Differential binding of chlorpromazine to human blood cells: Application of the hygroscopic desorption method

Bondy, Brigitta; Remien, Jörg

doi:10.1016/0024-3205(81)90091-6

Cited by 26 publications

(15 citation statements)

References 13 publications

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“…Our results argue against a large internal pressure existing in ghosts which prevents intercalation of the amphipathic spin probe. Further, these findings support those of Bondy and Remien [4] and Pjura et al [30] who found no significant differences between the partitioning of small molecule amphipaths into liposomes and biological membranes using the technique of hygroscopic desorption. Pjura et al [30] suggested that the divergent results obtained by Conrad and Singer [7,8] might lie in their use of much higher concentrations of amphipaths (e.g., 60/~M chlorpromazine) which could produce membrane damage.…”

Section: Discussionsupporting

confidence: 82%

“…Support for this interpretation comes from the similar probe-probe interaction effects noted for I(12,3)-labeled human erythrocyte ghosts [l l, [17][18][19] and liposomes prepared from erythrocyte ghosts (Figs. [4][5][6]. Clustering of the I(m,n) class of spin probes in lipid sites is not unexpected, as surface balance experiments showed I(5,10) clustering in mixed lipid monolayers [6] and electrophoretic mobility studies indicated I (12,3) clustering in model liposomes below the phase transition [23].…”

Section: Discussionmentioning

confidence: 91%

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Fatty-acid spin probe interactions with erythrocyte ghosts and liposomes prepared from erythrocyte ghosts

1989

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A model for the binding of 5-nitroxide stearate, I(12.3), to human erythrocyte ghosts was developed by comparing spin probe interactions with ghosts and liposomes prepared from ghosts. At low probe/lipid (P/L less than 1/2500), I(12.3) binds to a similar class of high-affinity, noninteracting sites in both ghosts and liposomes, indicating that lipid moieties are responsible for probe uptake. Saturation occurs in both systems with increasing P/L, and, at higher loading (e.g., P/L = 1/360 for ghosts and liposomes), the probe inserts itself at initially dilute sites to form a class of low-affinity sites consisting of clusters of variable size. At still higher P/L ranges (greater than 1/100), much increased probe uptake was observed in ghosts than in liposomes, which was attributed to another class of low-affinity sites, representing nonspecific interactions of I(12.3) with membrane proteins. The nature of the spectral components and ultrafiltration experiments with ghosts labeled at high P/L indicate that both 'dilute' and 'clustered' I(12.3) are due to membrane-incorporated probe.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 91%

Fatty-acid spin probe interactions with erythrocyte ghosts and liposomes prepared from erythrocyte ghosts

1989

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“…It has been recognized that the secondderivative spectrophotometry can eliminate the effect of background signals 12,13) and be usefully applicable to the determination of the partition coefficients of drugs between lipid vesicle and water 10) without the troublesome separation procedures which may disturb the equilibrium states and may cause fluctuation in the temperature of sample solutions. [14][15][16] The use of SUV as a biomembrane model in the thermodynamic studies is considered to be more suitable than multilamellar liposomes that have been widely used where separation procedures were employed.…”

mentioning

confidence: 99%

Thermodynamics of Partitioning of Phenothiazine Drugs between Phosphatidylcholine Bilayer Vesicles and Water Studied by Second-Derivative Spectrophotometry

Takegami

Kitamura

Kitade

et al. 2003

CHEMICAL & PHARMACEUTICAL BULLETIN

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The partition coefficients (Kps) of phenothiazine drugs (trifluoperazine, triflupromazine, chlorpromazine and promazine) between phosphatidylcholine (PC) small unilamellar vesicles (SUV) and water were determined over the temperature range of 10-40 degrees C by a second-derivative spectrophotometric method. The second derivative spectra of each drug solution containing various amounts of SUV showed distinct derivative isosbestic points confirming the entire elimination of the residual background signal effects of the SUV. The Kp values were calculated from the derivative intensity change of the drugs induced by the addition of SUV to the drug buffer solutions (pH 7.4) and obtained with the R.S.D. below 10% (n=3). The van't Hoff analysis of the temperature dependence of Kp values revealed negative deltaH(w-->l) and positive deltaS(w-->l), suggesting an enthalpy/entropy driven mechanism for the phenothiazine partitioning. The negative deltaH(w-->l) implies that the electrostatic interaction, positively charged alkyl amino groups of phenothiazine drugs with negatively charged phosphate groups on the surface of PC SUV, partly contributes to the partitioning. The existence of halogen atom(s) on the phenothiazine ring at position C-2 enhanced the Kp value (Hl) value (Hl) increase is considered to be enhancement of disorder in the hydrophobic acyl chain regions of PC SUV membranes derived from the phenothiazine ring insertion and thus depends on the bulkiness of the substituent. The enthalpy-entropy correlation analysis yielding a good linear relationship also suggests that the phenothiazine drugs studied have identically an enthalpy-entropy compensation mechanism for the partitioning.

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“…4) We previously reported the partition coefficients (K p s) of some phenothiazine drugs including TFZ and CPZ for phosphatidylcholine (PC) small unilamellar vesicles (SUV) determined by second-derivative spectrophotometry. 5) The derivative method has been recognized to eliminate the effect of background signals 6,7) and usefully applied to the determination of the partition coefficients of drugs between lipid vesicles and water without the troublesome separation procedures [8][9][10] that may disturb the equilibrium states. Using SUV and large unilamellar vesicles (LUV) prepared from PC and cholesterol, the effects of vesicle size and cholesterol content in the bilayer membranes on the K p values of CPZ and TFZ were also studied by the second-derivative spectrophotometry.…”

mentioning

confidence: 99%

Effects of Phosphatidylserine and Phosphatidylethanolamine Content on Partitioning of Triflupromazine and Chlorpromazine between Phosphatidylcholine-Aminophospholipid Bilayer Vesicles and Water Studied by Second-Derivative Spectrophotometry

et al. 2005

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Partition coefficients of drugs between lipid bilayer vesicles (liposomes) and water provide fundamental information relating to the drug interactions with biomembranes. Especially, information on the drug partitioning helps understanding the pharmacodynamics and pharmacokinetics of drugs, because most of drugs usually partition into cell membrane by passive diffusion. In the quantitative structure-activity relationship (QSAR) studies of drugs, it has been suggested that the partition coefficients obtained for the liposome system are more effective than those obtained for the n-octanol/water system. [1][2][3] Triflupromazine (TFZ) and chlorpromazine (CPZ) are known as major antipsychotropic drugs of the phenothiazine derivatives and exert their action by antagonizing neuronal D 2 receptor in the brain. Recently, CPZ has been shown to hold promise as a pharmacotherapeutic agent for prion-based afflictions.4) We previously reported the partition coefficients (K p s) of some phenothiazine drugs including TFZ and CPZ for phosphatidylcholine (PC) small unilamellar vesicles (SUV) determined by second-derivative spectrophotometry. 5)The derivative method has been recognized to eliminate the effect of background signals 6,7) and usefully applied to the determination of the partition coefficients of drugs between lipid vesicles and water without the troublesome separation procedures [8][9][10] that may disturb the equilibrium states. Using SUV and large unilamellar vesicles (LUV) prepared from PC and cholesterol, the effects of vesicle size and cholesterol content in the bilayer membranes on the K p values of CPZ and TFZ were also studied by the second-derivative spectrophotometry. 11)A recent fluorescence study by Chen et al. provides that the hydrophobic nature of CPZ drives its general association with membranes, while the cationic nature of CPZ promotes its preferential association with phosphatidylserine (PS) in the bilayer membranes.12) Also, Elferink 13) and Dachary-Prigent 14) reported that CPZ bound preferentially to PC liposomes containing PS, compared to PC liposomes.PS is contained abundantly in the brain and nerve cell membranes as compared to the other organs. While phosphatidylethanolamine (PE), an aminophospholipid as PS and the second major phospholipid component after PC, is distributed widely all over the organs in the body and concerned with the membrane fusion and permeability.Therefore, the effects of these aminophospholipids, PS and PE, on the interactions of phenothiazine drugs with phospholipid bilayer vesicles should be investigated quantitatively, since the quantitative evaluation of the difference in the affinity of the drugs for PC, PS and PE will offer important information to understand their distribution and accumulation in the body.In this study we examined the effects of aminophospholipid contents and vesicle size on the partitioning of TFZ and CPZ into the vesicles (SUV and LUV) by using second-derivative spectrophotometry. Experimental Calculation of Molar Partition CoefficientsThe mol...

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Differential binding of chlorpromazine to human blood cells: Application of the hygroscopic desorption method

Cited by 26 publications

References 13 publications

Fatty-acid spin probe interactions with erythrocyte ghosts and liposomes prepared from erythrocyte ghosts

Fatty-acid spin probe interactions with erythrocyte ghosts and liposomes prepared from erythrocyte ghosts

Thermodynamics of Partitioning of Phenothiazine Drugs between Phosphatidylcholine Bilayer Vesicles and Water Studied by Second-Derivative Spectrophotometry

Effects of Phosphatidylserine and Phosphatidylethanolamine Content on Partitioning of Triflupromazine and Chlorpromazine between Phosphatidylcholine-Aminophospholipid Bilayer Vesicles and Water Studied by Second-Derivative Spectrophotometry

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