In Vitro Binding Assays

Several cannabinoid receptor ligands have been radiolabelled with tritium, and these have been usedboth to determine the CB1 and CB2 receptor affinities of unla-belled cannabinoids in displacement assays and to establish the tissue distribution patterns of these receptors (reviewed in Howlett et al. 2002 Pertwee 1999a). As indicated in Tables 1,2 and 3, some of these compounds bind more readily to CBi or to CB2 receptors, whilst the others bind more or less equally well to both these Table 1....

Cannabinoid CB1 and CB2 Receptor Antagonists 321

The first selective CB1 receptor antagonist, the diarylpyrazole SR141716A (Fig. 10), was developed by Sanofi Recherche (Rinaldi-Carmonaetal. 1994). This readily prevents or reverses effects induced by cannabinoids at CB1 receptors, both in vitro and in vivo (reviewed in Howlett et al. 2002 Pertwee 1997). It binds with significantly higher affinity to CB1 than CB2 receptors (Table 3), lacks significant affinity for a wide range of non-cannabinoid receptors and does not exhibit detectable agonist...

Neuronal NonCB1 NonCB2 NonTRPV1 Receptors

Central G Protein-Coupled Receptors for Anandamide and R-(+)-WIN55212 Evidence for the presence of a G protein-coupled non-CB1, non-CB2 receptor for anandamide and R-(+)-WIN55212 has come from experiments in which it was found that 35S GTPyS binding to whole-brain membranes from CB1- - C57BL 6 mice or to cerebellar homogenates from CB1- - CD1 mice could be enhanced by these two cannabinoids (Breivogel et al. 2001 Di Marzo et al. 2000 Monory et al. 2002). Near maximal concentrations of...

Isolated Nerve Smooth Muscle Preparations

Preparations in which cannabinoid receptor agonists can act through neuronal CB1 receptors to produce a concentration-related inhibition both of electrically-evoked contractile transmitter release (Schlicker et al. 2003 Trendelenburg et al. 2000) and of the contractions caused by this release (reviewed in Howlett et al. 2002 Pertwee 1997 Pertwee et al. 1996a Schlicker and Kathmann 2001) are called isolated nerve-smooth muscle preparations. The ones most commonly used are the mouse vas deferens...

Introduction

Liver Cancer Planting Transfer

Cannabinoid was originally the collective name given to a set of oxygen-containing C21 aromatic hydrocarbon compounds that occur naturally in the plant Cannabis sativa (ElSohly 2002 Mechoulam and Gaoni 1967). However, this term is now generally also used for all naturally occurring or synthetic compounds that can mimicthe actions of plant-derived cannabinoids or thathave structures that closely resemble those of plant cannabinoids. Consequently, a separate term, phyto-cannabinoid, has been...

Receptors for Abnormal Cannabidiol

There is evidence, mainly from in vitro experiments with rat or mouse phenylephrine- or methoxamine-precontracted buffer-perfused isolated mesenteric arterial beds or isolated mesenteric arterial segments, for the presence in these tissues of non-CB1, non-CB2 receptors with which anandamide and methanandamide can interact to induce a relaxant effect (reviewed in Howlett et al. 2002 Pertwee 2004a Wiley and Martin 2002). There are several reasons for believing that these are not CB1 or CB2...

Cannabinoid Receptor Agonists

Cannabinoid Examples

In terms of chemical structure, established cannabinoid receptor agonists fall essentially into four main groups classical, nonclassical, aminoalkylindole and eicosanoid (reviewed in Howlett et al. 2002 Pertwee 1999a). - The classical group consists of dibenzopyran derivatives that are either cannabis-derived compounds (phytocannabinoids) or their synthetic analogues. Notable examples are the phytocannabinoids49-THC,48-THC and cannabinol (Fig. 1), and the synthetic cannabinoids, JWH-133,...