异缬氨酸:一种独特的氨基酸,具有抗癫痫药物的特性

W. Yu, Damian S Shin
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摘要

目前的抗癫痫药物主要通过减少神经网络的兴奋或增加神经网络的抑制来起作用。这是通过使Na +或ca2 +离子通道失活并减少谷氨酸释放或通过增强gaba能影响来实现的。尽管使用了这些抗癫痫药,大约30%的癫痫患者仍然难治性。因此,显然有必要开发新的aed,通过新的机制来提供更大的疗效。考虑到这一点,我们研究了异缬氨酸,一种与甘氨酸和GABA具有相似化学结构的独特氨基酸,是否可以填补这一角色。先前,我们发现异缬氨酸通过一种新机制在体外减轻了癫痫样事件(SLEs)。在本研究重点中,我们讨论了我们最新发表的研究结果,这些发现证明了异缬氨酸在体内大鼠癫痫模型中的功效。
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Isovaline: A unique amino acid with antiepileptic drug properties
Current anti-epileptic drugs (AEDs) primarily act by decreasing excitation or increasing inhibition of the neuronal network.  This is achieved by inactivating Na + or Ca 2+ ion channels and decreasing glutamate release or by enhancing GABAergic influence.  Despite using these AEDs, approximately 30% of epileptic patients remain intractable.  As a consequence, there is a clear need to develop new AEDs that may work via novel mechanisms to provide greater efficacy.  With this in mind, we investigated whether isovaline, a unique amino acid with a similar chemical structure to glycine and GABA, could fill this role.  Previously, we showed that isovaline attenuated seizure-like events (SLEs) in vitro via a novel mechanism.  In this research highlight, we discuss our latest published findings which demonstrate the efficacy of isovaline in an in vivo rat model of epilepsy.
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