The selective nicotinic acetylcholine receptor α7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain
The selective nicotinic acetylcholine receptor α7 agonist JN403 is active in animal models of cognition, sensory gating, epilepsy and pain
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DOI：
10.1016/j.neuropharm.2008.08.025
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发表时间：
2009-01-01
影响因子：
4.7
通讯作者：
Hoyer, Daniel
中科院分区：
文献类型：
--
作者：
Feuerbach, Dominik;Lingenhoehl, Kurt;Hoyer, Daniel
一些证据表明，烟碱型乙酰胆碱受体α7(nAChRα7)与精神分裂症和阿尔茨海默病等中枢神经系统疾病以及败血症和胰腺炎等炎症性疾病有关。本文描述了JN403的体内效应，JN403是一种最近被鉴定为有效和选择性的部分nAChRα7激动剂的化合物。JN403静脉注射后迅速渗透到脑内。在邮局之后。小鼠和大鼠给药。在小鼠的社会识别测试中，JN403在广泛的剂量范围内促进了学习/记忆能力。JN403在大鼠社会探索模型中表现出类焦虑作用，其作用在给药前6h和亚慢性给药后仍保持不变。在DBA/2小鼠身上研究了其对感觉抑制的影响，DBA/2是一种在标准实验条件下感觉抑制减少的品系。全身应用JN403可恢复DBA/2小鼠的感觉门控。在麻醉和清醒的动物中都是如此。此外，JN403在DBA/2小鼠的听源性癫痫发作范式中显示出抗惊厥的潜力。在测试的两种永久性疼痛模型中，JN403可显著逆转机械性痛觉过敏。这组数据表明，nAChRα7激动剂，如JN403，可能有助于改善学习/记忆成绩，恢复感觉门控缺陷，减轻疼痛、癫痫发作和焦虑状态。(C)2008爱思唯尔有限公司。保留所有权利。
Several lines of evidence suggest that the nicotinic acetylcholine receptor alpha 7 (nAChR alpha 7) is involved in central nervous system disorders like schizophrenia and Alzheimer's disease as well as in inflammatory disorders like sepsis and pancreatitis. The present article describes the in vivo effects of JN403, a compound recently characterized to be a potent and selective partial nAChR alpha 7 agonist. JN403 rapidly penetrates into the brain after i.v.. and after p.o. administration in mice and rats. In the social recognition test in mice JN403 facilitates learning/memory performance over a broad dose range. JN403 shows anxiolytic-like properties in the social exploration model in rats and the effects are retained after a 6 h pre-treatment period and after subchronic administration. The effect on sensory inhibition was investigated in DBA/2 mice, a strain with reduced sensory inhibition under standard experimental conditions. Systemic administration of JN403 restores sensory gating in DBA/2 mice. both in anaesthetized and awake animals. Furthermore, JN403 shows anticonvulsant potential in the audiogenic seizure paradigm in DBA/2 mice. In the two models of permanent pain tested, JN403 produces a significant reversal of mechanical hyperalgesia. The onset was fast and the duration lasted for about 6 h. Altogether, the present set of data suggests that nAChR alpha 7 agonists, like JN403 may be beneficial for improving learning/memory performance, restoring sensory gating deficits, and alleviating pain, epileptic seizures and conditions of anxiety. (C) 2008 Elsevier Ltd. All rights reserved.