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.
Keywords: Drug repositioning, epilepsy, maximal electroshock seizures, non-nutritive sweeteners, pentylenetetrazol, stevia,
Stevia rebaudiana, steviosides, convulsions, Swanson’s ABC model, virtual screening.
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