Ferreira Maria Kueirislene Amâncio, da Silva Antônio Wlisses, Dos Santos Moura Atilano Lucas, Sales Ketelly Vanessa Barros, Marinho Emanuelle Machado, do Nascimento Martins Cardoso Joyce, Marinho Márcia Machado, Bandeira Paulo Nogueira, Magalhães Francisco Ernani Alves, Marinho Emmanuel Silva, de Menezes Jane Eire Silva Alencar, Dos Santos Hélcio Silva
State University of Ceará, Graduate Program in Natural Sciences, Natural Products Chemistry Laboratory, Fortaleza, Ceará, Brazil.
State University of Ceará, Northeaste Biotechnology Network, Fortaleza, Ceará, Brazil.
Epilepsy Behav. 2021 Apr;117:107881. doi: 10.1016/j.yebeh.2021.107881. Epub 2021 Mar 9.
In the treatment of anxiety and seizures, drugs of the benzodiazepine (BZD) class are used, which act on the Central Nervous System (CNS) through the neurotransmitter gamma-aminobutyric acid (GABA). Flavonoids modulate GABAA receptors. The aim of this study was to evaluate the anxiolytic and anticonvulsant effects of synthetic chalcones and their mechanisms of action via the GABAergic system, using adult zebrafish (ZFa). The animals were treated with chalcones (4.0 or 20 or 40 mg/kg; 20 µL; i.p) and submitted to the open field and 96 h toxicity test. Chalcones that cause locomotor alteration were evaluated in the light and dark anxiolytic test. The same doses of chalcones were evaluated in the anticonvulsant test. The lowest effective dose was chosen to assess the possible involvement in the GABAA receptor by blocking the flumazenil (fmz) antagonist. No chalcone was toxic and altered ZFa's locomotion. All chalcones had anxiolytic and anticonvulsant effects, mainly chalcones 1, where all doses showed effects in both tests. These effects were blocked by Fmz (antagonist GABAA), where it shows evidence of the performance of these activities of the GABA system. Therefore, this study demonstrated in relation to structure-activity, that the position of the substituents is important in the intensity of activities and that the absence of toxicity and the action of these compounds in the CNS, shows the pharmacological potential of these molecules, and, therefore, the insights are designed for the development of new drugs.
在焦虑症和癫痫的治疗中，会使用苯二氮䓬（BZD）类药物，这类药物通过神经递质γ-氨基丁酸（GABA）作用于中枢神经系统（CNS）。黄酮类化合物可调节GABAA受体。本研究的目的是使用成年斑马鱼（ZFa）评估合成查耳酮的抗焦虑和抗惊厥作用及其通过GABA能系统的作用机制。将动物用查耳酮（4.0或20或40mg/kg；20µL；腹腔注射）处理，并进行旷场试验和96小时毒性试验。对引起运动改变的查耳酮进行明暗箱抗焦虑试验评估。在抗惊厥试验中评估相同剂量的查耳酮。选择最低有效剂量通过阻断氟马西尼（fmz）拮抗剂来评估其对GABAA受体的可能参与情况。没有查耳酮有毒性并改变ZFa的运动。所有查耳酮都具有抗焦虑和抗惊厥作用，主要是查耳酮1，所有剂量在两项试验中均显示出效果。这些作用被Fmz（GABAA拮抗剂）阻断，这表明这些活动是通过GABA系统发挥作用的。因此，本研究在构效关系方面表明，取代基的位置对活性强度很重要，并且这些化合物在中枢神经系统中无毒性且有作用，显示了这些分子的药理潜力，因此，这些见解旨在用于开发新药。
