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Solution Dynamics of Imipramine and Amitriptyline in Phospholipid Vesicles as Studied by 1H and 13C NMR

✍ Scribed by Marco G. Casarotto; David J. Craik

Publisher
Elsevier Science
Year
1993
Tongue
English
Weight
345 KB
Volume
158
Category
Article
ISSN
0021-9797

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✦ Synopsis

The solution dynamics of the interaction of the tricyclic antidepressant (TCA) drugs imipramine and amitriptyline with (\mathrm{L}-) (\alpha)-dipalmitoylphosphatidylcholine (DPPC) vesicles have been investigated by ({ }^{13} \mathrm{C}) and ({ }^{1} \mathrm{H}) NMR spectroscopy. Two- and onedimensional '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. ({ }^{13} \mathrm{C}) NMR relaxation parameters, including (T_{1}) (the spin-lattice relaxation time) and NOE, were measured for (\mathrm{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 ({ }^{13} \mathrm{C}) relaxation data. (e) 1993 Academic Press, Inc.

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