C-13 AND H-1-NMR STUDIES OF THE INTERACTION OF TRICYCLIC ANTIDEPRESSANT DRUGS WITH DODECYLDIMETHYLAMMONIUM CHLORIDE MICELLES

C-13 and H-1 NMR spectroscopy has been used to study the interaction of the tricyclic antidepressant (TCA) drugs imipramine and amitriptyline with dodecyldimethylammonium chloride (DDAC) micelles. C-13 NMR relaxation parameters, including T1 (the spin-lattice relaxation time) and NOE (the nuclear Overhauser effect), were measured at 75 and 100 MHz for mixtures of the TCA drugs and DDAC and were interpreted in terms of overall and internal motion of these micellar aggregates. NMR and fluorescence quenching experiments were used to determine the degree of partitioning of the drugs into the micelle in order to assist this interpretation. Under the conditions studied it was found that there is rapid exchange between free and micelle bound states and that the degree of partitioning of imipramine into the micelle (42%) is less than that for amitriptyline (76%). Both drugs were found to restrict the internal mobility of the micellar species, as evidenced by increased order parameters and correlation times for individual carbon sites in the DDAC alkyl chain on addition of drug. The drug molecules themselves were found to adopt an extended conformation in the micelle, with the dimethylammonium moiety residing close to the micelle surface and the tricyclic group penetrating the hydrophobic region of the micelle.