Cannabinoid Receptors
Cannabinoid receptors are currently classified into three groups: central (CB1), peripheral (CB2) and GPR55, all of which are G-protein-coupled.
Related Targets
Cannabinoid Transporters | Monoacylglycerol Lipase (MAGL) |
Fatty Acid Amide Hydrolase (FAAH) | Non-selective Cannabinoids |
Fatty Acid Binding Proteins (FABP) | Other Cannabinoids |
GPR55 (GPR55) | TRPV Channels (TRPV Channels) |
CB1 receptors are primarily located at central and peripheral nerve terminals. CB2 receptors are predominantly expressed in non-neuronal tissues, particularly immune cells, where they modulate cytokine release and cell migration. Recent reports have suggested that CB2 receptors may also be expressed in the CNS. GPR55 receptors are non-CB1/CB2 receptors that exhibit affinity for endogenous, plant and synthetic cannabinoids. Endogenous ligands for cannabinoid receptors have been discovered, including anandamide and 2-arachidonylglycerol.
Cannabinoid Receptor Data
| Receptor Subtype | CB1 | CB2 | GPR55 |
|---|---|---|---|
| Transduction Mechanism | ↓Adenylyl Cyclase (Gi/o), ↓ N- and P/Q-type Ca2+ currents, ↑ Kir and A-types K+ currents | ↓ Adenylyl Cyclase (Gi/o) | Activation of Rho family GTPases |
| Primary Distribution | CNS: hippocampus, basal ganglia, cerebellum, cortex, globus pallidus, substantia nigra, pars reticulata | Spleen, tonsils, immune cells | CNS: caudate and putamen |
| Tissue Function | Modulation of neurotransmitter release | Suppression of immune cell function | Pain signaling, control of vascular tone, inflammation |
| Key Compounds | Ki Values (nM) at CB1 | Ki Values (nM) at CB2 | |
|---|---|---|---|
| Endogenous Agonists | Anandamide (1339) 2-Arachidonylglycerol (1298) NADA (1568) Noladin ether (1411) | 61-543 58.3-472 2501 21.2 | 279-1940 145-1400 12001 > 3000 |
| Key CB1 Agonists | ACEA (1319) ACPA (1318) (R)-(+)-Methanandamide (1121) | 1.4 2.2 17.9-28.3 | > 2000 715 815-868 |
| Key CB2 Agonists | CB 65 (2663) GP 1a (2764) GP 2a (2678) GW 405833 (2374)* JWH 015 (1341) JWH 133 (1343) L-759,656 (2434) L-759,633 (2433) | > 1000 363 900 4772 383 677 4888 1043 | 3.3 0.037 7.6 3.92 13.8 3.4 11.8 6.4 |
| Non-selective Agonists | CP 55,940 (0949) HU 210 (0966) O-2545 (2680) WIN 55,212-2 (1038) Bay 59-3074 (2500) Δ9-Tetrahydrocannabinol | 0.5-5.0 0.06-0.73 1.5 5.05 1.89-123 48.3 5.05 | 0.69-2.8 0.17-0.52 0.32 3.13 0.28-16.2 45.5 3.13 |
| Key CB1 Antagonists/ Inverse Agonists | AM 251 (1117) AM 281 (1115) LY 320135 (2387) | 7.49 12 141 | 2290 4200 14900 |
| Key CB2 Antagonists/ Inverse Agonists | AM 630 (1120) | 5152 | 31.2 |
*partial agonist
References
Bisogno et al (2000) N-acyl-dopamines: novel synthetic CB1 cannabinoid-receptor ligands and inhibitors of anandamide inactivation with cannabimimetic activity in vitro and in vivo. Biochem.J. 351 817. Pertwee (2006) Cannabinoid receptor ligands. Tocris Reviews No. 27.Manera et al (2006) Design, synthesis, and biological evaluation of new 1,8-naphthyridin-4(1H)-on-3-carboxamide and quinolin-4(1H)-on-3-carboxamide derivatives as CB2 selective agonists. J.Med.Chem. 49 5947. Murineddu et al (2006) Tricyclic pyrazoles. 4. Synthesis and biological evaluation of analogues of the robust and selective CB2 cannabinoid ligand 1-(2',4'-dichlorophenyl)-6-methyl-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide. J.Med.Chem. 49 7502. Ross et al (1999) Agonist-inverse agonist characterization at CB1 and CB2 cannabinoid receptors of L759633, L759656 and AM630. Br.J.Pharmacol. 126 665. Martin et al (2006) Pharmacological characterization of novel water-soluble cannabinoids. J.Pharmacol.Exp.Ther. 318 1230. Pertwee (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. Br.J.Pharmacol. 153 199.