6″-Azidohex-2″-yne-cannabidiol: A potential neutral, competitive cannabinoid CB1 receptor antagonist

European Journal of Pharmacology

Volumn 487, Issue 1-3, 2004, Pages 213-221

  Thomas, Adèle ^a   Ross, Ruth A ^a   Saha, Bijali ^b   Mahadevan, Anu ^b   Razdan, Raj K ^b   Pertwee, Roger G ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b ORGANIX INC   (United States)

Author keywords

Abnormal cannabidiol; Cannabidiol; Cannabinoid CB1 receptor; Mouse vas deferens; Novel cannabinoid receptor antagonist; WIN55212

Indexed keywords

2' MONOMETHOXYCANNABIDIOL; 2',6' DIMETHOXYCANNABIDIOL; 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; 6'' AZIDOHEX 2'' YNE CANNABIDIOL; CANNABIDIOL; CANNABIDIOL DERIVATIVE; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID 1 RECEPTOR ANTAGONIST; CANNABINOID RECEPTOR AGONIST; CANNABINOID RECEPTOR ANTAGONIST; O 2654; O 2796; O 2797; UNCLASSIFIED DRUG; 5' ADENYLYL (BETA,GAMMA METHYLENE)DIPHOSPHONATE; 5'-ADENYLYL (BETA,GAMMA-METHYLENE)DIPHOSPHONATE; 6''-AZIDOHEX-2''-YNE-CANNABIDIOL; ADENOSINE TRIPHOSPHATE; ALPHA ADRENERGIC RECEPTOR STIMULATING AGENT; CANNABINOID 1 RECEPTOR; CYCLOHEXANOL DERIVATIVE; DRUG DERIVATIVE; PHENYLEPHRINE;

ANIMAL TISSUE; ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG BINDING; DRUG EFFECT; DRUG POTENCY; DRUG STRUCTURE; DRUG TARGETING; EVOKED RESPONSE; FEMALE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; VAS DEFERENS; ANIMAL; BINDING COMPETITION; BRAIN LEVEL; DRUG ANTAGONISM; ELECTROSTIMULATION; IN VITRO STUDY; MEMBRANE;

ADENOSINE TRIPHOSPHATE; ADRENERGIC ALPHA-AGONISTS; ANIMALS; BINDING, COMPETITIVE; BRAIN CHEMISTRY; CANNABIDIOL; CYCLOHEXANOLS; ELECTRIC STIMULATION; MALE; MEMBRANES; MICE; PHENYLEPHRINE; RECEPTOR, CANNABINOID, CB1; VAS DEFERENS;

EID: 1642342100     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2004.01.023     Document Type: Article

References (28)

1. Breivogel C.S., Griffin G., Di Marzo V., Martin B.R. Evidence for a new G protein-coupled cannabinoid receptor in mouse brain. Mol. Pharmacol. 60:2001;155-163.
2. 50) of an enzymatic reaction. Biochem. Pharmacol. 22:1973;3099-3108.
3. Clark A.L., Mitchelson F. The inhibitory effect of gallamine on muscarinic receptors. Br. J. Pharmacol. 58:1976;323-331.
4. Compton D.R., Rice K.C., de Costa B.R., Razdan R.K., Melvin L.S., Johnson M.R., Martin B.R. Cannabinoid structure-activity relationships: correlation of receptor binding and in vivo activities. J. Pharmacol. Exp. Ther. 265:1993;218-226.
5. Consroe P., Musty R., Rein J., Tillery W., Pertwee R. The perceived effects of smoked cannabis on patients with multiple sclerosis. Eur. Neurol. 38:1997;44-48.
6. Felder C.C., Joyce K.E., Briley E.M., Glass M., Mackie K.P., Fahey K.J., Cullinan G.J., Hunden D.C., Johnson D.W., Chaney M.O., Koppel G.A., Brownstein M. LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation. J. Pharmacol. Exp. Ther. 284:1998;291-297.
7. Hájos N., Freund T.F. Pharmacological separation of cannabinoid sensitive receptors on hippocampal excitatory and inhibitory fibers. Neuropharmacology. 43:2002;503-510.
8. 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.
9. Járai Z., Wagner J.A., Varga K., Lake K.D., Compton D.R., Martin B.R., Zimmer A.M., Bonner T.I., Buckley N.E., Mezey E., Razdan R.K., Zimmer A., Kunos G. Cannabinoid-induced mesenteric vasodilation through an endothelial site distinct from CB1 or CB2 receptors. Proc. Natl. Acad. Sci. U. S. A. 96:1999;14136-14141.
10. Kenakin T. Pharmacologic Analysis of Drug-Receptor Interaction. Third edition:1997;Lippincott-Raven, Philadelphia.
11. Offertáler L., Mo F.-M., Bátkai S., Liu J., Begg M., Razdan R.K., Martin B.R., Bukoski R.D., Kunos G. Selective ligands and cellular effectors of a G protein-coupled endothelial cannabinoid receptor. Mol. Pharmacol. 63:2003;699-705.
12. Pertwee R.G. The central neuropharmacology of psychotropic cannabinoids. Pharmacol. Ther. 36:1988;189-261.
13. 2 receptors. Pharmacol. Ther. 74:1997;129-180.
14. Pertwee R.G. The pharmacology and therapeutic potential of cannabidiol. Di Marzo V. Cannabinoids. 2004;Landes Bioscience, Georgetown. In press.
15. Pertwee R.G. Inverse agonism at cannabinoid receptors. Ijzerman A.P. Inverse Agonism, Esteve Foundation Symposia. vol. 10:2003;75-86 Excerpta Medica, Amsterdam.
16. Pertwee R.G., Griffin G., Lainton J.A.H., Huffman J.W. Pharmacological characterization of three novel cannabinoid receptor agonists in the mouse isolated vas deferens. Eur. J. Pharmacol. 284:1995;241-247.
17. 8-tetrahydrocannabinol in two isolated tissue preparations. Eur. J. Pharmacol. 315:1996;195-201.
18. Pertwee R.G., Ross R.A., Craib S.J., Thomas A. (-)-Cannabidiol antagonizes cannabinoid receptor agonists and noradrenaline in the mouse vas deferens. Eur. J. Pharmacol. 456:2002;99-106.
19. 8- tetrahydrocannabinol at cannabinoid receptors. Br. J. Pharmacol. 128:1999;735-743.
20. Ross R.A., Gibson T.M., Brockie H.C., Leslie M., Pashmi G., Craib S.J., Di Marzo V., Pertwee R.G. Structure-activity relationship for the endogenous cannabinoid, anandamide, and certain of its analogues at vanilloid receptors in transfected cells and vas deferens. Br. J. Pharmacol. 132:2001;631-640.
21. Schlicker E., Kathman M. Modulation of transmitter release via presynaptic cannabinoid receptors. Trends Pharmacol. Sci. 22:2001;565-572.
22. 1 receptors increases noradrenaline release in vas deferens without affecting atrial noradrenaline release or cortical acetylcholine release. Br. J. Pharmacol. 140:2003;323-328.
23. Showalter V.M., Compton D.R., Martin B.R., Abood M.E. 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.
24. Thomas B.F., Gilliam A.F., Burch D.F., Roche M.J., Seltzman H.H. Comparative receptor binding analyses of cannabinoid agonists and antagonists. J. Pharmacol. Exp. Ther. 285:1998;285-292.
25. Thomas A., Ross R.A., Razdan R.K., Saha B., Mahadevan A., Pertwee R. Structural determinants of pharmacological actions of cannabidiol in the mouse isolated vas deferens. Symposium on the Cannabinoids Burlington, Vermont, International Cannabinoid Research Society. 2003;5.
26. 3H-noradrenaline release by presynaptic opioid, cannabinoid and bradykinin receptors and β-adrenoceptors in mouse tissues. Br. J. Pharmacol. 130:2000;321-330.
27. von Kügelgen I., Starke K. Noradrenaline-ATP co-transmission in the sympathetic nervous system. Trends Pharmacol. Sci. 12:1991;319-324.
28. Whittle B.A., Guy G.W., Robson P. Prospects for new cannabis-based prescription medicines. J. Cannabis Ther. 1:2001;183-205.