CONICET | Buscador de Institutos y Recursos Humanos

Epilepsy is the most common central nervous system chronic disorder, affecting about 50 million worldwide, 90% of which come from developing countries (WHO, 2009). Current antiepileptic chemotherapy fails to protect against seizures in around 30% of the patients, a condition known as refractory or intractable epilepsy. What is more, current antiepileptic medications elicit a number of side effects that justify the continuous search of novel treatments. Drug repurposing implies finding second (or further) medical uses to known medications. It is an interesting concept, since known drugs have already undergone extensive safety studies, which may facilitate the approval of new therapeutic uses. Although historically most second medical uses have been found by serendipity, a number of authors have recently pointed out the possibilities of knowledge-based drug repurposing (Glan et al., 2011, Talevi et al., 2011, Deftereos et al., 2011, Lussier & Chen, 2011) (using computer models, bioinformatics and high-throughput literature searching to propose new medical indications for already known chemicals). We have previously reported a computational model to identify antiepileptic agents (Talevi et al., 2007a, 2007b). Recently, application of that model in virtual screening indicated that several artificial sweeteners, such as acesulfame, saccharin and cyclamate, might have anticonvulsant activity. Pharmacological testing in the Maximal Electroshock Seizure (MES) test has confirmed these predictions, which led us to propose what we have called ?the sweetener hypothesis?, i.e. the existence of an structural link between the receptor that mediates the sweet response in the mouth and any of the antiepileptic drug targets in the brain. This hypothesis might explain why a number of artificial sweeteners manifest anticonvulsant activity in the MES test.

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