NONCLASSICAL AND ENDOGENOUS CANNABINOIDS - EFFECTS ON THE ORDERING OFBRAIN MEMBRANES

The effects of several nonclassical cannabinoids and the endogenous ca nnabinoid ligand, anandamide on the lipid ordering of rat brain synapt ic plasma membranes (SPM) were examined and compared to Delta(9)-tetra hydrocannabinol (Delta(9)-THC). SPM order was determined using fluores cence polarization. All compounds tested affected membrane ordering. D elta(9)-THC, CP-55,940, CP-55,244 and WIN-55212 decreased lipid orderi ng in SPM. Some stereospecificity was observed with Delta(9)-THC and W IN-55212, but not other compounds. Anandamide also decreased lipid ord er as did its putative precursor, arachidonic acid. In contrast to the se compounds, levonantradol increased SPM lipid order. Although all ph armacologically active cannabinoids affect SPM lipid order, potency on this measure does not correlate well with their pharmacological poten cy. The results of this study suggest that membrane perturbation (eith er increases or decreases in lipid order) may be a necessary character istic for cannabinoid pharmacological activity, but it is not a primar y or sufficient determinate of action for this class of drugs.