| Autor: |
Presa MH; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Rocha MJD; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Pires CS; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Ledebuhr KNB; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Costa GPD; Laboratory of Clean Organic Synthesis (LASOL), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Alves D; Laboratory of Clean Organic Synthesis (LASOL), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Bortolatto CF; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil., Brüning CA; Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Postgraduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), P.O. Box 354, 96010-900 Pelotas, Rio Grande do Sul, Brazil. |
| Abstrakt: |
Major depressive disorder (MDD) is a psychiatric disorder that affects a large portion of the population, with dysregulation of the serotonergic system, which is deeply involved in both the pathophysiology of MDD and mechanism of action of many antidepressants. Current pharmacological therapies do not meet the neurobiological needs of all depressed individuals, making the development of new antidepressants necessary. In recent decades, compounds containing triazoles have become promising due to their range of biological activities, including antidepressant activity. In this study, we evaluated the antidepressant-like effect of a hybrid containing triazole and acetophenone, 1-(2-(4-(4-ethylphenyl)-1 H -1,2,3-triazol-1-yl)phenyl)ethan-1-one (ETAP) (0.5-5 mg/kg), in the forced swimming test (FST) and tail suspension test (TST) in mice, as well as the involvement of the serotonergic system in this effect. Our findings demonstrated that ETAP exhibited an antidepressant-like effect from the dose of 1 mg/kg and that this effect is modulated by 5-HT 2A/2C and 5-HT 4 receptors. We also demonstrated that this effect may be related to inhibition of monoamine oxidase A activity in the hippocampus. Additionally, we evaluated the in silico pharmacokinetic profile of ETAP, which predicted its penetration into the central nervous system. ETAP exhibited a low potential for toxicity at a high dose, making this molecule interesting for the development of a new therapeutic strategy for MDD. |
