Abstract
A virtual screening campaign based on application of a topological discriminant function capable of identifying novel anticonvulsant agents indicated several widely-used artificial sweeteners as potential anticonvulsant candidates. Acesulfame potassium, cyclamate and saccharin were tested in the Maximal Electroshock Seizure model (mice, ip), showing moderate anticonvulsant activity. We hypothesized a probable structural link between the receptor responsible of sweet taste and anticonvulsant molecular targets. Bioinformatic tools confirmed a highly significant sequence-similarity between taste-related protein T1R3 and several metabotropic glutamate receptors from different species, including glutamate receptors upregulated in epileptogenesis and certain types of epilepsy.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anticonvulsants / chemistry*
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Anticonvulsants / pharmacology
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Brain / metabolism*
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Computational Biology
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Cyclamates / chemistry
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Cyclamates / pharmacology
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Drug Repositioning*
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Electroshock
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Mice
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Protein Structure, Tertiary
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Receptors, G-Protein-Coupled / chemistry*
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Receptors, G-Protein-Coupled / metabolism
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Receptors, Metabotropic Glutamate / chemistry*
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Receptors, Metabotropic Glutamate / metabolism
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Saccharin / chemistry
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Saccharin / pharmacology
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Seizures / drug therapy
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Seizures / etiology
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Sequence Homology, Amino Acid
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Sweetening Agents / chemistry*
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Sweetening Agents / pharmacology
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Taste / physiology
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Taste Perception / physiology
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Thiazines / chemistry
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Thiazines / pharmacology
Substances
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Anticonvulsants
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Cyclamates
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Receptors, G-Protein-Coupled
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Receptors, Metabotropic Glutamate
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Sweetening Agents
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Thiazines
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taste receptors, type 1
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Saccharin
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acetosulfame