Investigation of the interaction mode of phenothiazine neuroleptics with alpha 1-acid glycoprotein.
The interaction of phenothiazine neuroleptics with alpha 1-acid glycoprotein (AGP) and desialylated AGP (asialoAGP) has been investigated by fluorescence, circular dichroism spectroscopy and by equilibrium dialysis. The binding parameters of phenothiazines obtained from fluorescence agreed closely with those obtained from circular dichroism and equilibrium dialysis. The binding affinities (nK) to AGP were slightly higher than binding affinities to asialoAGP. Attempts to correlate binding affinities with partition coefficients suggested that hydrophobic forces were mainly involved in the binding of phenothiazine neuroleptics to AGP and asialoAGP. However, electrostatic interaction was also found to be involved as suggested by experimental data obtained from the influence of oleic acid and caesium chloride on the drug binding to the two proteins.
Faculty of Pharmaceutical Science, Kumamoto University, Japan.
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T
Miyoshi
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Sukimoto
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M
Otagiri
D014150:Antipsychotic Agents / Q000493:pharmacokinetics*; D001212:Asialoglycoproteins / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002942:Circular Dichroism; D003956:Dialysis; D006801:Humans; D009961:Orosomucoid / Q000493:pharmacokinetics*; D010640:Phenothiazines; D011485:Protein Binding; D012044:Regression Analysis; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
D014150:Antipsychotic Agents; D001212:Asialoglycoproteins; D009961:Orosomucoid; D010640:Phenothiazines