Hydrophobicity of Tricyclic and Policyclic Antidepressants Influences, their Interaction with Lipid Bilayers

摘要

Many theoretical and experimental studies are dedicated to the interaction of drugs with lipid bilayers. The hydrophobic properties of tricyclic antidepressants (amitriptyline and imipramine) and policyclic antidepressants (hypericin) were evaluated by two methods: black lipid membranes (BLM) and molecular dynamics. BLM studies indicate a deeper insertion into the lipid bilayers of the hypericin (5 μM) than of the tricyclic antidepressants (10-50 μM). Experimental data are well correlated with theoretical data (obtained with HYPERCHEM 6) that indicate a high hydrophobicity of the hypericin molecule (log P = 7.98) and very low coefficients for amitriptyline (log P = 2.36) and imipramine (log P = 0.23), where P represents the octanol-water partition coefficient. Thus, mathematical evaluations of drug properties correlated with experimental data could represent the future of the pharmaceutical industry.