Structural and pharmacological analysis of O-2050, a putative neutral cannabinoid CB1 receptor antagonist

European Journal of Pharmacology

Volumn 651, Issue 1-3, 2011, Pages 96-105

  Wiley, Jenny L ^a,g   Breivogel, Christopher S ^b   Mahadevan, Anu ^c   Pertwee, Roger G ^d   Cascio, Maria Grazia ^d   Bolognini, Daniele ^d,e   Huffman, John W ^f   Walentiny, D Matthew ^a   Vann, Robert E ^a   Razdan, Raj K ^c   Martin, Billy R ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b CAMPBELL UNIVERSITY   (United States)

^c ORGANIX INC   (United States)

^d UNIVERSITY OF ABERDEEN   (United Kingdom)

^e UNIVERSITY OF INSUBRIA   (Italy)

^f CLEMSON UNIVERSITY   (United States)

^g RTI INTERNATIONAL   (United States)

Author keywords

Cannabinoid; CB1 receptor; Neutral antagonist; O 2050; Structure activity relationship

Indexed keywords

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; CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID 2 RECEPTOR; CYCLIC AMP; DELTA8 TETRAHYDROCANNABINOL DERIVATIVE; DIMETHYL SULFOXIDE; DRONABINOL; FORSKOLIN; GUANOSINE 5' O (3 THIOTRIPHOSPHATE); O 2050; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTINOCICEPTION; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG ANTAGONISM; DRUG DISCRIMINATION; DRUG DOSE COMPARISON; DRUG MECHANISM; DRUG STRUCTURE; FEMALE; FOOD INTAKE; HYPOTHERMIA; IN VIVO STUDY; INHIBITION KINETICS; LOCOMOTION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; RAT; RECEPTOR BINDING; SIGNAL TRANSDUCTION; VAS DEFERENS;

ANIMALS; CYCLIC AMP; GUANOSINE 5'-O-(3-THIOTRIPHOSPHATE); MALE; MICE; PYRANS; RECEPTOR, CANNABINOID, CB1; TETRAHYDROCANNABINOL; VAS DEFERENS;

EID: 78650679418     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2010.10.085     Document Type: Article

References (41)

1. 9-Tetrahydrocannabinol discrimination in rats as a model for cannabis intoxication Neurosci. Biobehav. Rev. 16 1992 55 62
2. C.E. Bass, G. Griffin, M. Grier, A. Mahadevan, R.K. Razdan, and B.R. Martin SR-141716A-induced stimulation of locomotor activity. A structure-activity relationship study Pharmacol. Biochem. Behav. 74 2002 31 40
3. M.M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Anal. Biochem. 72 1976 248 254
4. 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
5. 35S]GTPγS binding to rat cerebellar membranes correlates with agonist-induced decreases in GDP affinity J. Biol. Chem. 273 1998 16865 16873
6. A.P. Chambers, V.K. Vemuri, Y. Peng, J.T. Wood, T. Olszewska, Q.J. Pittman, A. Makriyannis, and K.A. Sharkey A neutral CB1 receptor antagonist reduces weight gain in rat Am. J. Physiol. Regul. Integr. Comp. Physiol. 293 2007 R2185 R2193
7. 8-tetrahydrocannabinol J. Med. Chem. 33 1990 1437 1443
8. 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
9. D. Cota, G. Marsicano, B. Lutz, V. Vicennati, G.K. Stalla, R. Pasquali, and U. Pagotto Endogenous cannabinoid system as a modulator of food intake Int. J. Obes. Relat. Metab. Disord. 27 2003 289 301
10. A.A. Coutts, N. Brewster, T. Ingram, R.K. Razdan, and R.G. Pertwee Comparison of novel cannabinoid partial agonists and SR141716A in the guinea-pig small intestine Br. J. Pharmacol. 129 2000 645 652
11. P.J. Crocker, B. Saha, W.J. Ryan, J.L. Wiley, B.R. Martin, R.A. Ross, R.G. Pertwee, and R.K. Razdan Development of agonists, partial agonists and antagonists in the Δ8-tetrahydrocannabinol series Tetrahedron 55 1999 13907 13926
12. A. Gardner, and P.E. Mallet Suppression of feeding, drinking, and locomotion by a putative cannabinoid receptor 'silent antagonist' Eur. J. Pharmacol. 530 2006 103 106
13. G. Griffin, E.J. Wray, W.K. Rorrer, P.J. Crocker, W.J. Ryan, B. Saha, R.K. Razdan, B.R. Martin, and M.E. Abood An investigation into the structural determinants of cannabinoid receptor ligand efficacy Br. J. Pharmacol. 126 1999 1575 1584
14. S. Higuchi, K. Irie, S. Mishima, M. Araki, M. Ohji, A. Shirakawa, Y. Akitake, K. Matsuyama, K. Mishima, K. Mishima, K. Iwasaki, and M. Fujiwara The cannabinoid 1-receptor silent antagonist O-2050 attenuates preference for high-fat diet and activated astrocytes in mice J. Pharmacol. Sci. 112 2010 369 372
15. J.W. Huffman, J.R. Miller, J. Liddle, S. Yu, B.F. Thomas, J.L. Wiley, and B.R. Martin Structure-activity relationships for 1′, 1′- dimethylalkyl-delta8-tetrahydrocannabinols Bioorg. Med. Chem. 11 2003 1397 1410
16. R.T. Jacobs, F.J. Brown, L.A. Cronk, D. Aharony, C.K. Buckner, E.J. Kusner, K.M. Kirkland, and K.L. Neilson Substituted 3-(phenylmethyl)-1H-indole- 5-carboxamides and 1-(phenylmethyl)indole-6-carboxamides as potent, selective, orally active antagonists of the peptidoleukotrienes J. Med. Chem. 36 1993 394 409
17. T.U. Järbe, Q. Liu, and A. Makriyannis Antagonism of discriminative stimulus effects of delta(9)-THC and (R)-methanandamide in rats Psychopharmacology (Berl.) 184 2006 36 45
18. R.S. Landsman, T.H. Burkey, P. Consroe, W.R. Roeske, and H.I. Yamamura SR141716A is an inverse agonist at the human cannabinoid CB1 receptor Eur. J. Pharmacol. 334 1997 R1 R2
19. A.H. Lichtman, S.A. Varvel, and B.R. Martin Endocannabinoids in cognition and dependence Prostaglandins Leukot. Essent. Fatty Acids 66 2002 269 285
20. B.R. Martin, R. Jefferson, R. Winckler, J.L. Wiley, J.W. Huffman, P.J. Crocker, B. Saha, and R.K. Razdan Manipulation of the tetrahydrocannabinol side chain delineates agonists, partial agonists, and antagonists J. Pharmacol. Exp. Ther. 290 1999 1065 1079
21. V.G. Matassa, T.P. Maduskuie Jr., H.S. Shapiro, B. Hesp, D.W. Snyder, D. Aharony, R.D. Krell, and R.A. Keith Evolution of a series of peptidoleukotriene antagonists: synthesis and structure/activity relationships of 1, 3, 5-substituted indoles and indazoles J. Med. Chem. 33 1990 1781 1790
22. S. Mato, A. Pazos, and E.M. Valdizan Cannabinoid receptor antagonism and inverse agonism in response to SR141716A on cAMP production in human and rat brain Eur. J. Pharmacol. 443 2002 43 46
23. L.R. McMahon, B.C. Ginsburg, and R.J. Lamb Cannabinoid agonists differentially substitute for the discriminative stimulus effects of delta(9)-tetrahydrocannabinol in C57BL/6J mice Psychopharmacology (Berl.) 198 2008 487 495
24. National Research Council Guide for the Care and Use of Laboratory Animals 1996 National Academy Press Washington, D.C.
25. R.G. Pertwee Inverse agonism and neutral antagonism at cannabinoid CB1 receptors Life Sci. 76 2005 1307 1324
26. R.G. Pertwee, S.R. Fernando, G. Griffin, W. Ryan, R.K. Razdan, D.R. Compton, and B.R. Martin Agonist-antagonist characterization of 6′-cyanohex-2′-yne-delta-8-tetrahydrocannabinol in two isolated tissue preparations Eur. J. Pharmacol. 315 1996 195 201
27. R.G. Pertwee, R.A. Ross, S.J. Craib, and A. Thomas (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens Eur. J. Pharmacol. 456 2002 99 106
28. 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
29. M. Rinaldi-Carmona, F. Barth, M. Heaulme, R. Alonso, D. Shire, C. Congy, P. Soubrie, J.C. Breliere, and G. Le Fur Biochemical and pharmacological characterisation of SR141716A, the first potent and selective brain cannabinoid receptor antagonist Life Sci. 56 1995 1941 1947
30. K. Sano, E. Koushi, K. Irie, S. Higuchi, R. Tsuchihashi, J. Kinjo, N. Egashira, R. Oishi, N. Uchida, H. Nagai, R. Nishimura, H. Tanaka, S. Morimoto, K. Mishima, K. Iwasaki, and M. Fujiwara Delta(9)-tetrahydrocannabinol enhances an increase of plasma corticosterone levels induced by forced swim-stress Biol. Pharm. Bull. 32 2009 2065 2067
31. D.E. Selley, S. Stark, L.J. Sim, and S.R. Childers Cannabinoid receptor stimulation of guanosine-5′-O-(3-[35S]thio)triphosphate binding in rat brain membranes Life Sci. 59 1996 659 668
32. M. Singer, W.J. Ryan, B. Saha, B.R. Martin, and R.K. Razdan Potent cyano and carboxamide side-chain analogus of 1′, 1′-dimethyl-Δ8- tetrahydrocannabinol J. Med. Chem. 41 1998 4400 4407
33. M. Solinas, S.R. Goldberg, and D. Piomelli The endocannabinoid system in brain reward processes Br. J. Pharmacol. 154 2008 369 383
34. A. Thomas, R.A. Ross, B. Saha, A. Mahadevan, R.K. Razdan, and R.G. Pertwee 6″-Azidohex-2″-yne-cannabidiol: a potential neutral, competitive cannabinoid CB1 receptor antagonist Eur. J. Pharmacol. 487 2004 213 221
35. R.E. Vann, J.A. Warner, K. Bushell, J.W. Huffman, B.R. Martin, and J.L. Wiley Discriminative stimulus properties of delta9-tetrahydrocannabinol (THC) in C57Bl/6 J mice Eur. J. Pharmacol. 615 2009 102 107
36. S.P. Welch, J.W. Huffman, and J. Lowe Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR141716A J. Pharmacol. Exp. Ther. 286 1998 1301 1308
37. J.L. Wiley, J.A. Lowe, R.L. Balster, and B.R. Martin Antagonism of the discriminative stimulus effects of delta 9-tetrahydrocannabinol in rats and rhesus monkeys J. Pharmacol. Exp. Ther. 275 1995 1 6
38. J.L. Wiley, D.R. Compton, P.M. Gordon, C. Siegel, M. Singer, A. Dutta, A.H. Lichtman, R.L. Balster, R.K. Razdan, and B.R. Martin Evaluation of agonist-antagonist properties of nitrogen mustard and cyano derivatives of delta 8-tetrahydrocannabinol Neuropharmacology 35 1996 1793 1804
39. J.L. Wiley, G.S. Patrick, P.C. Crocker, B. Saha, R.K. Razdan, and B.R. Martin Antinociceptive effects of tetrahydrocannabinol side chain analogs: dependence upon route of administration Eur. J. Pharmacol. 397 2000 319 326
40. J.L. Wiley, R.G. Jefferson, G. Griffin, J. Liddle, S. Yu, J.W. Huffman, and B.R. Martin Paradoxical pharmacological effects of deoxy- tetrahydrocannabinol analogs lacking high CB1 receptor affinity Pharmacology 66 2002 89 99
41. J.L. Wiley, J.J. Burston, D.C. Leggett, O.O. Alekseeva, R.K. Razdan, A. Mahadevan, and B.R. Martin CB1 cannabinoid receptor-mediated modulation of food intake in mice Br. J. Pharmacol. 145 2005 293 300