Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice

Rocha, Marcia Juciele da; Pires, Camila Simões; Presa, Marcelo Heinemann; Besckow, Evelyn Mianes; Nunes, Gustavo D’Avila; Gomes, Caroline Signorini; Penteado, Filipe; Lenardão, Eder J.; Bortolatto, Cristiani F.; Brüning, César Augusto

doi:10.1007/s00213-023-06313-x

Cited by 8 publications

(5 citation statements)

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“…These results reinforce the observed antioxidant potential of these compounds. Our research group recently published data on the antidepressant-like effect of SeI and MeSeI, and their involvement with the serotonergic system ( Garcia et al, 2022 ; da Rocha et al, 2023 ). In these studies, it was observed for the first time the antidepressant-like effect of oral acute administration of chalcogen-indolizines, in male Swiss mice.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, to better elucidate the mechanism of action of these substances in animals, it is necessary to carry out preclinical induction protocols. Additionally, there is a need to evaluate the toxicity of these compounds, although previous behavioral tests with SeI and MeSeI showed low toxicity in rodents ( Garcia et al, 2022 ; da Rocha et al, 2023 ), which provides initial insights into the compounds’ safety profile.…”

Section: Discussionmentioning

confidence: 99%

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Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays

Garcia,

da Rocha,

Presa

et al. 2024

PeerJ

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Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive molecules produced naturally by the body and by external factors. When these species are generated in excessive amounts, they can lead to oxidative stress, which in turn can cause cellular and tissue damage. This damage is known to contribute to the aging process and is associated with age-related conditions, including cardiovascular and neurodegenerative diseases. In recent years, there has been an increased interest in the development of compounds with antioxidant potential to assist in the treatment of disorders related to oxidative stress. In this way, compounds containing sulfur (S) and/or selenium (Se) have been considered promising due to the relevant role of these elements in the biosynthesis of antioxidant enzymes and essential proteins with physiological functions. In this context, studies involving heterocyclic nuclei have significantly increased, notably highlighting the indolizine nucleus, given that compounds containing this nucleus have been demonstrating considerable pharmacological properties. Thus, the objective of this research was to evaluate the in vitro antioxidant activity of eight S- and Se-derivatives containing indolizine nucleus and different substituents. The in vitro assays 1,1-diphenyl-2-picryl-hydrazil (DPPH) scavenger activity, ferric ion (Fe3+) reducing antioxidant power (FRAP), thiobarbituric acid reactive species (TBARS), and protein carbonylation (PC) were used to access the antioxidant profile of the compounds. Our findings demonstrated that all the compounds showed FRAP activity and reduced the levels of TBARS and PC in mouse brains homogenates. Some compounds were also capable of acting as DPPH scavengers. In conclusion, the present study demonstrated that eight novel organochalcogen compounds exhibit antioxidant activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays

Garcia,

da Rocha,

Presa

et al. 2024

PeerJ

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“…Over the last decade, there has been a rapid increase in CADD-based studies of depression, including docking studies of ligands for serotonin reuptake [171,172], MAO A and MAO B [173,174], dual action on MAO-B/AChE [175], glycogen synthase kinase [176], sodium hNaV1.2 or hNaV1.7 channels [177], serotonin receptors (5HT1A, 5-HT2A, 5-HT2C and 5-HT4) [171,[178][179][180][181], adenosine A1/A2A receptors [182], T-type calcium channels [183], tryptophan 2,3-dioxygenase [184] and sigma receptor [185]. Similarly, application of docking in psychoses involved ligands for serotonin 5HT2 and dopamine D2 receptors [186], α4β2 and α7 nicotinic acetylcholine receptors [187,188], phosphodiesterase 10A [189], MAO A and B [190], a syntaxin-binding protein (STXBP1) [191], NMDA type subunit 1 (GRIN1) [192], fatty acid binding protein 7 (FABP7) [193,194], metabotropic glutamate mGluR5 receptor [195], ionotropic GABA-A receptor [196], glycine transporter type 1 (GlyT1) [197] and kynurenine aminotransferase II (KATII) [198].…”

Section: In Silico-driven Search For Novel Therapeutic Agentsmentioning

confidence: 99%

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Kositsyn

Abreu

Колесникова

et al. 2023

IJMS

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Depression and schizophrenia are two highly prevalent and severely debilitating neuropsychiatric disorders. Both conventional antidepressant and antipsychotic pharmacotherapies are often inefficient clinically, causing multiple side effects and serious patient compliance problems. Collectively, this calls for the development of novel drug targets for treating depressed and schizophrenic patients. Here, we discuss recent translational advances, research tools and approaches, aiming to facilitate innovative drug discovery in this field. Providing a comprehensive overview of current antidepressants and antipsychotic drugs, we also outline potential novel molecular targets for treating depression and schizophrenia. We also critically evaluate multiple translational challenges and summarize various open questions, in order to foster further integrative cross-discipline research into antidepressant and antipsychotic drug development.

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“…N -(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide (SePB, Figure ) is a synthetic organic compound containing a selenium atom and a benzamide nucleus. Synthetic organic selenium compounds have been recognized for their pharmacological properties, including their antioxidant and analgesic effects. − Notably, some of these compounds have demonstrated antidepressant effects in preclinical trials. − At the same time, compounds containing a benzamide nucleus have antioxidant characteristics and anti-inflammatory, analgesic, and antidepressant properties. − The bond between the selenium atom and benzamide nucleus in the chemical structure of SePB has shown promising results in preclinical contexts, demonstrating a rapid antidepressant-like effect in male and female mice, with the participation of the serotonergic system through the 5-HT 1A , 5-HT 2 A /2C , 5-HT 3 , and 5-HT 4 receptors. , …”

Section: Introductionmentioning

confidence: 99%

Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide

Besckow,

Ledebuhr,

Pires

et al. 2024

ACS Chem. Neurosci.

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The compound N- (3-(phenylselanyl)prop-2-yn-1yl)benzamide (SePB), which combines a selenium atom and a benzamide nucleus in an organic structure, has demonstrated a fast antidepressant-like effect in mice. This action is influenced by the serotonergic system and represents a promising development in the search for novel antidepressant drugs to treat major depressive disorder (MDD), which often resists conventional treatments. This study aimed to further explore the mechanism underlying the antidepressant-like effect of SePB by investigating the involvement of the dopaminergic and noradrenergic systems in the tail suspension test (TST) in mice and evaluating its pharmacokinetic profile in silico. Preadministration of the dopaminergic antagonists haloperidol (0.05 mg/kg, intraperitoneally (i.p.)), a nonselective antagonist of dopamine (DA) receptors, SCH23390 (0.01 mg/kg, subcutaneously (s.c.)), a D 1 receptor antagonist, and sulpiride (50 mg/kg, i.p.), a D 2/3 receptor antagonist, before SePB (10 mg/kg, intragastrically (i.g.)) prevented the anti-immobility effect of SePB in the TST, demonstrating that these receptors are involved in the antidepressant-like effect of SePB. Administration of the noradrenergic antagonists prazosin (1 mg/kg, i.p.), an α 1 -adrenergic antagonist, yohimbine (1 mg/kg, i.p.), an α 2 -adrenergic antagonist, and propranolol (2 mg/kg, i.p.), a β-adrenergic antagonist, did not block the antidepressant-like effect of SePB on TST, indicating that noradrenergic receptors are not involved in this effect. Additionally, the coadministration of SePB and bupropion (a noradrenaline/dopamine reuptake inhibitor) at subeffective doses (0.1 and 3 mg/kg, respectively) produced antidepressant-like effects. SePB also demonstrated good oral bioavailability and low toxicity in computational absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses. These findings suggest that SePB has potential as a new antidepressant drug candidate with a particular focus on the dopaminergic system.

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Involvement of the serotonergic system in the antidepressant-like effect of 1-(phenylselanyl)-2-(p-tolyl)indolizine in mice

Cited by 8 publications

References 77 publications

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays

Exploring the antioxidant potential of chalcogen-indolizines throughout in vitro assays

Towards Novel Potential Molecular Targets for Antidepressant and Antipsychotic Pharmacotherapies

Dopaminergic Modulation and Computational ADMET Insights for the Antidepressant-like Effect of N-(3-(Phenylselanyl)prop-2-yn-1-yl)benzamide

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