Characterization of interactions of phenothiazines and related drugs with lipids by UV-spectrophotometry.
The UV-spectrum of chlorpromazine undergoes a red shift in the presence of vesicles of biological membranes or phospholipids, triglycerides, serum lipoproteins or fatty acids. The resulting difference spectrum has two positive peaks at about 260 and 320 nm and two negative peaks at 250 and 290 nm. This interaction signal, which was elicited in the presence of as little as 3 muM oleic acid, was dependent on the concentrations of both ligand and binder. It was abolished by 8 M urea, diminished by temperature increase up to 70 degrees C, but not changed by varying the ionic strength from 0 to 0.5. The chlorpromazine-triglyceride interaction signal was strongly enhanced with pH increasing from 6 to 10. The signal was only obtained with ligands fulfilling specific structural requirements, e.g., phenothiazines and most iminostilbenes, but not carbamazepine, imipramine, and amitriptyline.
D000818:Animals; D014150:Antipsychotic Agents / Q000032:analysis; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D002746:Chlorpromazine / Q000032:analysis; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008024:Ligands; D008055:Lipids / Q000032:analysis; D008862:Microsomes, Liver / Q000032:analysis; D008930:Mitochondria, Liver / Q000032:analysis; D009994:Osmolar Concentration; D011485:Protein Binding; D011506:Proteins; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D014508:Urea
D014150:Antipsychotic Agents; D008024:Ligands; D008055:Lipids; D011506:Proteins; D014508:Urea; D002746:Chlorpromazine