title: In vitro effects of the anti-Alzheimer drug memantine on the human erythrocyte membrane and molecular models.
abstract: Memantine is a NMDA antagonist receptor clinically used for treating Alzheimer's disease. NMDA receptors are present in the human neurons and erythrocyte membranes. The aim of the present study was to investigate the effects of memantine on human erythrocytes. With this purpose, the drug was developed to in vitro interact with human red cells and bilayers built-up of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE). The latter represent lipids respectively present in both outer and inner monolayers of the red cell membrane. Results obtained by scanning electron microscopy (SEM) showed that memantine changed the normal biconcave shape of red cells to cup-shaped stomatocytes. According to the bilayer-couple hypothesis the drug intercalated into the inner monolayer of the erythrocyte membrane. Experimental results obtained by X-ray diffraction on multibilayers of DMPC and DMPE, and by differential scanning calorimetry on multilamellar vesicles indicated that memantine preferentially interacted with DMPC in a concentration-dependent manner. Thus, it can be concluded that in the low therapeutic plasma concentration of circa 1 μM memantine is located in NMDA receptor channel without affecting the erythrocyte shape. However, at higher concentrations, once the receptors became saturated excess of memantine molecules (20 μM) would interact with phosphoinositide lipids present in the inner monolayer of the erythrocyte membrane inducing the formation of stomatocytes. However, 40-50 μM memantine was required to interact with isolated phosphatidylcholine bilayers.
authors.affiliation: Faculty of Chemical Sciences, University of Concepción, Concepción, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Zambrano
authors.affiliation: Faculty of Chemical Sciences, University of Concepción, Concepción, Chile. Electronic address: msuwalsk@udec.cl.
authors.forename: Mario
authors.initials: M
authors.lastname: Suwalsky
authors.affiliation: Faculty of Biological Sciences, University of Concepción, Concepción, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Villena
authors.affiliation: Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland; Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Jemiola-Rzeminska
authors.affiliation: Malopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland; Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Strzalka
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D002152:Calorimetry, Differential Scanning; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004910:Erythrocyte Membrane / Q000737:chemistry / Q000187:drug effects*; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008559:Memantine / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D008968:Molecular Conformation; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D013816:Thermodynamics; D014961:X-Ray Diffraction
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D004134:Dimyristoylphosphatidylcholine; D008559:Memantine; C018525:1,2-dimyristoylphosphatidylethanolamine
keywords: Cell membrane; Human erythrocyte; Memantine; Phospholipid bilayer