pH-dependent effects of chlorpromazine on liposomes and erythrocyte membranes.
Chlorpromazine (CPZ) is an amphipathic antipsychotic drug that binds to erythrocytes reaching in this way the central nervous system. CPZ is a basic molecule with pK=8.6. This paper reports on CPZ-induced lysis of red blood cells and liposomes. Haemolysis was tested under hypotonic conditions, in the pH range 5.0-10.0. Cell sensitivity towards CPZ increased with increasing pH. Increasing pH caused also a decrease in the critical micellar concentrations of CPZ. These results are interpreted in terms of a competition between repulsive electrostatic forces and attractive hydrophobic forces, that would act both in pure CPZ and in mixed CPZ-phospholipid micelles. In order to eliminate possible pH effects mediated by red blood cell proteins, experiments were carried out in which CPZ induced release of a fluorescent dye from liposomes (large unilamellar vesicles). The latter observations confirmed that membrane sensitivity towards CPZ was increased at higher pH.
Ahyayauch
Hasna
H
Laboratory of Pharmacology, Department of Biology, Faculty of Science, Abdelmalek Essaâdi University, Tetouan, Morocco. hasna@mixmail.com
Goñi
Félix M
FM
Bennouna
Mohammed
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002746:Chlorpromazine / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D007038:Hypotonic Solutions; D008081:Liposomes; D051381:Rats; D012965:Sodium Chloride
D014150:Antipsychotic Agents; D007038:Hypotonic Solutions; D008081:Liposomes; D012965:Sodium Chloride; D002746:Chlorpromazine