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.