title: Pathways involved in trifluoperazine-, dibucaine- and praziquantel-induced hemolysis.
abstract: This work elucidates differences in the hemolytic pathway developed by the antipsychotic trifluoperazine (TFP), the local anesthetic dibucaine (DBC) and the antihelminthic praziquantel (PZQ). Their partition coefficients (P) were measured at pH 7.4 between n-octanol, microsomes, liposomes, erythrocyte ghosts and n-octanol/water. The effective drug:lipid molar ratios for the onset of membrane solubilization (ReSAT) and complete hemolysis (ReSOL) were calculated from the experimental P values and compared with a classical surface-active compound treatment Lichtenberg, D. Biochim. Biophys. Acta 821 (1985) 470-478[. The contribution of charged/uncharged forms of TFP and DBC for the hemolytic activity was also analyzed. In all cases the hemolytic phenomena could be related to the monomeric drug insertion into the membrane. Only for TFP at isosmotic condition lysis occurs at concentrations beyond the CMC of the drug, indicating that micellization facilitates TFP hemolytic effect, while DBC and PZQ reach a real membrane saturation at their monomeric form.
authors.affiliation: Department of Biochemistry, State University of Campinas (Unicamp), SP, Brazil.
authors.forename: S V
authors.initials: SV
authors.lastname: Malheiros
authors.forename: N C
authors.initials: NC
authors.lastname: Meirelles
authors.forename: E
authors.initials: E
authors.lastname: de Paula
mesh_terms: D000779:Anesthetics, Local / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000737:chemistry / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000737:chemistry / Q000494:pharmacology; D003992:Dibucaine / Q000737:chemistry / Q000494:pharmacology*; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects* / Q000502:physiology; D006461:Hemolysis; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008051:Lipid Bilayers; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects* / Q000502:physiology; D011223:Praziquantel / Q000737:chemistry / Q000494:pharmacology*; D014268:Trifluoperazine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000779:Anesthetics, Local; D000871:Anthelmintics; D014150:Antipsychotic Agents; D008051:Lipid Bilayers; D014268:Trifluoperazine; D011223:Praziquantel; D003992:Dibucaine