Molar volume relationships and the specific inhibition of a synaptosomal enzyme by psychoactive cannabinoids.

The ability of a number of lipophilic compounds to inhibit the mouse-brain synaptosomal enzyme acyl coenzyme A:lysophosphatidylcholine acyltransferase has been measured in vitro. Psychoactive cannabinoids inhibit the enzyme at concentrations much lower than is predicted from their capacity to act as lipid-soluble anesthetics. Nonpsychoactive cannabinoids do not show specific inhibition. Molar volume relationships are used to show that, while all lipid-soluble molecules exert some inhibitory effect in proportion to their ability to dissolve in biological membranes, psychoactive cannabinoids have an inhibitory effect greatly in excess of their anesthetic potency. The isoprenoid convulsant thujone has been suggested to have psychoactivity similar to cannabinoids but does not mimic the cannabinoids in inhibiting the synaptosomal enzyme. Molar volumes and specific interactions are used in structure-activity correlations which yield information on the relative concentrations of biophase in drug-responsive systems and the specificity of membrane-active drugs.