Binding of several phenothiazine neuroleptics to a common binding site of alpha 1-acid glycoprotein, orosomucoid
- Resource Type
- Authors
- El-Gamal Safaa; Walter E. Müller; Uwe Wollert
- Source
- Journal of pharmaceutical sciences. 72(2)
- Subject
- Circular dichroism
Stereochemistry
Pharmaceutical Science
Orosomucoid
chemistry.chemical_compound
Structure-Activity Relationship
Single site
Phenothiazines
Phenothiazine
medicine
Humans
Binding site
Chlorpromazine
chemistry.chemical_classification
Binding Sites
biology
Chemistry
Circular Dichroism
Biochemistry
α1 acid glycoprotein
biology.protein
Glycoprotein
Dialysis
medicine.drug
Antipsychotic Agents
Protein Binding
- Language
- ISSN
- 0022-3549
The interaction of several phenothiazine neuroleptics with alpha 1-acid glycoprotein was investigated using circular dichroism and equilibrium dialysis techniques. For chlorpromazine only, one high-affinity binding site of the protein was found. The binding of the drug to this single site generated typical polyphasic extrinsic Cotton effects. Since several other phenothiazine neuroleptics gave qualitatively comparable extrinsic Cotton effects in the presence of alpha 1-acid glycoprotein and potently inhibited the binding of chlorpromazine to the single site, it was concluded that all phenothiazine derivatives investigated bound preferentially to only one common binding site of the alpha 1-acid glycoprotein molecule.