Inhibition of Aquaporin 4 by antiepileptic drugs

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

doi:10.1016/j.bmc.2007.12.038

Inhibition of Aquaporin 4 by antiepileptic drugs

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

Neurology

Research output: Contribution to journal › Article › peer-review

95 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 language	English (US)
Pages (from-to)	418-424
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2007.12.038
State	Published - 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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10.1016/j.bmc.2007.12.038

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AU - Kwee, Ingrid

AU - Nakada, Tsutomu

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KW - Drug design

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Inhibition of Aquaporin 4 by antiepileptic drugs

Abstract

Keywords

ASJC Scopus subject areas

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