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Anxiolytic-like action of 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) in mice: A possible contribution of the serotonergic system
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2023-10-02 , DOI: 10.1016/j.pbb.2023.173651
Larissa Sander Magalhães 1 , Dianer Nornberg Strelow 1 , Mariana Parron Paim 1 , Taís da Silva Teixeira Rech 1 , Letícia Devantier Krüger 1 , Antonio Luiz Braga 2 , José Sebastião Santos Neto 3 , César Augusto Brüning 1 , Cristiani Folharini Bortolatto 1
Affiliation  

Anxiety disorders, characterized by high prevalence rates, cause psychiatric disabilities and are related to impairments in serotoninergic system function. Frequent anxiety recurrence, resistance, and drug adverse effects have driven searches for new therapies. We initially evaluated the anxiolytic-like activity of 3-selanyl-benzo[b]furan compounds (SeBZF1–5) (50 mg/kg, i.g.) in male Swiss mice using the light-dark test (LDT). The compound 3-((4-methoxyphenyl)selanyl)-2-phenylbenzofuran (SeBZF3) exhibited anxiolytic-like activity. SeBZF3 anxiolytic-like effects were also observed in the novelty-suppressed feeding test (NSFT) (50 mg/kg) and elevated plus-maze test (EPMT) (25 and 50 mg/kg). In the EPMT, anxiolytic-like effects of SeBZF3 (50 mg/kg) were abolished by pretreatment with p-chlorophenylalanine, a selective tryptophan hydroxylase inhibitor (100 mg/kg, i.p. for 4 days), suggesting the involvement of serotonergic mechanisms. Furthermore, we conducted experiments to investigate the synergistic effects of SeBZF3 subeffective doses (5 mg/kg, i.g.) in combination with fluoxetine (a selective serotonin reuptake inhibitor, 5 mg/kg, i.p.) or buspirone (a partial agonist of the 5-HT1A receptor, 2 mg/kg, i.p.). This coadministration resulted in pronounced synergistic effects. We also examined the effects of repeated oral treatment with SeBZF3 at doses of 1 and 5 mg/kg over 14 days and both reduced anxiety signals. In vitro and ex vivo findings revealed that SeBZF3 inhibited cerebral MAO-A activity. These findings collectively imply the potential involvement of serotonergic mechanisms in the anxiolytic-like activity of SeBZF3 in mice. These data offer contributions to the research field of organoselenium compounds and anxiolytics, encouraging the broadening of the search for new effective drugs while offering improved side effect profiles.



中文翻译:

3-((4-甲氧基苯基)硒基)-2-苯基苯并呋喃 (SeBZF3) 对小鼠的抗焦虑样作用:血清素系统的可能贡献

焦虑症的特点是发病率高,会导致精神障碍,并与血清素能系统功能损伤有关。频繁的焦虑复发、耐药性和药物不良反应推动了对新疗法的寻找。我们最初使用明暗试验 (LDT)评估了 3-硒基-苯并[ b ]呋喃化合物 (SeBZF 1-5 ) (50 mg/kg, ig) 在雄性瑞士小鼠中的抗焦虑样活性。化合物3-((4-甲氧基苯基)硒基)-2-苯基苯并呋喃(SeBZF 3 )表现出抗焦虑样活性。在新奇抑制喂养试验(NSFT)(50 mg/kg)和高架十字迷宫试验(EPMT)(25 和 50 mg/kg)中也观察到 SeBZF 3 抗焦虑样作用在 EPMT 中,SeBZF 3 (50 mg/kg) 的抗焦虑样作用被对氯苯丙氨酸(一种选择性色氨酸羟化酶抑制剂,100 mg/kg,腹腔注射 4 天)预处理所消除,表明涉及血清素能机制。此外,我们还进行了实验来研究 SeBZF 3亚有效剂量(5 mg/kg,ig)与氟西汀(一种选择性血清素再摄取抑制剂,5 mg/kg,腹膜内注射)或丁螺环酮( 5 羟色胺的部分激动剂)联合使用的协同效应。 -HT 1A受体,2 mg/kg,腹膜内注射)。这种共同给药产生了显着的协同效应。我们还研究了在 14 天内以 1 和 5 mg/kg 剂量重复口服 SeBZF 3的效果,以及两者均减少焦虑信号。体外离体研究结果表明,SeBZF 3抑制大脑 MAO-A 活性。这些发现共同表明血清素能机制可能参与小鼠SeBZF 3的抗焦虑样活性。这些数据为有机硒化合物和抗焦虑药的研究领域做出了贡献,鼓励扩大对新有效药物的探索,同时改善副作用。

更新日期:2023-10-06
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