Abstract
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.
Combinatorial Chemistry & High Throughput Screening
Title:Is There a Relationship Between Sweet Taste and Seizures? Anticonvulsant and Proconvulsant Effects of Non-Nutritive Sweeteners
Volume: 18 Issue: 4
Author(s): Mauricio E. Di Ianni, Andrea V. Enrique, Maria E. Del Valle, Blanca Aldana, María A. Rosella, Luisa Rocha, Eduardo A. Castro, Luis E. Bruno-Blanch and Alan Talevi
Affiliation:
Keywords: Drug repositioning, epilepsy, maximal electroshock seizures, non-nutritive sweeteners, pentylenetetrazol, stevia, Stevia rebaudiana, steviosides, convulsions, Swanson’s ABC model, virtual screening.
Abstract: 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.
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Cite this article as:
Ianni E. Di Mauricio, Enrique V. Andrea, Valle E. Del Maria, Aldana Blanca, Rosella A. María, Rocha Luisa, Castro A. Eduardo, Bruno-Blanch E. Luis and Talevi Alan, Is There a Relationship Between Sweet Taste and Seizures? Anticonvulsant and Proconvulsant Effects of Non-Nutritive Sweeteners, Combinatorial Chemistry & High Throughput Screening 2015; 18 (4) . https://dx.doi.org/10.2174/1386207318666150305154210
DOI https://dx.doi.org/10.2174/1386207318666150305154210 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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