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从巴西游走蛛(蜘蛛目,园蛛科)毒液中纯化得到的Parawixin-11在Wistar大鼠中的抗癫痫特性

Antiepileptic profile of Parawixin-11, purified from Parawixia bistriata spider venom (Araneae, Araneidae), in Wistar rats.

作者信息

Pereira Adriana Colsera, Cunha Alexandra Olimpio Siqueira, Mortari Márcia Renata, Fachim Helene Aparecida, Campos Gabriel Avohay Alves, Lopes Norberto Peporine, Dos Santos Wagner Ferreira

机构信息

Neurobiology and Venoms Laboratory, Department of Biology, College of Philosophy, Sciences and Literature (FFCLRP), University of São Paulo (USP), Av. Bandeirantes, 3900, Ribeirão Preto, São Paulo, CEP: 14040-090, Brazil.

Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, São Paulo, Brazil.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan;398(1):629-639. doi: 10.1007/s00210-024-03299-x. Epub 2024 Jul 23.

Abstract

The pharmacological treatment of epilepsy is often complex due to the lack of efficacy in many patients and profound side effects from current drugs, including sedation, motor impairment, and teratogenesis. In the quest for new antiepileptic drugs, animal venoms offer a valuable source of neuroactive molecules targeting ion channels and neurotransmitter receptors. This study investigates the antiepileptic potential of compounds isolated from the venom of the Parawixia bistriata spider. One compound, designated Parawixin-11, demonstrated significant anticonvulsant effects when injected into the cerebral ventricle in a dose-response manner. It effectively countered seizures induced by bicuculline (ED50 0.16 µg/animal), pentylenetetrazole (ED50 0.08 µg/animal), strychnine (ED50 0.05 µg/animal), pilocarpine (ED50 0.10 µg/animal), and NMDA (ED50 0.008 µg/animal). We also assessed whether intracerebroventricular administration of Parawixin-11 caused motor or cognitive impairments in rats using the open field, rotarod, and Morris water maze tests. No differences in exploration or movement were observed with doses of 0.3, 0.2, or 0.1 µg of Parawixin-11. Although there was an increased latency to find the platform during the acquisition phase of the Morris water maze test, no differences in spatial memory retention were noted. Given Parawixin-11's potency against NMDA-induced seizures, we hypothesize that it may modulate the glutamatergic system, aligning with the mechanisms of several spider-derived polyamines.

摘要

由于许多患者药物疗效不佳以及现有药物存在严重副作用,包括镇静、运动障碍和致畸作用,癫痫的药物治疗往往很复杂。在寻找新型抗癫痫药物的过程中,动物毒液提供了针对离子通道和神经递质受体的有价值的神经活性分子来源。本研究调查了从双带舞蛛毒液中分离出的化合物的抗癫痫潜力。一种名为Parawixin - 11的化合物,以剂量反应方式注入脑室时显示出显著的抗惊厥作用。它能有效对抗荷包牡丹碱(半数有效剂量为0.16微克/只动物)、戊四氮(半数有效剂量为0.08微克/只动物)、士的宁(半数有效剂量为0.05微克/只动物)、毛果芸香碱(半数有效剂量为0.10微克/只动物)和N - 甲基 - D - 天冬氨酸(半数有效剂量为0.008微克/只动物)诱发的癫痫发作。我们还使用旷场试验、转棒试验和莫里斯水迷宫试验评估了脑室内注射Parawixin - 11是否会导致大鼠出现运动或认知障碍。在注射0.3、0.2或0.1微克Parawixin - 11时,未观察到探索或运动方面的差异。尽管在莫里斯水迷宫试验的获取阶段找到平台的潜伏期有所延长,但在空间记忆保持方面未发现差异。鉴于Parawixin - 11对N - 甲基 - D - 天冬氨酸诱发癫痫发作的效力,我们推测它可能调节谷氨酸能系统,这与几种蜘蛛衍生的多胺的作用机制一致。

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