Chlorpromazine interaction with phosphatidylserines: A 13C and 31P solid-state NMR study

Gjerde, Anja Underhaug; Holmsen, Holm; Nerdal, Willy

doi:10.1016/j.bbalip.2004.01.004

Cited by 33 publications

(6 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They were all able to induce significant changes in d-spacing, d w and d pp values as evaluated by XRD methods. Results obtained from our studied CPZ sample are in accordance with data published in the ordering effect described with polyunsaturated lipids [10][11][12][13]. Similarly, the observed Lo d pp decrease is in agreement with the CPZ disordering effect seen in DMPC/cholesterol samples [10].…”

Section: Discussionsupporting

confidence: 95%

“…Similarly, the observed Lo d pp decrease is in agreement with the CPZ disordering effect seen in DMPC/cholesterol samples [10]. A molecular understanding of these results suggests that the hydrophobic CPZ tricyclic ring structure partitions with relative ease into the bulk hydrocarbon phase of membrane bilayers, while its polar propylamine tail region which is hydrophilic, interacts with phospholipids polar head groups [12,13]. CPZ is also known to interact with negatively charged glycerophospholipids [3,12,14].…”

Section: Discussionsupporting

confidence: 83%

“…A molecular understanding of these results suggests that the hydrophobic CPZ tricyclic ring structure partitions with relative ease into the bulk hydrocarbon phase of membrane bilayers, while its polar propylamine tail region which is hydrophilic, interacts with phospholipids polar head groups [12,13]. CPZ is also known to interact with negatively charged glycerophospholipids [3,12,14]. Its partition coefficient decreases with phospholipid fatty acid lengths and in presence of cholesterol [10,15].…”

Section: Discussionmentioning

confidence: 90%

See 2 more Smart Citations

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Tessier

Nuss

Staneva

et al. 2008

Journal of Colloid and Interface Science

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 95%

Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Tessier

Nuss

Staneva

et al. 2008

Journal of Colloid and Interface Science

View full text Add to dashboard Cite

“…The greatest area-increasing effect on the DPPS monolayers was with PRZ and CTM, both of which are cationic amphiphiles (Scheme 1 ), and they have the same effect on DPPS monolayers as the phenothiazine drugs chlorpromazine (CPZ) [ 1 ] and trifluoperazine (TFP) [ 9 , 67 ]. Solid-state 13 C- and 31 P-NMR studies of the interaction of CPZ and porcine brain phosphatidyl serine (PBPS) bilayers have clearly shown that the phenothiazine moiety is intercalated between the acyl chains of PBPS, while the cationic tail group is anchored electrostatically by the negatively charged phosphate and carboxyl groups [ 73 ]. Promethazine is also a phenothiazine derivative (Scheme 1 ) and is, like CTM, most likely intercalated in the DPPS monolayer in the same way as CPZ.…”

Section: Discussionmentioning

confidence: 99%

In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

et al. 2009

Self Cite

View full text Add to dashboard Cite

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs' intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A 2 (PLA 2 ) and polyphosphoinositide (PPI) metabolism in thrombinstimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA 2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA 2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects.

show abstract

“…Also, chlorpromazine has been shown to have considerable affinity to the POPC and POPC/POPS liposomes . The interaction depends on the charge of a lipid polar group; chlorpromazine binds more strongly to acidic lipids than to neutral ones . Once in the membrane, chlorpromazine acts as factor affecting membrane permeability and fluidity .…”

Section: Introductionmentioning

confidence: 99%

Sulpiride, Amisulpride, Thioridazine, and Olanzapine: Interaction with Model Membranes. Thermodynamic and Structural Aspects

Skrobecki

Chmielińska

Bonarek

et al. 2017

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Neuroleptic drugs are widely applied in effective treatment of schizophrenia and related disorders. The lipophilic character of neuroleptics means that they tend to accumulate in the lipid membranes, impacting their functioning and processing. In this paper, the effect of four drugs, namely, thioridazine, olanzapine, sulpiride, and amisulpride, on neutral and negatively charged lipid bilayers was examined. The interaction of neuroleptics with lipids and the subsequent changes in the membrane physical properties was assessed using several complementary biophysical approaches (isothermal titration calorimetry, electron paramagnetic resonance spectroscopy, dynamic light scattering, and ζ potential measurements). We have determined the thermodynamic parameters, that is, the enthalpy of interaction and the binding constant, to describe the interactions of the investigated drugs with model membranes. Unlike thioridazine and olanzapine, which bind to both neutral and negatively charged membranes, amisulpride interacts with only the negatively charged one, while sulpiride does not bind to any of them. The mechanism of olanzapine and thioridazine insertion into the bilayer membrane cannot be described merely by a simple molecule partition between two different phases (the aqueous and the lipid phase). We have estimated the number of protons transferred in the course of drug binding to determine which of its forms, ionized or neutral, binds more strongly to the membrane. Finally, electron paramagnetic resonance results indicated that the drugs are localized near the water-membrane interface of the bilayer and presence of a negative charge promotes their burying deeper into the membrane.

show abstract

Chlorpromazine interaction with phosphatidylserines: A 13C and 31P solid-state NMR study

Cited by 33 publications

References 41 publications

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

Modification of membrane heterogeneity by antipsychotic drugs: An X-ray diffraction comparative study

In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

Sulpiride, Amisulpride, Thioridazine, and Olanzapine: Interaction with Model Membranes. Thermodynamic and Structural Aspects

Contact Info

Product

Resources

About