In Silico Studies for the Analysis of Psychedelic Substances with Potential Activity for the Treatment of Epilepsy

Epilepsy is a neurological pathology, which affects approximately 70 million people, and affects individuals in their different conditions, whether age, social, geographic or racial limits. The pathophysiology of the disease hasn’t yet been fully established, however, it is believed that the seizures are triggered due to an imbalance between the excitatory mechanisms of glutamate associated with the lack of inhibition of this excessive excitation by the main inhibitory neurotransmitter, acid gamma-aminobutyric acid (GABA). In the market, there are several drugs available for the treatment of the disease, although, many do not reach the desired therapeutic effect. In this sense, the present work aims to apply in silico simulation to evaluate the activity of psychedelic molecules for the treatment of epilepsy. For this purpose, molecules were selected from databases for further evaluation of pharmacokinetic properties, through the Swiss ADME webserver. Not only pharmacological activity, toxicological prediction was also carried out, through the Protox-II and PreaADMET servers, with a view to evaluating the potential inactivity or activity for carcinogenicity, mutagenicity, hepatotoxicity and inhibition of the hERG gene. Activity and target/binder interaction were also predicted using the PASS prediction and SEA prediction webservers, respectively. For the study of molecular docking, with the purpose of evaluating the interaction of the ligands with the target GABA-aminotransferase (GABA-AT), the GOLD program was used as a tool. In the redocking step, Vigabatrin was used as the standard molecule, a drug used for the treatment of epilepsy and which acts by irreversibly inhibiting the GABA-AT enzyme. This, in turn, contributes to evaluating the interactions and types of interactions that occur between the ligand and the amino acid residues. Through the study, it is concluded that in relation to the pharmacokinetic and toxicological analyses, the results presented were satisfactory, since most of the molecules obtained good results in the absorption and distribution parameters, in addition to low toxicity. In the evaluation of biological activity, in the PASS prediction server, the majority showed anticonvulsant properties. Regarding docking, key interactions between ligands and target were observed. Therefore, the results of the study may in some way help in the discovery of new drugs for epilepsy.