner TI, Matsuda LA, Herkenham M. 1994. Cannabinoid receptor binding and messenger RNA expression in human brain: an in vitro receptor autoradiography and in situ hybridization histochemistry study of normal aged and Alzheimer's brains. Neuroscience 63:637-652.
105. Whitnell RM, Hurst DP, Reggio PH, Guarnieri F. 2007. Conformational memories with variable bond angles. J Comput Chem 29:741-752.
106. Wright K, Rooney N, Feeney M, Tate J, Robertson D, Welham M, Ward S. 2005. Differential expression of cannabinoid receptors in the human colon: cannabinoids promote epithelial wound healing. Gastroenterology 129: 437-453.