Inhibition of aquaporin 4 by antiepileptic drugs.
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 microM.
Huber
Vincent J
VJ
Center for Integrated Human Brain Science, Brain Research Institute, University of Niigata, 1 Asahimachi, Niigata 951-8585, Japan.
Tsujita
Mika
M
Kwee
Ingrid L
IL
Nakada
Tsutomu
T
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D051401:Aquaporin 4 / Q000037:antagonists & inhibitors*; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D006801:Humans; D009865:Oocytes; D011485:Protein Binding; D013816:Thermodynamics; D014981:Xenopus
D000927:Anticonvulsants; D051401:Aquaporin 4