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棕榈酮具有类似苯二氮䓬类药物的抗焦虑样作用和定量脑电图特征,其作用类似于丁螺环酮而非地西泮等临床药物。

Anxiolytic-like Effects and Quantitative EEG Profile of Palmitone Induces Responses Like Buspirone Rather Than Diazepam as Clinical Drugs.

机构信息

Laboratorio de Neurofarmacología de Productos Naturales, Dirección de Investigaciones en Neurociencias, Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Calz. México-Xochimilco 101, Col. San Lorenzo Huipulco, Tlalpan, Ciudad de México 14370, Mexico.

Biología Experimental, Universidad Autónoma Metropolitana, Ciudad de México 09340, Mexico.

出版信息

Molecules. 2023 Apr 24;28(9):3680. doi: 10.3390/molecules28093680.

Abstract

Anxiety is a mental disorder with a growing worldwide incidence due to the SARS-CoV-2 virus pandemic. Pharmacological therapy includes drugs such as benzodiazepines (BDZs) or azapirones like buspirone (BUSP) or analogs, which unfortunately produce severe adverse effects or no immediate response, respectively. Medicinal plants or their bioactive metabolites are a shared global alternative to treat anxiety. Palmitone is one active compound isolated from species due to its tranquilizing activity. However, its influence on neural activity and possible mechanism of action are unknown. In this study, an electroencephalographic (EEG) spectral power analysis was used to corroborate its depressant activity in comparison with the anxiolytic-like effects of reference drugs such as diazepam (DZP, 1 mg/kg) and BUSP (4 mg/kg) or 8-OH-DPAT (1 mg/kg), alone or in the presence of the GABA (picrotoxin, PTX, 1 mg/kg) or serotonin 5-HT receptor antagonists (WAY100634, WAY, 1 mg/kg). The anxiolytic-like activity was assayed using the behavioral response of mice employing open-field, hole-board, and plus-maze tests. EEG activity was registered in both the frontal and parietal cortex, performing a 10 min baseline and 30 min recording after the treatments. As a result, anxiety-like behavior was significantly decreased in mice administered with palmitone, DZP, BUSP, or 8-OH-DPAT. The effect of palmitone was equivalent to that produced by 5-HT receptor agonists but 50% less effective than DZP. The presence of PTX and WAY prevented the anxiolytic-like response of DZP and 8-OH-DPAT, respectively. Whereas only the antagonist of the 5-HT receptor (WAY) inhibited the palmitone effects. Palmitone and BUSP exhibited similar changes in the relative power bands after the spectral power analysis. This response was different to the changes induced by DZP. In conclusion, brain electrical activity was associated with the anxiolytic-like effects of palmitone implying a serotoninergic rather than a GABAergic mechanism of action.

摘要

焦虑是一种精神障碍,由于 SARS-CoV-2 病毒大流行,其全球发病率不断上升。药物治疗包括苯二氮䓬类药物(BDZ)或阿扎哌隆类药物,如丁螺环酮(BUSP)或类似物,但不幸的是,它们分别会产生严重的不良反应或没有立即产生反应。药用植物或其生物活性代谢物是治疗焦虑的全球共同替代品。棕榈酮是从 种中分离出的一种活性化合物,因其具有镇静作用而受到关注。然而,其对神经活动的影响及其可能的作用机制尚不清楚。在这项研究中,我们使用脑电图(EEG)频谱功率分析来证实其与参考药物(如地西泮(DZP,1mg/kg)和 BUSP(4mg/kg)或 8-OH-DPAT(1mg/kg))的抗焦虑样作用相比的抑制活性,单独或在 GABA(胡椒碱,PTX,1mg/kg)或 5-羟色胺 5-HT 受体拮抗剂(WAY100634,WAY,1mg/kg)存在的情况下。使用开放场、洞板和加迷宫测试来检测抗焦虑样活性。在治疗后进行 10 分钟基线和 30 分钟记录,记录前额叶和顶叶皮层的 EEG 活动。结果表明,棕榈酮、DZP、BUSP 或 8-OH-DPAT 给药的小鼠焦虑样行为显著减少。棕榈酮的作用与 5-HT 受体激动剂产生的作用相当,但比 DZP 有效 50%。PTX 和 WAY 的存在分别阻止了 DZP 和 8-OH-DPAT 的抗焦虑样反应。而只有 5-HT 受体拮抗剂(WAY)抑制了棕榈酮的作用。棕榈酮和 BUSP 在频谱功率分析后表现出相似的相对功率带变化。这种反应与 DZP 诱导的变化不同。总之,脑电活动与棕榈酮的抗焦虑样作用相关,表明其作用机制可能是 5-羟色胺能而不是 GABA 能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4e14/10180017/01a4d83099ae/molecules-28-03680-g001.jpg

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