www.tocris.com
Cannabinoid
Receptor Ligands
Roger G Pertwee
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen
AB25 2ZD, Scotland, UK. Phone: + 44 (0)1224 555740, Fax: + 44 (0)1224 555844, E-mail: rgp@abdn.ac.uk
Roger Pertwee is currently Professor of Neuropharmacology at the University of Aberdeen and Director of
Pharmacology for GW Pharmaceuticals. His research focuses on the pharmacology of cannabis and its constituents
and of cannabinoid receptors and cannabis-derived, synthetic and endogenous ligands for these receptors.
The Endocannabinoid System
including immune cells. CB 2 receptors are located
Two types of cannabinoid receptor have so far been
predominantly in immune cells both within and
identified. 1,2 These are the CB 1 receptor, cloned
outside the central nervous system, the functions
in 1990, 3 and the CB 2 receptor, cloned in 1993, 4
of these receptors including modulation of cytokine
both of which are members of the superfamily of
release and of immune cell migration. In the brain,
G-protein-coupled receptors. The cloning of these
CB 2 receptors are expressed by microglia, 7 by blood
receptors prompted the development of mice from
vessels, 7 and by some neurons. 8,9 However, the role
which cannabinoid CB 1 and/or CB 2 receptors have
of neuronal CB 2 receptors is currently unknown.
been genetically deleted and these transgenic
The central distribution pattern of CB 1 receptors is
animals, particularly CB 1 knockout mice, are now
heterogeneous and accounts for several prominent
widely used to explore the physiological and
pharmacological properties of CB 1 receptor agonists,
pathological functions of cannabinoid receptors. 1,5,6
for example their ability to impair cognition and
CB 1 receptors are found mainly at the terminals of
memory and to alter the control of motor function.Thus
central and peripheral neurons where they usually
the cerebral cortex, hippocampus, lateral caudate-
mediate inhibition of neurotransmitter release.
putamen, substantia nigra pars reticulata, globus
They are also present in some non-neuronal cells,
pallidus, entopeduncular nucleus and the molecular
Figure 1 | Structures of the plant cannabinoids, 9 -tetrahydrocannabinol ( 9 -THC),
8 -tetrahydrocannabinol ( 8 -THC), the synthetic cannabinoids HU 210, CP 55,940 , WIN 55,212-2 and
WIN 55,212-3, and the endogenous cannabinoids anandamide and 2-arachidonylglycerol (see also
Table 1)
O
O
11
9
N
N
8
10
OH
O
O
H
OH
7
10b
1
H
2
N
N
H
10a
3
13
H
6
O 5
12
4
1'
3'
5'
O
O
O
9 -THC
8 -THC
OH
HO
OH
OH
O
H
OH
8
5
3
1'
OH
O
N
H
OH
10
H
2'
O
O
20
OH
17
19
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