JPET Assistant Professor of Medicine (Clinician-Educator)

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hillard, C. J.
Right arrow Articles by Campbell, W. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hillard, C. J.
Right arrow Articles by Campbell, W. B.

Vol. 289, Issue 3, 1427-1433, June 1999

Synthesis and Characterization of Potent and Selective Agonists of the Neuronal Cannabinoid Receptor (CB1)1

Cecilia J. Hillard, Sukumar Manna, Marcie J. Greenberg, Ralph DiCamelli, Ruth A. Ross, Lesley A. Stevenson, Vicki Murphy, Roger G. Pertwee and William B. Campbell

Department of Pharmacology and Toxicology (C.J.H., S.M., M.J.G., R.D., W.B.C.), Medical College of Wisconsin, Milwaukee, Wisconsin; and Department of Biomedical Sciences (R.A.R., L.A.S., V.M., R.G.P.), University of Aberdeen, Aberdeen, Scotland

Two subtypes of the cannabinoid receptor (CB1 and CB2) are expressed in mammalian tissues. Although selective antagonists are available for each of the subtypes, most of the available cannabinoid agonists bind to both CB1 and CB2 with similar affinities. We have synthesized two analogs of N-arachidonylethanolamine (AEA), arachidonylcyclopropylamide (ACPA) and arachidonyl-2-chloroethylamide (ACEA), that bind to the CB1 receptor with very high affinity (KI values of 2.2 ± 0.4 nM and 1.4 ± 0.3 nM, respectively) and to the CB2 receptor with low affinity (KI values of 0.7 ± 0.01 µM and 3.1 ± 1.0 µM, respectively). Both ACPA and ACEA have the characteristics of agonists at the CB1 receptor; both inhibit forskolin-induced accumulation of cAMP in Chinese hamster ovary cells expressing the human CB1 receptor, and both analogs increase the binding of [35S]GTPgamma S to cerebellar membranes and inhibit electrically evoked contractions of the mouse vas deferens. ACPA and ACEA produce hypothermia in mice, and this effect is inhibited by coadministration of the CB1 receptor antagonist SR141716A. Therefore, ACPA and ACEA are high-affinity agonists of the CB1 receptor but do not bind the CB2 receptor, suggesting that structural analogs of AEA can be designed with considerable selectivity for the CB1 receptor over the CB2 receptor.

0022-3565/99/2893-1427$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 J. Neurophysiol.Home page
C. Potenzieri, T. S. Brink, C. Pacharinsak, and D. A. Simone
Cannabinoid Modulation of Cutaneous A{delta} Nociceptors During Inflammation
J Neurophysiol, November 1, 2008; 100(5): 2794 - 2806.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Paradisi, N. Pasquariello, D. Barcaroli, and M. Maccarrone
Anandamide Regulates Keratinocyte Differentiation by Inducing DNA Methylation in a CB1 Receptor-dependent Manner
J. Biol. Chem., March 7, 2008; 283(10): 6005 - 6012.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Esposito, T. Iuvone, C. Savani, C. Scuderi, D. De Filippis, M. Papa, V. Di Marzo, and L. Steardo
Opposing Control of Cannabinoid Receptor Stimulation on Amyloid-beta-Induced Reactive Gliosis: In Vitro and in Vivo Evidence
J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1144 - 1152.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
E. Sanchez-Pastor, X. Trujillo, M. Huerta, and F. Andrade
Effects of Cannabinoids on Synaptic Transmission in the Frog Neuromuscular Junction
J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 439 - 445.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
L. R. McMahon
Characterization of Cannabinoid Agonists and Apparent pA2 Analysis of Cannabinoid Antagonists in Rhesus Monkeys Discriminating {Delta}9-Tetrahydrocannabinol
J. Pharmacol. Exp. Ther., December 1, 2006; 319(3): 1211 - 1218.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
P. Pacher, S. Batkai, and G. Kunos
The Endocannabinoid System as an Emerging Target of Pharmacotherapy
Pharmacol. Rev., September 1, 2006; 58(3): 389 - 462.
[Abstract] [Full Text] [PDF]

Home page
 Alcohol AlcoholHome page
F. RODRIGUEZ de FONSECA, I. DEL ARCO, F. J. BERMUDEZ-SILVA, A. BILBAO, A. CIPPITELLI, and M. NAVARRO
THE ENDOCANNABINOID SYSTEM: PHYSIOLOGY AND PHARMACOLOGY
Alcohol Alcohol., January 1, 2005; 40(1): 2 - 14.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Leterrier, D. Bonnard, D. Carrel, J. Rossier, and Z. Lenkei
Constitutive Endocytic Cycle of the CB1 Cannabinoid Receptor
J. Biol. Chem., August 20, 2004; 279(34): 36013 - 36021.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
E. J. Carrier, C. S. Kearn, A. J. Barkmeier, N. M. Breese, W. Yang, K. Nithipatikom, S. L. Pfister, W. B. Campbell, and C. J. Hillard
Cultured Rat Microglial Cells Synthesize the Endocannabinoid 2-Arachidonylglycerol, Which Increases Proliferation via a CB2 Receptor-Dependent Mechanism
Mol. Pharmacol., April 1, 2004; 65(4): 999 - 1007.
[Abstract] [Full Text]

Home page
 Toxicol SciHome page
Y. Segall, G. B. Quistad, S. E. Sparks, D. K. Nomura, and J. E. Casida
Toxicological and Structural Features of Organophosphorus and Organosulfur Cannabinoid CB1 Receptor Ligands
Toxicol. Sci., November 1, 2003; 76(1): 131 - 137.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
T. W. Klein, C. Newton, K. Larsen, L. Lu, I. Perkins, L. Nong, and H. Friedman
The cannabinoid system and immune modulation
J. Leukoc. Biol., October 1, 2003; 74(4): 486 - 496.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
T. F. FREUND, I. KATONA, and D. PIOMELLI
Role of Endogenous Cannabinoids in Synaptic Signaling
Physiol Rev, July 1, 2003; 83(3): 1017 - 1066.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. H. Lichtman, E. G. Hawkins, G. Griffin, and B. F. Cravatt
Pharmacological Activity of Fatty Acid Amides Is Regulated, but Not Mediated, by Fatty Acid Amide Hydrolase in Vivo
J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 73 - 79.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
A. C. Howlett, F. Barth, T. I. Bonner, G. Cabral, P. Casellas, W. A. Devane, C. C. Felder, M. Herkenham, K. Mackie, B. R. Martin, et al.
International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors
Pharmacol. Rev., June 1, 2002; 54(2): 161 - 202.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
S. Kelly and V. Chapman
Selective Cannabinoid CB1 Receptor Activation Inhibits Spinal Nociceptive Transmission In Vivo
J Neurophysiol, December 1, 2001; 86(6): 3061 - 3064.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. O. P. Jacobsson, T. Wallin, and C. J. Fowler
Inhibition of Rat C6 Glioma Cell Proliferation by Endogenous and Synthetic Cannabinoids. Relative Involvement of Cannabinoid and Vanilloid Receptors
J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 951 - 959.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
S. Patel and C. J. Hillard
Cannabinoid CB1 Receptor Agonists Produce Cerebellar Dysfunction in Mice
J. Pharmacol. Exp. Ther., April 12, 2001; 297(2): 629 - 637.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1999 by the American Society for Pharmacology and Experimental Therapeutics.