Abstract
The solution dynamics of the interaction of the tricyclic antidepressant (TCA) drugs imipramine and amitriptyline with L -α-dipalmitoylphosphatidylcholine (DPPC) vesicles have been investigated by 13C and 1H NMR spectroscopy. Two- and one-dimensional 1 H NOE (nuclear Overhauser effect) experiments have been used examine the conformation of the TCAs in DPPC vesicles. Both drug molecules were found to adopt a folded conformation with the dimethylammonium terminal group in close proximity to the tricyclic moiety. 13C NMR relaxation parameters, including T1 (the spin-lattice relaxation time) and NOE, were measured for TCA/vesicle solutions. These results support a folded conformation and also reveal a difference in the degree of partitioning of the two drugs within the vesicles. It is estimated by fluorescence quenching experiments that 45 and 85% of imipramine and amitriptyline, respectively, reside within the vesicle, which is in agreement with the 13C relaxation data.
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