Interactions of the antiviral and antiparkinson agent amantadine with lipid membranes and human erythrocytes

Aimed to better understand the molecular mechanisms of its interactions with cell membranes, human erythrocyte and molecular models of the red cell membrane were utilized. The latter consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of amantadine to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction, fluorescence spectroscopy and differential scanning calorimetry (DSC). In an attempt to further elucidate its effects on cell membranes, the present work also examined amantadine influence on the morphology of intact human erythrocytes by means of scanning electron microscopy (SEM). Results indicated that amantadine induced morphological changes to human erythrocytes and interacted in a concentration-dependent manner with DMPC bilayers in contrast to DMPE that was hardly affected by the presence of the drug. [Display omitted] •Interactions of amantadine with human erythrocytes and lipid bilayers were assessed.•Amantadine changed the morphology of erythrocytes inducing formation of echinocytes.•This change of shape indicates that it was inserted in the outer leaflet of the erythrocyte membrane.•Amantadine interacted with a class of phospholipid present in the outer leaflet of the erythrocyte membrane.