title: Interaction of injectable neurotropic drugs with the red cell membrane.
abstract: The normal red blood cell (RBC) shape is a biconcave discocyte. An intercalation of a drug in the outer half of the membrane lipid bilayer leads to echinocytosis, an intercalation in the inner half to stomatocytosis. We have used the shape transforming capacity of RBCs as a model to analyse the membrane interaction potential of various neurotropic drugs. Chlorpromazine, clomipramine, citalopram, clonazepam, and diazepam induced a reversible stomatocytosis, phenytoin induced echinocytosis, while the anticonvulsants levetiracetam, valproic acid and phenobarbital had no effect. This diversity of RBC shape transformations suggests that the pharmacological action is not linked to the membrane interaction. We conclude that this simple RBC shape transformation assay could be a useful tool to screen for potential drug interactions with cell membranes.
authors.affiliation: Department of Internal Medicine, Kantonsspital Graubünden, Chur, Switzerland. Electronic address: walter.reinhart@ksgr.ch.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Reinhart
authors.affiliation: Department of Internal Medicine, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Szabina
authors.initials: S
authors.lastname: Lubszky
authors.affiliation: AO Research Institute, Davos, Switzerland.
authors.forename: Sandra
authors.initials: S
authors.lastname: Thöny
authors.affiliation: Division of Transfusion Medicine, Kantonsspital Graubünden, Chur, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schulzki
mesh_terms: D002491:Central Nervous System Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology; D015283:Citalopram / Q000494:pharmacology; D002997:Clomipramine / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007267:Injections; D000077287:Levetiracetam; D008855:Microscopy, Electron, Scanning; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010634:Phenobarbital / Q000494:pharmacology; D010672:Phenytoin / Q000494:pharmacology; D010889:Piracetam / Q000031:analogs & derivatives / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
chemical_list: D002491:Central Nervous System Agents; D018377:Neurotransmitter Agents; D015283:Citalopram; D000077287:Levetiracetam; D002998:Clonazepam; D014635:Valproic Acid; D010672:Phenytoin; D002997:Clomipramine; D003975:Diazepam; D002746:Chlorpromazine; D010634:Phenobarbital; D010889:Piracetam
keywords: Drugs; Echinocyte; Erythrocyte; Membrane; Stomatocyte