International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors

  title={International Union of Pharmacology. XXVII. Classification of Cannabinoid Receptors},
  author={Allyn C. Howlett and Francis Barth and Tom I. Bonner and G. Cabral and Pierre Casellas and William A. Devane and Christian C. Felder and Miles Herkenham and Ken Mackie and Billy R. Martin and Raphael Mechoulam and Roger G. Pertwee},
  journal={Pharmacological Reviews},
  pages={161 - 202}
Two types of cannabinoid receptor have been discovered so far, CB1 (2.1: CBD:1:CB1:), cloned in 1990, and CB2(2.1:CBD:2:CB2:), cloned in 1993. Distinction between these receptors is based on differences in their predicted amino acid sequence, signaling mechanisms, tissue distribution, and sensitivity to certain potent agonists and antagonists that show marked selectivity for one or the other receptor type. Cannabinoid receptors CB1 and CB2 exhibit 48% amino acid sequence identity. Both receptor… 

The pharmacology of cannabinoid receptors and their ligands: an overview

  • R. Pertwee
  • Biology, Medicine
    International Journal of Obesity
  • 2006
Mammalian tissues express at least two cannabinoid receptor types, CB1 and CB2, both G protein coupled. CB1 receptors are found predominantly at nerve terminals where they mediate inhibition of

Recent advances in the development of selective ligands for the cannabinoid CB(2) receptor.

This review will discuss the current advances and recent results in the structure-activity relationships (SAR) of selective ligands for the cannabinoid CB(2) receptor.

Pharmacological actions of cannabinoids.

  • R. Pertwee
  • Biology, Chemistry
    Handbook of experimental pharmacology
  • 2005
More information is beginning to emerge about the pharmacological actions of the non-psychoactive plant cannabinoid, cannabidiol, as well as acting on CB1 and CB2 receptors, and there is convincing evidence that anandamide can activate transient receptor potential vanilloid type 1 (TRPV1) receptors.

Cannabinoid receptors: nomenclature and pharmacological principles

Therapeutic utility of cannabinoid receptor type 2 (CB(2)) selective agonists.

It is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects, and high value putative therapeutics for treating pain and other disease states are represented.

A study of functional selectivity at the cannabinoid type 1 receptor

This thesis investigates ligand-selective functional selectivity at the cannabinoid CB1 receptor both endogenously and exogenously expressed in a variety of cell lines and results suggest it may be possible to produce drugs which selectively activate signalling pathways linked to therapeutic benefits, while minimising activation of those associated with unwanted side effects.

The cannabinoid receptors.

  • A. Howlett
  • Biology, Chemistry
    Prostaglandins & other lipid mediators
  • 2002

Endocannabinoids: biology, mechanism of action and functions

  • K. Sharkey
  • Biology, Medicine
    International Journal of Obesity
  • 2006
The isolation and identification of endogenous cannabinoid ligands (endocannabinoids) as a family of intercellular signaling molecules that act at the same receptors as the plant-derived cannabinoids

Cannabinoid Receptors: Where They are and What They do

  • K. Mackie
  • Biology
    Journal of neuroendocrinology
  • 2008
The endocannabinoid system consists of the endogenous cannabinoids (endocannabinoids), cannabinoid receptors and the enzymes that synthesise and degrade endOCannabinoids, although additional receptors may be involved, and partial agonism, functional selectivity and inverse agonism all play important roles in determining the cellular response to specific cannabinoid receptor ligands.

CB1 and CB2 Receptor Pharmacology.




Pharmacology of cannabinoid receptor ligands.

  • R. Pertwee
  • Biology, Chemistry
    Current medicinal chemistry
  • 1999
This review summarizes current knowledge about the in vitro pharmacological properties of important CB1 and CB2 receptor ligands and pays particular attention to the binding properties of these ligands, to the efficacies of cannabinoid receptor agonists, as determined using cyclic AMP or [35S]GTPgammaS binding assays, and to selected examples of how these pharmacological Properties can be influenced by chemical structure.

Molecular aspects of cannabinoid receptors.

  • L. Matsuda
  • Biology
    Critical reviews in neurobiology
  • 1997
Although receptors appear to be involved in cannabimimetic-induced modulation of immune cell function, the receptor subtype that is principally involved in specific effects is difficult to determine because both receptors are often coexpressed in the same cells.

Pharmacology of cannabinoid CB1 and CB2 receptors.

  • R. Pertwee
  • Biology, Medicine
    Pharmacology & therapeutics
  • 1997

Evaluation of binding in a transfected cell line expressing a peripheral cannabinoid receptor (CB2): identification of cannabinoid receptor subtype selective ligands.

Although most of the chosen compounds did not discriminate between CB1 and CB2, several ligands were identified that showed selectivity and can now serve as a basis for the design of compounds with even greater selectivity.

Cannabinoid receptors and their endogenous agonists.

Progress is being made in the development of novel agonists and antagonists with receptor subtype selectivity, mice with genetic deletion of the cannabinoid receptors, and receptor-specific antibodies, which should help in providing a better understanding of the physiological role of the cannabinoids.

Cannabinoid receptor expression in immune cells.

RT-PCR is a highly sensitive and discriminatory measure of cannabinoid receptor type-specific gene expression, Nevertheless, this technique suffers from several potential deficiencies especially when used to study intron-less genes such as those for CB 1 and CB2 where genomic DNA (gDNA) amplification products would have the same size as products derived from cDNA.

Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors.

Except for its inability to couple to the modulation of Q-type calcium channels or inwardly rectifying potassium channels, the CB1 and CB2 receptors display similar pharmacological and biochemical properties.

Behavioral effects of cannabinoid agents in animals.

In animals, cannabinoid agonists such as delta9-THC, WIN 55,212-2, and CP 55,940 produce a characteristic combination of four symptoms, hypothermia, analgesia, hypoactivity, and catalepsy, providing good evidence for the involvement of CB1-related mechanisms.

The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt.

It is shown here that Delta(9)-tetrahydrocannabinol (THC), the major active component of marijuana, induces the activation of protein kinase B/Akt (PKB), and data indicate that activation of PKB may be responsible for some of the effects of cannabinoids in cells expressing the CB(1) receptor.