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载有尼莫地平的脂质体制剂的开发和评价及其在小鼠抗焦虑活性中的作用。

Development and evaluation of liposomal formulation containing nimodipine on anxiolytic activity in mice.

机构信息

Laboratory of Experimental Neurochemistry Research, Federal University of Piaui, Teresina, PI, Brazil; Immunopathology Keizo-Asami Laboratory, Federal University of Pernambuco, Recife, PE, Brazil.

Laboratory of Experimental Neurochemistry Research, Federal University of Piaui, Teresina, PI, Brazil.

出版信息

Pharmacol Biochem Behav. 2014 Jan;116:64-8. doi: 10.1016/j.pbb.2013.10.023. Epub 2013 Nov 4.

Abstract

Nimodipine has been investigated in the treatment of anxiety. Its administration, however, presents a number of limitations, particularly by low bioavailability, low aqueous solubility and photosensitivity. These difficulties can be resolved by the use of nanometer-scale pharmaceutical carriers. The goal of the present study was thus to develop a liposomal formulation containing nimodipine (NMD-Lipo) and evaluate anxiolytic activity using models of anxiety (open-field, light and dark and elevated plus-maze test). The results suggest that administration of NMD-Lipo has no sedative or muscle relaxant effect in animals, since there was no reduction in the number of crossings, grooming and rearings. The increased residence time of the animals treated with NMD-Lipo in the bright field is a reflection of the anxiolytic-like activity of the formulation. Furthermore, the reduction in residence time of rodents treated with the combination of flumazenil and NMD-Lipo in the illuminated box suggests that NMD-Lipo acts on benzodiazepine receptors. The increase in the number of entries and length of stay in the open arms of mice treated with NMD-Lipo suggests that anxiolytic activity of formulation and reduction in number of entries and length of stay in open arms of rodents treated with a combination of flumazenil and NMD-Lipo suggest that NMD-Lipo act on benzodiazepine receptors.

摘要

尼莫地平已被研究用于治疗焦虑症。然而,其应用存在一些限制,特别是生物利用度低、水溶性低和光敏感性。这些困难可以通过使用纳米级药物载体来解决。因此,本研究的目的是开发一种含有尼莫地平的脂质体制剂(NMD-Lipo),并使用焦虑症模型(旷场、明暗和高架十字迷宫试验)评估其抗焦虑活性。结果表明,NMD-Lipo 给药对动物没有镇静或肌肉松弛作用,因为动物的穿越、梳理和后肢次数没有减少。用 NMD-Lipo 治疗的动物在明亮场中的停留时间增加反映了该制剂的类抗焦虑活性。此外,用氟马西尼和 NMD-Lipo 联合治疗的啮齿动物在照明箱中的停留时间减少表明 NMD-Lipo 作用于苯二氮䓬受体。用 NMD-Lipo 治疗的小鼠进入和停留在开放臂的次数和时间增加表明该制剂具有抗焦虑活性,而用氟马西尼和 NMD-Lipo 联合治疗的啮齿动物进入和停留在开放臂的次数和时间减少表明 NMD-Lipo 作用于苯二氮䓬受体。

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