Membrane interactions of some catamphiphilic drugs and relation to their multidrug-resistance-reversing ability

Pajeva, Ilza; Wiese, Michael; Cordes, H. P.; Seydel, Joachim K.

doi:10.1007/bf01203070

Cited by 71 publications

(69 citation statements)

References 38 publications

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“…Pardridge et al 2 showed that influx of lidocaine to the brain is not restricted by the blood brain barrier. Pajeva et al 24 also reported that lidocaine does not interact with phospholipids constructing tumour cells expressing P-gp. The results of the present study are consistent with these reports.…”

Section: Measurement Of Lidocaine Megx and Bupivacaine In Plasma Andmentioning

confidence: 99%

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats

Funao

Oda

Tanaka

et al. 2003

Can J Anesth/J Can Anesth

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P Pu ur rp po os se e: : To examine whether inhibition of P-glycoprotein (P-gp) activity by quinidine affects the central nervous system toxicity of lidocaine and racemic bupivacaine (bupivacaine).M Me et th ho od ds s: : Forty male Sprague-Dawley rats were randomly divided into four groups (n = 10). Fifteen minutes following administration of 15 mg·kg ) was infused until convulsions occurred. Concentrations of lidocaine and its primary metabolite, monoethylglycinexylidide (MEGX) and bupivacaine in plasma and in the brain at the onset of convulsions were measured by high-performance liquid chromatography.R Re es su ul lt ts s: : There were no differences in the dose of lidocaine required to induce convulsions between the L and QL groups. There were no differences in the concentrations of total (L = 17.2 ± 3.5, QL = 16.6 ± 2.6 µg·mL ) in plasma, total lidocaine or MEGX in the brain at the onset of convulsions between the L and QL groups. The dose of bupivacaine required to induce convulsions was comparable in the B and QB groups. At the onset of convulsions, plasma concentrations of both total (B = 4.9 ± 1.1, QB = 4.0 ± 0.6 µg·mL -1 , P = 0.03) and unbound bupivacaine (B = 1.4 ± 0.6, QB = 0.9 ± 0.2 µg·mL -1 , P = 0.02) were significantly lower in the QB group than in the B group. There were no differences in concentration of total bupivacaine in the brain between the B and QB groups.C Co on nc cl lu us si io on n: : These results suggest that quinidine inhibited P-gp activity, resulting in increased brain/plasma concentration ratio of bupivacaine, but not of lidocaine, and decreased the threshold of plasma concentration for bupivacaine-induced convulsions. (L = 17,2 ± 3,5, QL = 16,6 ± 2, ) et libre (L = 7,8 ± 2,5, QL = 7,3 ± 2, ), entre le MEGX total (L = 1,2 ± 0,5, QL = 1,3 ± 0, ) et libre (L = 0,9 ± 0,5, QL = 0,8± 0,4 (B = 4,9 ± 1,1, QB = 4,0 ± 0, , P = 0,03) et libre (B = 1,4 ± 0,6, QB = 0,9 ± 0 The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats La quinidine, un inhibiteur de P-glycoprotéine, abaisse le seuil des convulsions induites par la bupivacaïne, mais non par la lidocaïne, chez les rats Objectif : Vérifier si l'inhibition de l'activité des P-glycoprotéines (P-gp

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Section: Measurement Of Lidocaine Megx and Bupivacaine In Plasma Andmentioning

confidence: 99%

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats

Funao

Oda

Tanaka

et al. 2003

Can J Anesth/J Can Anesth

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“…18,21 The compounds were diluted from high to low concentrations horizontally in the plates. Cells were seeded to each well (1x10 4 ) with the exception of medium control wells.…”

Section: Assay For Antiproliferative Effect / Checkerboard Microplatementioning

confidence: 99%

Saikosaponin A ve Saikosaponin D ile MCF-7/Pac Hücre Hattında Paklitaksel Dirençliliğinin Engellenmesi

Kars¹,

Kars²,

Gündüz³

2013

UHOD

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Cancer cells demonstrate multiple drug resistance phenotype frequently after chemotherapy. The resistance of cancer cells to various chemotherapeutic agents is defined as multiple drug resistance. The purpose of this study is to investigate the potential reversal effects of active agents, that are found high amount in plants, on resistant MCF-7 cell lines. The effects of potential MDR modulators combined with anticancer drugs were also evaluated. Flow cytometry, fluorescence microscopy and checkerboard combination assays were performed to study the reversal of drug resistance and for investigation of the antiproliferative effects of the combination of anticancer drugs with the modulators. Paclitaxel and potential MDR modulators (verapamil, saikosaponin A, D and isoquercitrin) were applied to the sublines in combination. Fluorescence accumulation levels and fractional inhibitory indices show that saikosaponin A and D are effective MDR reversal agents that may be used together with paclitaxel in drug resistant mammary carcinoma subline. In conclusion this report represents saikosaponin A and D from natural resources are valuable reagents that may improve the success of chemotherapy.

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“…P-glycoprotein and MRP1 are transmembrane proteins, and their activity can be dependent on the properties of the surrounding lipids (see [16,17] for review). The transport activity of P-gp can be modulated by detergents and other amphipathic compounds [18,19], suggesting that perturbation of the membrane structure rather than direct binding to the protein is likely to be the mechanism of action of at least some P-glycoprotein inhibitors [20][21][22][23]. Although P-gp and MRP1 are both transmembrane proteins, much less is known about the influence of membrane properties on MRP1 transport activity.…”

Section: Introductionmentioning

confidence: 99%

Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

Wesołowska

Hendrich

Łania-Pietrzak

et al. 2009

Cellular and Molecular Biology Letters

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The expression of transmembrane transporter multidrug resistance-associated protein 1 (MRP1) confers the multidrug-resistant phenotype (MDR) on cancer cells. Since the activity of the other MDR transporter, P-glycoprotein, is sensitive to membrane perturbation, we aimed to check whether the changes in lipid bilayer properties induced by flavones (apigenin, acacetin) and flavonols (morin, myricetin) were related to their MRP1 inhibitory activity. All the flavonoids inhibited the efflux of MRP1 fluorescent substrate from human erythrocytes and breast cancer cells. Morin was also found to stimulate the ATPase activity of erythrocyte ghosts. All flavonoids intercalated into phosphatidylcholine bilayers as judged by differential scanning calorimetry and fluorescence spectroscopy with the use of two carbocyanine dyes. The model of an intramembrane localization for flavones and flavonols was proposed. No clear relationship was found between the membrane-perturbing activity of flavonoids and their potency to inhibit MRP1. We concluded that mechanisms other than perturbation of the lipid phase of membranes were responsible for inhibition of MRP1 by the flavonoids.

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Membrane interactions of some catamphiphilic drugs and relation to their multidrug-resistance-reversing ability

Cited by 71 publications

References 38 publications

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats

The P-glycoprotein inhibitor quinidine decreases the threshold for bupivacaine-induced, but not lidocaine-induced, convulsions in rats

Saikosaponin A ve Saikosaponin D ile MCF-7/Pac Hücre Hattında Paklitaksel Dirençliliğinin Engellenmesi

Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

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