Inhibition of Aquaporin 4 by antiepileptic drugs

Vincent J. Huber, Mika Tsujita, Ingrid Kwee, Tsutomu Nakada

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

Abstract

The potential of antiepileptic drugs (AEDs) to inhibit the water transport properties of Aquaporin 4 (AQP4) was investigated using a combination of in silico and in vitro screening methods. Virtual docking studies on 14 AEDs indicated a range of docking energies that spanned approximately 40 kcal/mol, where the most stabilized energies were consistent with that of the previously identified AQP4 inhibitor acetazolamide. Nine AEDs and one bio-active metabolite were further investigated in a functional assay using AQP4 expressing Xenopus oocytes. Seven of the assayed compounds were found to inhibit AQP4 function, while three did not. A linear correlation was indicated between the in silico docking energies and the in vitro AQP4 inhibitory activity at 20 μM.

Original languageEnglish (US)
Pages (from-to)418-424
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2009

Keywords

  • Antiepileptic drugs
  • Aquaporin
  • Aquaporin 4
  • Drug design
  • Xenopus laevis oocytes

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

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