Inasmuch as glutamate is the main excitatory neurotransmitter in the central nervous system, strategies aimed at counteracting glutamate excitotoxicity, which is at least partially involved in many acute neurologic, chronic neurodegenerative and psychiatric diseases, are challenging. Blockade of the NMDA receptor was identified as one way of achieving selective antagonism and overcoming glutamate neurotoxicity, yet not without liabilities. Glycine site antagonism of the NMDA receptor in 1987 offered a significant advance in blocking this receptor because such drugs were shown to lack most of the side effects, such as memory impairment, ataxia, lack of motor coordination and psychotomimetic effects, which accompanied competitive and non-competitive NMDA receptor antagonists. To date, much has been done to improve the structure-activity relationship (SAR) of compounds resulting in the synthesis of ACEA 1021. It is unclear, however, whether further chemical substitutions will lead to an improved compound.Many studies have been performed with ACEA 1021 and although there are much in vitro and in vivo data to support its neuroprotective effects and improved safety profile, there is very little published information regarding its clinical pharmacology. In order to properly evaluate the true potential for ACEA 1021 in acute and chronic CNS disorders additional longer term safety and efficacy data in humans are needed.
展开▼
机译：由于谷氨酸是中枢神经系统中主要的兴奋性神经递质，因此旨在抵消谷氨酸兴奋性毒性的策略具有挑战性，而谷氨酸兴奋性毒性至少部分涉及许多急性神经系统疾病，慢性神经变性疾病和精神疾病。 NMDA受体的阻滞被认为是实现选择性拮抗和克服谷氨酸神经毒性的一种方法，但并非没有责任。 1987年，NMDA受体的甘氨酸位点拮抗作用在阻断该受体方面取得了重大进展，因为这种药物被证明缺乏大多数副作用，例如记忆力减退，共济失调，缺乏运动协调性和拟精神病作用，并伴有竞争性和非竞争性。 -竞争性NMDA受体拮抗剂。迄今为止，已经做了很多工作来改善化合物的结构-活性关系（SAR），从而合成ACEA1021。但是，尚不清楚是否进一步的化学取代会导致化合物的改进。 ACEA 1021，尽管有大量体外和体内数据支持其神经保护作用和改善的安全性，但有关其临床药理学的已发表信息很少。为了正确评估ACEA 1021在急性和慢性中枢神经系统疾病中的真正潜力，还需要其他长期的人类安全性和有效性数据。
展开▼
