The location of amantadine hydrochloride and free base within phospholipid multilayers: a neutron and X-ray diffraction study

K. C. Duff, A. J. Cudmore, J. P. Bradshaw

Research output: Contribution to journalArticlepeer-review

Abstract

Concomitant neutron and X-ray studies were undertaken in order to locate accurately the anti-influenza and Parkinson's disease drug amantadine in multilayers of 1,2-dioleoyl-sn-glycero-3-phosphocholine. The X-ray data were phased using the swelling series method and the neutron data were phased using D2O/H2O exchange and a variation of the isomorphous replacement technique. The sets of data complement each other and reveal two populations of amantadine within the bilayer. One site is close to the bilayer surface, the other is much deeper. The majority of the amantadine occupies the surface site. The relative occupancy, but not the position, of the two locations appears to be dependent upon the initial protonation state of the drug. No evidence of bilayer pertubation was observed with either the protonated or the deprotonated forms of amantadine.

Original languageEnglish
Pages (from-to)149-156
Number of pages8
JournalBBA - Biomembranes
Volume1145
Issue number1
DOIs
Publication statusPublished - 18 Jan 1993

Funding

UK) who also read and made helpful comments on the manuscript. Neutron data collection and initial reduction were performed on instrument DI6 at the Institut Max von Laue - Paul Langevin, Grenoble, France. The work was supported by both SERC and ILL grants.

Keywords

  • Amantadine free base
  • Amantadine hydrochloride
  • NMR, H-
  • Phospholipid multilayer
  • X-ray diffraction

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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