title: Interactions between tricyclic antidepressants and phospholipid bilayer membranes.
abstract: Participation of electrostatic and other noncovalent interactions in the binding of tricyclic antidepressants (TCAs) to the lipid bilayers was estimated from pH-dependencies of imipramine, desipramine, amitriptyline and nortriptyline binding to the lipid bilayers prepared from different phospholipids, both electroneutral and acidic. The binding was studied using a radioligand binding assay. It was found that the membrane phospholipid composition and methylation of the acyl side chain of TCA has a decisive effect on participation of particular noncovalent interactions in the binding. Apparent high-affinity binding of TCAs to the phosphatidylcholine or phosphatidylethanolamine membranes are achieved mainly by incorporation of uncharged drug molecules into the hydrophobic core of the bilayers. Van der Waals forces and hydrophobic effect are responsible for this binding. Both charged and uncharged drug molecules bind to phosphatidylserine membranes, therefore coulomb- or ion-induced dipole interactions play a role in these binding. Different spatial distribution of charged residues within the interface causes different electrostatic interactions between charged TCAs and vesicles formed from phosphatidylserine and phosphatidylinositol. The data supports the hypothesis under which TCAs could have effect on affective disorders partially via binding to the lipid part of the membrane and following changes of lipid-protein interactions.
authors.affiliation: Department of Psychiatry, 1st Faculty of Medicine, Charles University, Ke Karlovu 11, 120 00 Prague 2, Czech Republic. zfisar@lf1.cuni.cz
authors.forename: Z
authors.initials: Z
authors.lastname: Fisar
mesh_terms: D000929:Antidepressive Agents, Tricyclic / Q000737:chemistry*; D001665:Binding Sites; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D055672:Static Electricity
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008051:Lipid Bilayers; D008081:Liposomes; D010743:Phospholipids