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

Publisher Website
Google Scholar
Abstract
The ability of a number of lipophilic compounds to inhibit the mouse-brain synaptosomal enzyme acyl coenzyme A:lysophosphatidylcholine acyltransferase was measured in-vitro. Psychoactive cannabinoids [.delta.-9-tetrahydrocannabinol] inhibited the enzyme at concentrations much lower than predicted from their capacity to act as lipid-soluble anesthetics. Nonpsychoactive cannabinoids did not show specific inhibition. Molar volume relationships showed that, while all lipid-soluble molecules exerted some inhibitory effect in proportion to their ability to dissolve in biological membranes, psychoactive cannabinoids had an inhibitory effect greatly in excess of their anesthetic potency. The isoprenoid convulsant thujone was suggested to have psychoactivity similar to cannabinoids but did not mimic the cannabinoids in inhibiting the synaptosomal enzyme. Molar volumes and specific interactions were used in structure-activity correlations which yielded information on the relative concentrations of biophase in drug-responsive systems and the specificity of membrane-active drugs.
Keywords