Interaction of injectable neurotropic drugs with the red cell membrane

Toxicol In Vitro. 2014 Oct;28(7):1274-9. doi: 10.1016/j.tiv.2014.06.008. Epub 2014 Jul 2.

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.

Keywords: Drugs; Echinocyte; Erythrocyte; Membrane; Stomatocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Central Nervous System Agents / pharmacology*
  • Chlorpromazine / pharmacology
  • Citalopram / pharmacology
  • Clomipramine / pharmacology
  • Clonazepam / pharmacology
  • Diazepam / pharmacology
  • Erythrocytes / cytology
  • Erythrocytes / drug effects*
  • Erythrocytes / metabolism
  • Erythrocytes / ultrastructure
  • Humans
  • Injections
  • Levetiracetam
  • Microscopy, Electron, Scanning
  • Neurotransmitter Agents / pharmacology*
  • Phenobarbital / pharmacology
  • Phenytoin / pharmacology
  • Piracetam / analogs & derivatives
  • Piracetam / pharmacology
  • Valproic Acid / pharmacology

Substances

  • Central Nervous System Agents
  • Neurotransmitter Agents
  • Citalopram
  • Levetiracetam
  • Clonazepam
  • Valproic Acid
  • Phenytoin
  • Clomipramine
  • Diazepam
  • Chlorpromazine
  • Phenobarbital
  • Piracetam