Investigation of the interaction of environmental chemicals with Cannabinoid-1 (CB1) receptors in mammalian brain using the [3H]CP-55,940 binding assay

Cannabinoid-1 (CB1) receptors are G protein-coupled receptors, which are widely distributed in mammalian brain. This investigation primarily examines several voltage-gated sodium channel targeting compounds for their ability to interfere with the binding of the CB1 receptor specific agonist [3H]CP-55,940 to the CB1 receptors in a membrane fraction prepared from mouse brain. The study found that the pyrethroid insecticide [1RS]trans-permethrin is more potent at displacing radioligand (IC50 7.1 µM) than its cis counterpart [1RS]cis-permethrin (IC50 18.1 µM). Two other pyrethroids, deltamethrin and cypermethrin exhibited intermediate potency (IC50s 9.3 and 11.2 µM, respectively). The dihydropyrazole insecticide RH3421 was the most potent within the group of insecticides tested with an IC50 value of 5.7 µM. Another dihydropyrazole, RH5529 was less potent (IC50 16.5 µM). Other pesticides and drugs were inactive or barely active. The toxicological relevance of these findings remains to be clarified in future experiments.