title: Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors.
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.
authors.affiliation: Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata (UNLP), 47 & 115, La Plata B1900AJI, Buenos Aires, Argentina. atalevi@biol.unlp.edu.ar
authors.forename: Alan
authors.initials: A
authors.lastname: Talevi
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Enrique
authors.forename: Luis E
authors.initials: LE
authors.lastname: Bruno-Blanch
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D019295:Computational Biology; D003494:Cyclamates / Q000737:chemistry / Q000494:pharmacology; D058492:Drug Repositioning; D004597:Electroshock; D051379:Mice; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000737:chemistry* / Q000378:metabolism; D012439:Saccharin / Q000737:chemistry / Q000494:pharmacology; D012640:Seizures / Q000188:drug therapy / Q000209:etiology; D017386:Sequence Homology, Amino Acid; D013549:Sweetening Agents / Q000737:chemistry* / Q000494:pharmacology; D013649:Taste / Q000502:physiology; D055697:Taste Perception / Q000502:physiology; D013843:Thiazines / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000927:Anticonvulsants; D003494:Cyclamates; D043562:Receptors, G-Protein-Coupled; D018094:Receptors, Metabotropic Glutamate; D013549:Sweetening Agents; D013843:Thiazines; C431926:taste receptors, type 1; D012439:Saccharin; C006362:acetosulfame