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5-HTR2B and SLC6A3 as potential molecular targets of sertraline in the treatment of major depressive disorder: the use of bioinformatics and its practical implication

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Abstract

Major depressive disorder (MDD) is known to be a highly limiting and disabling disorder worldwide. The main management for this disorder is based on pharmacological therapy with antidepressants, especially in moderate to severe presentations. Among these, selective serotonin reuptake inhibitors (SSRIs) are, at the moment, the most widely prescribed class. Individualized pharmacological therapy presents itself as a powerful tool to reduce the course of the disorder, especially if one takes into account the potential molecular targets and the relationship of these targets in MDD pharmacotherapy. To explore this possibility, using bioinformatics approaches, we combined two reverse molecular screening approaches, followed by traditional docking simulations to identify potential molecular targets specifically for sertraline. According to our results, sertraline presented 17 potential targets, 4 in common within both inverse screening approaches, and were analyzed in our study: 5-HTR2B (5-hydroxytryptamine receptor 2B subtype), SLC6A2 (norepinephrine transporter), SLC6A3 (dopamine transporter) and SLC6A4 (serotonin transporter). Traditional docking simulations revealed higher interaction energies of 5-HTR2B and SLC6A3 with the sertraline molecule. In addition, both proteins are directly or indirectly related to the modulation of serotonin and dopamine, as well as the rate of response to SSRIs. Therefore, we suggest that the interaction of sertraline with the 5-HTR2B and SLC6A3 proteins points to a multimodal mechanism of pharmacological action, especially for the treatment of MDD.

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Acknowledgements

This work was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant number: 407537/2018); the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, financial code 001).

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de Oliveira, R.R., Kuhn, D., Heidrich, D. et al. 5-HTR2B and SLC6A3 as potential molecular targets of sertraline in the treatment of major depressive disorder: the use of bioinformatics and its practical implication. Netw Model Anal Health Inform Bioinforma 11, 34 (2022). https://doi.org/10.1007/s13721-022-00378-y

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