N-(3-((3-(三氟甲基)苯基)硒基)丙-2-炔-1-基)苯甲酰胺可诱导小鼠产生抗抑郁样作用：涉及 5-羟色胺能系统。

N-(3-((3-(trifluoromethyl)phenyl)selanyl)prop-2-yn-1-yl) benzamide induces antidepressant-like effect in mice: involvement of the serotonergic system.

机构信息

Laboratory of Biochemistry and Molecular Neuropharmacology (LABIONEM), Graduate Program in Biochemistry and Bioprospecting (PPGBBio), Chemical, Pharmaceutical and Food Sciences Center (CCQFA), Federal University of Pelotas (UFPel), Capão do Leão Campus, Pelotas, RS, 96010-900, Brazil.

Nucleus of Synthesis and Application of Organic and Inorganic Compounds (NUSAACOI), Federal University of Fronteira Sul (UFFS), Campus Cerro Largo,, Cerro Largo, RS, Brazil.

出版信息

Psychopharmacology (Berl). 2024 Aug;241(8):1663-1678. doi: 10.1007/s00213-024-06588-8. Epub 2024 Apr 18.

DOI:10.1007/s00213-024-06588-8

PMID:38635075

Abstract

RATIONALE

Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects.

OBJECTIVE

To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CFSePB) in mice and the involvement of the serotonergic and noradrenergic systems.

METHODS

Male Swiss mice were treated with CFSePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CFSePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT receptor antagonist), prazosin (1 mg/kg, i.p., an α-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CFSePB (50 mg/kg, i.g.), and after 30 min of CFSePB administration the FST was performed.

RESULTS

CFSePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT and 5-HT receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CFSePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice.

CONCLUSION

This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

摘要

背景

重度抑郁症（MDD）显著降低了患者的生活质量。尽管 MDD 的确切病因尚不完全清楚，但单胺类物质（尤其是 5-羟色胺和去甲肾上腺素）的缺乏已被广泛接受。人们经常观察到对长期治疗的耐药性和不良反应，这突出表明需要新的药理学治疗方法。含有硒的合成有机化合物已表现出药理学特性，包括潜在的抗抑郁作用。

目的

评估 N-(3-((3-(三氟甲基)苯基)硒基)丙-2-炔-1-基)苯甲酰胺（CFSePB）在小鼠中的抗抑郁样作用，以及该作用是否与 5-羟色胺能和去甲肾上腺素能系统有关。

方法

雄性瑞士小鼠给予 CFSePB（1-50mg/kg，灌胃），30 分钟后进行强迫游泳试验（FST）或悬尾试验（TST）。为了研究 CFSePB 的抗抑郁样作用是否与 5-羟色胺能和去甲肾上腺素能系统有关，预先给予 CFSePB（50mg/kg，灌胃）的小鼠给予 p-CPA（5-HT 耗竭剂，100mg/kg，腹腔注射）或 5-HT 受体拮抗剂 WAY100635（0.1mg/kg，皮下注射）、酮色林（1mg/kg，腹腔注射，5-HT 受体拮抗剂）、昂丹司琼（1mg/kg，腹腔注射，5-HT 受体拮抗剂）、GR110838（0.1mg/kg，腹腔注射，5-HT 受体拮抗剂）、哌唑嗪（1mg/kg，腹腔注射，α-肾上腺素能受体拮抗剂）、育亨宾（1mg/kg，腹腔注射，α-肾上腺素能受体拮抗剂）和普萘洛尔（2mg/kg，腹腔注射，非选择性β-肾上腺素能受体拮抗剂），在给予 CFSePB（50mg/kg，灌胃）之前特定时间点进行预处理，在给予 CFSePB 30 分钟后进行 FST。