Cannabinoid Receptor Ligands
neuronal transporters of dopamine, noradrenaline
JTE 907, CB 2 -Selective
and 5-hydroxytryptamine (Table 3), and that there are
Inverse Agonist
a number of less sensitive pharmacological targets
for 9 -THC and/or for certain other cannabinoid
receptor agonists. These targets, which only seem to
Cat. No. 2479
respond to cannabinoid concentrations above 1 µ M,
include L-type Ca 2+ and shaker Kv1.2 K + channels,
PPAR γ and TRPA1 receptors, putative non-CB 1 ,
non-CB 2 , non-TRPV1 neuronal receptors in the small
JTE 907 is a highly selective CB 2 receptor inverse agonist.
intestine, sites on muscarinic M 1 and M 4 receptors
It binds with high affinity to rat, mouse and human CB 2
and on glutamate GLU A1 and GLU A3 receptors,
receptors (K i values are 0.38, 1.55 and 35.9 nM respectively)
and produces anti-inflammatory effects in vivo .
and sites at gap junctions between cells. 2,86,88,94,95
Anandamide and methanandamide, but not 9 -THC,
Iwamura et al (2001) In vitro and in vivo pharmacological characterization of
JTE-907, a novel selective ligand for cannabinoid CB 2 receptor. J.Pharmacol.
Exp.Ther. 296 420. Ueda et al (2005) Involvement of cannabinoid CB 2 receptor-
as agonists for the putative abnormal-cannabidiol
mediated response and efficacy of cannabinoid CB 2 receptor inverse agonist,
JTE-907, in cutaneous inflammation in mice. Eur.J.Pharmacol. 520 164.
(abnormal-CBD) receptor 2,88,96 (see also section on
Maekawa et al (2006) The cannabinoid CB 2 receptor inverse agonist JTE-907
other notable ligands).
suppresses spontaneous itch-associated responses of NC mice, a model of
atopic dermatitis. Eur.J.Pharmacol. 542 179.
The CB 1 receptor antagonists/inverse agonists,
SR141716A and AM 251, can also interact with non-
[ 3 H]CP 55,940, [ 3 H]WIN 55,212-2 and [ 3 H]HU 243
CB 1 , non-CB 2 targets, albeit only at concentrations
are 0.07 to 4 nM, 1.9 to 16.2 nM and 0.045 nM
that lie in the micromolar range and hence above
respectively at CB 1 receptors and 0.2 to 7.4 nM, 2.1 to
concentrations at which these ligands are capable of
3.8 nM and 0.061 nM respectively at CB 2 receptors. 2,41
producing significant CB 1 receptor antagonism. Thus
Thus [ 3 H]HU 243, which is structurally very similar to
for example, as also discussed elsewhere, 74,88 there
HU 210 (Figure 1), has particularly high affinity for
are reports that at micromolar concentrations:
these receptors. Radiolabelled ligands have also
been developed as potential probes for human single
  • SR141716A and AM 251 can block adenosine A 1
  • photon emission computed tomography (SPECT) or
    receptor activation,
    positron emission tomography (PET) experiments.
  • AM 251 can block neuronal voltage-sensitive Na +
  • These are 123 I labelled analogues of AM 251
    (CB 1 K d = 0.23 to 0.62 nM) and AM 281 81-83 and an
    18 F-labelled analogue of SR141716A (SR144385). 84
  • SR141716A can block L-type Ca 2+ channels,
  • Particularly promising results have been obtained
    Ca 2+ -activated (BK) K + channels, ATP-sensitive
    from animal experiments with [ 123 I]AM 281. 82,85
    K + channels and sites at gap junctions between
    Additional Pharmacological Targets
  • SR141716A can block the activation of putative
  • for CB 1 and CB 2 Receptor Ligands
    abnormal-CBD receptors on mesenteric arteries
    cannabinoid receptor agonists are reasonably
    potent at activating the TRPV1 (vanilloid VR1)
    AM 630, Competitive
    receptor (Table 3). These include eicosanoids
    CB 2 Antagonist
    and the putative endocannabinoid, OLDA, but
    Cat. No. 1120
    exclude 2-Arachidonylglycerol and also classical,
    receptor agonists such as HU 210 , CP 55,940 and
    WIN 55,212-2. 2,5,88,92,93
    A number of other non-CB 1 , non-CB 2 pharmacological
    targetsforsomeCB 1 /CB 2 receptoragonistshavebeen
    AM 630 is a CB 2 receptor antagonist (K i = 31.2 nM) that is
    proposed, including several that appear to respond to
    165-fold selective over CB 1 . The ligand displays inverse
    agonist concentrations of 1 micromolar or less (Table
    agonist properties in CHO cells expressing CB 2 receptors
    3), and hence to possess sensitivity to these ligands
    and behaves as a weak partial/inverse agonist at CB 1
    of the same order as that exhibited by CB 1 or CB 2
    receptors. Thus, for example, anandamide interacts
    Hosohata et al (1997) AM630 is a competitive cannabinoid receptor antagonist
    at submicromolar concentrations with several types
    in the guinea pig brain. Life Sci. 61 PL115. Hosohata et al (1997) AM630
    antagonism of cannabinoid-stimulated [ 35 S]GTP γ S binding in the mouse brain.
    of ligand-gated and voltage-gated ion channels,
    Eur.J.Pharmacol. 321 R1. Landsman et al (1998) AM630 is an inverse agonist
    some (but not all) of which are also sensitive
    at the human cannabinoid CB 1 receptor. Life Sci. 62 PL109. Ross et al (1999)
    Agonist-inverse agonist characterization at CB 1 and CB 2 cannabinoid receptors
    9 -THC,
    of L759633, L759656 and AM630. Br.J.Pharmacol. 126 665.
    WIN 55,212-2 and/or JWH 015 (Table 3). There is
    (Sold with the permission of the University of Connecticut)
    evidence too that 9 -THC also interacts potently with
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