Inhibitory effect of phenothiazines on the binding of [3H]perazine to alpha 1-acid glycoprotein.
A system is described which allows the determination of the affinity constant of unlabelled drugs to alpha 1-acid glycoprotein (alpha 1-AGP) by displacing [3H]perazine from the binding protein with equilibrium dialysis. All drugs investigated appear to bind to only one site at the alpha 1-AGP molecule. From experiments, in which the chemical structure of the displacers was varied, the fragment 21-31 of the amino acid sequence appears to be a candidate for hydrophobic interactions. The glutamic acids 177 and 178 of the alpha 1-AGP molecule could be involved in ionic interactions with the side chain of phenothiazine derivatives. The relevance of alpha 1-AGP for drug binding, distribution, and the possible reasons for insufficient correlation between psychotropic plasma concentration and therapeutic response is discussed.
D014150:Antipsychotic Agents / Q000378:metabolism*; D001667:Binding, Competitive; D006863:Hydrogen-Ion Concentration; D009961:Orosomucoid / Q000378:metabolism*; D010464:Perazine / Q000378:metabolism*; D010640:Phenothiazines / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D014316:Tritium
D014150:Antipsychotic Agents; D009961:Orosomucoid; D010640:Phenothiazines; D014316:Tritium; D010464:Perazine