Cannabinoid Receptors

Cannabinoid receptors are currently classified into three groups: central (CB1), peripheral (CB2) and GPR55, all of which are G-protein-coupled.

Targets
Literature
Receptor Data

Cannabinoid Receptor Target Files

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.

Literature for Cannabinoid Receptors

GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Neurodegeneration

Neurodegeneration Product Guide

A collection of over 275 products for neurodegeneration research, the guide includes research tools for the study of:

  • Alzheimer's disease
  • Parkinson's disease
  • Huntington's disease
Pain

Pain Research Product Guide

A collection of over 250 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
Cannabinoid Receptor Ligands

Cannabinoid Receptor Ligands Scientific Review

Written by Roger Pertwee, this review discusses compounds which affect the activity of the endocannabinoid system, focusing particularly on ligands that are most widely used as experimental tools and denotes compounds available from Tocris.

Pain

Pain Poster

Peripheral sensitization is the reduction in the threshold of excitability of sensory neurons that results in an augmented response to a given external stimulus. This poster outlines the excitatory and inhibitory signaling pathways involved in modulation of peripheral sensitization. The role of ion channels, GPCRs, neurotrophins, and cytokines in sensory neurons are also described.

Schizophrenia

Schizophrenia Poster

Schizophrenia is a debilitating psychiatric disorder that affects 1% of the worldwide population. This poster describes the neurobiology of Schizophrenia, as well as highlighting the genetic and environmental factors that play a fundamental role in the etiology of the disease. The current and emerging drug targets are also discussed.

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.