Cannabinoid Receptor Ligands
K + and L-type Ca 2+ channels, CYP enzymes,
Figure 9 | Structures of (–)-cannabidiol (CBD),
acyltransferase, a neuronal non-CB 1 site of action
(–)- ∆ 9 -tetrahydrocannabivarin ( ∆ 9 -THCV), O-1602,
in the mouse vas deferens, and the putative
abnormal-cannabidiol (abn-CBD) and O-1918
non-CB 1 , non-CB 2 , non-TRPV1 “abnormal-CBD
receptor” that has been postulated to be present
7
in tissues such as mesenteric arteries and in
1
6
2
OH
microglial cells; 2,88,123
OH
3'
H
5
2'
4'
4
3
H
5'
significant affinity for the CB 1 receptor and behave
9
8
OH
6'
1''
3''
5''
O
as agonists (abnormal-CBD and O-1602) or
antagonists (O-1918) for the putative abnormal-
∆ 9 -THCV
CBD receptor; 2,88,96
OMe
serine (Figure 10), which may be an endogenous
agonist for the abnormal-CBD receptor as it
OH
appears to activate this putative receptor when
OH
OH
OMe
OH
added exogenously (EC 50 = 550 or ca 1200 nM),
and which binds only weakly to CB 1 receptors
O-1602
(K i > 10 µ M) and does not bind to CB 2 or TRPV1
receptors at concentrations of up to 30 µ M; 124
(Bold Link Text Denotes Compounds Available From Tocris)
anandamide/capsaicin
structural
hybrid,
N -vanillyl arachidonyl amide (arvanil ; Figure 10),
compounds so far found to inhibit the cellular uptake
which binds to TRPV1 receptors at concentrations
of anandamide do so by targeting an anandamide
in the low nanomolar range, binds to CB 1 receptors
transport protein or by attenuating FAAH-mediated
and inhibits the cellular uptake of anandamide at
metabolism of anandamide to cause an intracellular
concentrations in the low micromolar range and
accumulation of this fatty acid amide that is sufficient
may also have one or more as yet unidentified
to oppose its entry into the cell by diffusion. 25-27
non-CB 1 , non-TRPV1 sites of action; 125,126
Some Other Notable Ligands
In addition to the CB 1 and CB 2 receptor ligands
Org 29647
and
Org
27759
(Figure
11),
already discussed there are a number of other
experiments with which have revealed the
compounds that deserve mention either because
presence of an allosteric site on the cannabinoid
they can modulate some effects of established
CB 1 receptor that constitutes a new target through
CB 1 /CB 2 receptor agonists through seemingly novel
which CB 1 receptor activation by endogenously
mechanisms or because they share the apparent
released endocannabinoids could be modulated,
ability of such agonists to target certain putative non-
for example to combat inflammatory pain, obesity
CB 1 , non-CB 2 receptors. These compounds are:
or nicotine dependence. 127
(Figure 9), which displaces [ 3 H]CP 55,940 from
Figure 10 | Structures of arvanil and
CB 1 and CB 2 receptors at concentrations in
N -arachidonoyl- L -serine
the low nanomolar range (K i = 75.4 and 62.8
nM respectively) and behaves as a CB 1 and
CB 2 receptor competitive antagonist, exhibiting
O
greater potency against CP 55,940 in the mouse
OMe
N
isolated vas deferens and in membranes obtained
H
OH
from human CB 2 -transfected cells (apparent K B =
10 nM) than in mouse brain membranes (apparent
K B = 93 nM); 121
non-psychoactive
plant
cannabinoid,
OH
O
(–)-Cannabidiol (CBD; Figure 9), which lacks
N
CO 2 H
significant affinity for CB 1 or CB 2 receptors, has
H
therapeutic potential (e.g. as an anti-inflammatory
agent), possesses anti-oxidant/neuroprotective
properties and, at sub-micromolar concentrations,
N -Arachidonoyl- L -serine
activates blocks or inhibits a number of established
or putative pharmacological targets that include an
adenosine transporter 122 and also delayed rectifier
(Bold Link Text Denotes Compounds Available From Tocris)
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