Identification of Anticonvulsant Activity of Widely-used Sweetener Acesulfame Potassium through Computacional Chemistry

ALAN TALEVI; LUIS E. BRUNO-BLANCH

Alejandría

Congreso; Biovision Alexandria 2010; 2010

Bibliotheca Alexandrian (BA) y The Academy of Sciences for the Developing Countries (TWAS)

Epilepsy is a chronic disorder of the brain characterized by recurrent seizures that can vary from the briefest lapses of attention or muscle jerks to severe, prolonged convulsions (violent and involuntary contractions of the muscles). The estimated proportion of the general population with active epilepsy (i.e. continuing seizures or the need for treatment) is between 4 to 10 per 1,000 people, although studies in developing countries suggest that the proportion is between 6 to 10 per 1,000. Around 50 million people in the world have epilepsy [1]. Virtual Screening, a set of computational approaches to search chemical databases in order to identify new therapeutic chemical agents, has been proved as an effective, inexpensive tool in drug discovery, with a huge potential in developing countries, where it can be applied in the identification of second uses of known drugs (also known as drug repurposing or reprofiling), giving response to urgent therapeutic needs in relatively short time and with relatively small costs [2]. Here we present the identification, through Virtual Screening based in molecular topology, of widely used artificial sweetener Acesulfame Potassium (approved by FDA for its use in soft drinks in 1998) [3] as a new anticonvulsant agent with remarkable anticonvulsant activity in the Maximal Electroshock Test from the Anticonvulsant Drug Development Program of the US National Health Institute [4]. Our preclinical results indicate a Time of Peak Effect of Acesulfame of 4 hours and an ED50 of 55.6 (sd = 19.3) (intraperitoneal, mice).