Anticonvulsant activity of artificial sweeteners: A structural link between sweet-taste receptor T1R3 and brain glutamate receptors
- 作者：Alan Talevi ; atalevi@biol.unlp.edu.ar ; Andrea V. Enrique ; Luis E. Bruno-Blanch
- 关键词：Anticonvulant ; Epilepsy ; Sweetener ; T1R3 ; Virtual screening ; Knowledge-based drug repurposing
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：15 June, 2012
- 卷：22
- 期：12
- 页码：4072-4074
- 文件大小：219 K
摘要
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.