Is there a relationship between sweet taste and seizures? Anticonvulsant and proconvulsant effects of non-nutritive sweeteners.
From a virtual screening campaign, a number of artificial and natural sweeteners were predicted as potential anticonvulsant agents with protective effects in the seizure animal model Maximal Electroshock Seizure (MES) test. In all cases, the predictions were experimentally confirmed in the aforementioned preclinical seizure model. The article reviews and expands previous reports from our group on anticonvulsant activity of those non-nutritive sweeteners, illustrating the potential of virtual screening approaches to propose new medical uses of food additives. This constitutes a particular case of knowledge-based drug repositioning, which may greatly shorten the development time and investment required to introduce novel medications to the pharmaceutical market. We also briefly overview evidence on possible molecular explanations on the anticonvulsant and proconvulsant effects of different non-nutritive sweeteners. Our analysis -based on Swanson's ABC model- suggests that group I metabotropic glutamate receptors and carbonic anhydrase isoform VII (both proposed or validated molecular targets of antiepileptic drugs) might be involved in the anticonvulsant effect of artificial sweeteners. The first hypothesis is in line with recent advances on development of selective modulators of group I metabotropic glutamate receptors as potential antiepileptic agents.
Mauricio E
ME
Di Ianni
Andrea V
AV
Enrique
María E
ME
Del Valle
Blanca
B
Aldana
María A
MA
Rosella
Luisa
L
Rocha
Eduardo A
EA
Castro
Luis E
LE
Bruno-Blanch
Medicinal Chemistry, Department of Biological Sciences, Faculty of Exact Sciences, National University of La Plata, Buenos Aires, Argentina. atalevi@biol.unlp.edu.ar.
Alan
A
Talevi
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D064306:Non-Nutritive Sweeteners / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy*; D013649:Taste / Q000187:drug effects*
D000927:Anticonvulsants; D064306:Non-Nutritive Sweeteners