Cannabinoids

Pharmacological Actions of Cannabinoids 9

Table 2.(continued)

Agonist CB 1 CB 2 Reference

Kivalue (nM) Kivalue (nM)

1.89 0.28 Showalter et al. 1996

62.3 3.3 Felder et al. 1995

123 4.1 Shire et al. 1996

9.87 0.29 Iwamura et al. 2001

CB 2 -selective agonists in order of increasing CB 2 /CB 1 selectivity

AM1241 280 b 3.4c Ibrahim et al. 2003

3-(1′ 1 ′-dimethylbutyl)-1- 677 b 3.4 Huffman et al. 1999

deoxy-∆^8 -THC (JWH-133)

L-759633 1,043 6.4 Ross et al. 1999a

15,850 20 Gareau et al. 1996

L-759656 529 b 35 Huffman et al. 1999

713 b 57 Huffman et al. 2002

4,888 11.8 Ross et al. 1999a

>20,000 19.4 Gareau et al. 1996

HU-308 >10,000e,b 22.7e,d Hanus et al. 1999

See Figs. 1 to 9 for the structures of the compounds listed in this table.
DMH, dimethylheptyl; ND, not determined; THC, tetrahydrocannabinol.
aWith phenylmethylsulphonyl fluoride (PMSF) in order to inhibit enzymic hydrolysis.
bBinding to rat cannabinoid receptors on transfected cells or on brain (CB 1 ) or spleen tissue (CB 2 ).
cBinding to mouse brain (CB 1 ) or spleen tissue (CB 2 ).
dSpecies unspecified. All other data from experiments with human cannabinoid receptors.

eDisplacement of [ (^3) H]HU243 from CB 1 -andCB 2 -specific binding sites.
fDisplacement of [ (^3) H]BAY-38-7271 from CB 1 -andCB 2 -specific binding sites.
tors to which at least some CB 1 and/or CB 2 receptor ligands can bind (Sect. 4).
Radiolabelled probes for single photon emission computed tomography (SPECT)
or positron emission tomography (PET) have also been developed (reviewed in
Gifford et al. 2002; see also the chapter by Lindsey et al., this volume).

2.

In Vitro Functional Bioassays

2.2.

Assays Using Whole Cells or Cell Membranes

The most commonly employed assays using whole cells or cell membranes are

the [^35 S]guanosine-5′-O-(3-thiotriphosphate) ([^35 S]GTPγS) binding assay and the

cyclic AMP assay. The first measures cannabinoid receptor agonist-stimulated

binding to G proteins of the hydrolysis-resistant GTP analogue, [^35 S]GTPγS,

whereas the cyclic AMP assay relies on cannabinoid receptor-mediated inhibition
(usual effect) or enhancement of basal or drug-induced cyclic AMP production