大脑alpha7烟碱受体可能是一个重要的治疗目标治疗阿尔茨海默氏症:研究DMXBA (GTS-21)。

文章的细节

引用

复制到剪贴板

克姆福

大脑alpha7烟碱受体可能是一个重要的治疗目标治疗阿尔茨海默氏症:研究DMXBA (GTS-21)。

Behav大脑研究》2000年8月,113 (2):169 - 81。

PubMed ID

10942043 (在PubMed

]

文摘

大大脑烟碱受体水平下降发生在阿尔茨海默病,相对于毒蕈碱的和其他受体。神经元具有高亲和力烟碱受体似乎特别脆弱。低亲和力烟碱受体的选择性结合alpha-bungarotoxin没有显著影响。主要的烟碱受体亚型结合这个毒素是一种homo-oligomer alpha7子单元组成。由于其极高的钙离子选择性,这种特殊的受体可以被视为一种ligand-gated钙通道。Alpha7受体中发现的大脑区域是重要的认知,包括大脑皮层和海马。海马受体大多局限于gaba ergic中间神经元。Alpha7受体似乎不太可能比alpha4-beta2受体上调数量和抑制在函数由于慢性受体激动剂接触。一家基于海洋动物毒素anabaseine烟碱受体激动剂合成和调查。这些化合物之一,DMXBA [3 - (2, 4-dimethoxybenzylidene) -anabaseine; code name GTS-21] has displayed promising characteristics during phase I clinical tests. In the rat DMXBA is selectively agonistic upon alpha7 nicotinic receptors. In addition it is a moderately potent antagonist at alpha4-beta2 receptors. DMXBA enhances a variety of cognitive behaviors in mice, monkeys, rats and rabbits. It also displays neuroprotective activity upon cultured neuronal cells exposed to beta-amyloid or deprived of NGF. The compound is much less toxic than nicotine and does not affect autonomic and skeletal muscle systems at doses which enhance cognitive behavior. Phase I clinical tests indicate that large doses can be safely administered orally without adverse effects. Psychological tests on healthy young male subjects indicate a positive effect of DMXBA on some measures of cognition. While DMXBA is a much weaker partial agonist on human alpha7 receptors than upon rat alpha7 receptors, its 4-hydroxy metabolite has been shown to have excellent efficacy on both receptors. Thus, some of the physiological and behavioral effects of GTS-21 may be due to the actions of this primary metabolite.

beplay体育安全吗DrugBank数据引用了这篇文章

药物

GTS-21