The effect of neuroleptic drugs on DPPC/sphingomyelin/cholesterol membranes. (July 2020)

• Record Type: Journal Article
• Authors: Pérez-Isidoro, R.; Costas, M.
• Is Part Of: Chemistry and physics of lipids. Volume 229(2020)
• Publication Date: 2020-07
• Subjects: DSC differential scanning calorimetry -- MLV multilamellar vesicles -- LUV large unilamellar vesicles -- Tm phase transition temperature -- Cp heat capacity -- DPPC 1, 2-dipalmitoyl-sn-glycero-3-phosphocholine -- SM N-octadecanoyl-d-erythro-sphingosylphosphorylcholine (sphingomyelin brain porcine) -- CHO cholesterol -- TFP trifluoperazine -- CZP clozapine -- HPD haloperidol decanoate -- QTP quetiapine hemifumarate -- OLP olanzapine -- ARP aripiprazole -- AMS amisulpride; Neuroleptic drugs -- Neuropsychiatric disorders -- Calorimetry -- Lipid membrane -- Lipid bilayers -- Gel-fluid phase transition; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipids; Periodicals; Electronic journals; 547.77
• DOI: 10.1016/j.chemphyslip.2020.104913
• Languages: English
• ISSNs: 0009-3084

Abstract

Graphical abstract: Highlights: Neuroleptics fluidize and disorder the lipid bilayers composed of DPPC, sphingomyelin, and cholesterol. Drug protonated species produce stronger effects on the lipid bilayer. The driving force for neuroleptics insertion into the bilayer is entropic in nature. High drug concentrations revert fluidization or abolishes bilayer thermal transition. Some neuroleptics induce the formation of drug rich domains in the lipid bilayer. Neuroleptic-protein receptor binding occur in a fluidized and disordered membrane. Abstract: The hydrophobic nature of neuroleptic drugs renders that these molecules interact not only with protein receptors, but also with the lipids constituting the membrane bilayer. We present a systematic study of the effect of seven neuroleptic drugs on a biomembrane model composed of DPPC, sphingomyelin, and cholesterol. Differential scanning calorimetry (DSC) measurements were used to monitor the gel-fluid phase transition of the lipid bilayer at three pH values and also as a function of drug concentration. The implementation of a new methodology to mix lipids homogeneously allowed us to assemble bilayers completely free of organic solvents. The seven neuroleptics were: trifluoperazine, haloperidol decanoate, clozapine, quetiapine, olanzapine, aripiprazole, and amisulpride. The DSC results show that the insertion of the drug into the bilayer produces a fluidization and a disordering of the bilayer. The bilayer perturbation is qualitatively the same for all the studied drugs, but quantitatively different. The driving force for the neuroleptic drug to place itself in the lipid bilayer is entropic in nature, signaling to the importance of the size and geometry of the drugs. The drug protonated species produce stronger effects than their non-protonated forms. At high concentrations two of the neuroleptics revert the fluidization effect and another completely abolishes the gel-fluid transition. The DSC data and the associated discussion contribute to the understanding of the interactions between neuroleptic drugs and lipid membranes.