Functional bioassays selection

The best CB2-selective agonists to have been developed to date are all non-eicosanoid cannabinoids (Howlett et al. 2002 Ibrahim et al. 2003 Pertwee 1999a). They include the classical cannabinoids, L-759633, L-759656 and JWH-133, the non-classical cannabinoid HU-308, and the aminoalkylindole AM1241 (Figs. 5,6 and 7). All these ligands bind more readily to CB2 than to CBi receptors (Table 2) and have also been shown to behave as potent CB2-selective agonists in functional bioassays (Hanus et al. 1999 Ibrahim et al. 2003 Pertwee 2000 Ross et al. 1999a). 

Most commonly, bioassays for the evaluation of the acute toxic effects of pesticides are based on single aquatic species selected to be representative of a range of taxonomic and functional groups, i.e., bacteria, algae, invertebrates or fish [ 53,54]. Generally, toxicity evaluation using a single species is the alternative of choice rather than the use of multiple species, because extrapolation of effects to an ecosystem is more difficult and can often lead to incorrect conclusions. 

Possibly, the most extensive screening of NPs ever undertaken was conducted by the US National Cancer Institute, starting In i960. Over two decades, 114,000 extracts from 35,000 plant samples (from over 12,000 species) were screened but less than 1% showed selective anticancer potential. One assumes each sample must have contained tens or hundreds of NPs so the hit rate was really much lower. However, the bioassays used have a very questionable relationship to any functional significance of endogenous NPs because plants do not form cancers in the manner that animals do (see Chapter 8). 

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