Interaction of psychedelic tryptamine derivatives with a lipid bilayer
Chemistry and Physics of Lipids January 7, 2023 Fateme Zohairi, Himanshu Khandelia, Ali Asghar Hakami Zanjani 20 citations
Naturally occurring psychedelics have therapeutic potential for anxiety, depression, migraine, and addiction. Their effects may arise from binding to serotonin receptors or by altering neuronal membrane properties. Using all-atom MD simulations, three tryptamine compounds (dimethyltryptamine, bufotenine, and 5-MeO-DMT) in neutral and charged forms were studied in a model bilayer membrane. All compounds partition into the bilayer and change membrane properties to different extents. Neutral tryptamines partition almost completely; dimethyltryptamine and 5-MeO-DMT cross the membrane spontaneously, but bufotenine does not, despite having the greatest effect on membrane structure. Protonated compounds only partially partition and cannot cross the membrane. Subtle chemical structure changes significantly influence partitioning and membrane passage.