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Involvement of the serotoninergic system in the anxiolytic action mechanism of a liposomal formulation containing nimodipine (NMD-Lipo)
Pharmacology Biochemistry and Behavior ( IF 3.6 ) Pub Date : 2023-10-05 , DOI: 10.1016/j.pbb.2023.173654
Hellen Kelen Maria Medeiros Coimbra Viana 1 , George Laylson da Silva Oliveira 2 , Lina Clara Gayoso E Almendra Ibiapina Moreno 1 , Ana Amélia Carvalho de Melo-Cavalcante 2 , Maurício Pires de Moura do Amaral 3 , Daniel Dias Rufino Arcanjo 3 , Hercília Maria Lins Rolim 1
Affiliation  

In the search for anxiolytic drugs with fewer adverse effects, calcium blockers were proposed as a benzodiazepines (BZDs) alternative. In this context, the anxiolytic effect of nimodipine has been demonstrated. However, its low bioavailability and solubility could be improved by using nanostructured drug delivery systems such as liposomes. In this way, liposomal formulation containing nimodipine (NMD-Lipo) was developed. The NMD-lipo is a formulation capable of improving the kinetic characteristics of the drug, as well as the anxiolytic effect of nimodipine. In this work, the serotonergic system participation in the anxiolytic mechanism of the liposomal formulation containing nimodipine (NMD-Lipo) was investigated. A possible 5-HT1A receptor mediation on the NMD-Lipo anxiolytic effect was demonstrated by using WAY 100635 (5-HT1A receptor antagonist) since the antagonist reversed the NMD-Lipo anxiolytic effect in the light/dark test and elevated plus maze test. The results demonstrated that the NMD-Lipo administration had anxiolytic activity through 5-HT1A receptors without causing sedation or compromising the motor coordination of the tested animals.



中文翻译:

含有尼莫地平的脂质体制剂(NMD-Lipo)的抗焦虑作用机制中血清素能系统的参与

在寻找副作用较少的抗焦虑药物时,钙阻滞剂被提议作为苯二氮卓类(BZD) 的替代品。在这种情况下,尼莫地平的抗焦虑作用已得到证实。然而,其低生物利用度和溶解度可以通过使用纳米结构药物递送系统(例如脂质体)。这样,含有尼莫地平的脂质体制剂(NMD-Lipo)被开发出来。NMD-lipo 是一种能够改善药物动力学特性以及尼莫地平的抗焦虑作用的制剂。在这项工作中,研究了血清素能系统参与含有尼莫地平(NMD-Lipo)的脂质体制剂的抗焦虑机制。使用 WAY 100635(5-HT1A 受体拮抗剂)证明了 5-HT1A 受体可能介导 NMD-Lipo 抗焦虑作用,因为该拮抗剂在明/暗测试和高架十字迷宫测试中逆转了 NMD-Lipo 抗焦虑作用。结果表明,NMD-Lipo 给药通过 5-HT1A 受体具有抗焦虑活性,不会引起镇静或损害测试动物的运动协调性。

更新日期:2023-10-09
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