< span lang =“en - us”> S-ketamine的抗抑郁作用一直是最有前途的成功之一< a href = " //www.qianliexian123.com/drug discovery/news/antidepressant - - - - - - -基于氯胺酮- -支持来自fda咨询-组织- 315379”目标= "平等" > < / >的故事从迷幻药物的研究。外消旋氯胺酮,低剂量的镇定剂导致幻觉,是一种平等的两个手性分子,S-ketamine R-ketamine。这些都是镜面反射,被称为对映体,否则是相同的。虽然S-ketamine现在已经成为抗抑郁鼻喷剂Spravato许可,研究其镜像分子更加有限。< / span > < / p > < p class = "身体" > < span lang =“en - us”> < br > < / span > < / p > < p class = "身体" > < div class = " flex flex-column flex-align-items-center image-modal ' > < img类=“img-responsive center-block“alt = " src = " https://cdn.technologynetworks.com/tn/images/body/randsketamien1617978190073.jpg " > < / div > < / p > < p class = "身体" > <我> r -和s-ketamine分子对映体手性分子的镜像彼此只< / i > < / p > < p class = "身体" > < span lang =“en - us”> < br > < / span > < br >现在,药物开发者说R-ketamine可能会提供一个更有针对性的行动更少的副作用比双胞胎更受欢迎。了解更多,我们采访了特伦斯凯利,总裁兼首席执行官在认知神经科学,atai生命科学的平台公司。感觉最近宣布了一项与大冢制药公司合作开发R-ketamine-based疗法。< br > < br > < b > Ruairi Mackenzie (RM): R-ketamine如何不同于S-ketamine在生物层面上吗?< br > < br >特伦斯凯利(TK) < / b >:其中一些已知和未知的仍然是只所谓R-ketamine是一个较弱的NMDA受体拮抗剂在显然是与一些拟精神病的副作用和麻醉特性rac-ketamine和S-ketamine又是;在此基础上,我们希望R-ketamine的副作用会更有利的只不知道是如何抗抑郁作用的机制不同,但似乎从发表的临床研究,可能会有不同的化合物是如何工作又是; Studies in rodents are starting to pinpoint different biological pathways for the R- and S-derivatives and Perception is intending to use some of the recent upfront payment from our licensing deal to support this work.

RM: Why has S-ketamine been the dominant compound tested in clinical trials up until now?

TK: Probably for two reasons:  the first is that the initial hypothesis that the activity at the NMDA receptor was driving the anti-depressive effect.  If you believe this hypothesis, then pursuing the more potent enantiomer would make sense.  The problem is that this mechanism also drives the psychotomimetic side effects.  The second reason is likely because S-ketamine was approved as an anesthetic in Europe.  This meant that there was already a large data set on the drug and a clear regulatory history. 

RM: What is the current evidence base around R-ketamine’s antidepressant action? 

TK: There is much data based on rodent models of depressive-like behaviors.  In these models, R-ketamine often appears to be more potent, longer lasting and with a potential lower abuse liability.  On the human side, the best evidence, to date, comes from a small, open-label study in depression published by Lucas Quarantini’s group in Brazil in 2020 that may suggest an antidepressant effect in 7 patients with minimum dissociation.

RM: Ketamine-based antidepressants are thought to be able to mediate effects in a far shorter time than traditional SSRIs. Will those effects also be quicker to wear off?

TK: Rapid onset of effect is one of the key benefits that we hope to be able to demonstrate with R-ketamine.  Based on the rodent models that were discussed above, there are good indications that the effect could have a rapid onset and be at least as durable as S-ketamine.  The rapid onset of effect was also supported by the data from 7 patients published by Quarantini. Regarding the durability of R-ketamine and SSRIs, data is required to demonstrate difference, however Perception Neuroscience’s current focus is on progressing PCN-101 (R-ketamine) to a Phase 2 proof-of-concept trial in patients with Treatment Resistant Depression.

Terence Kelly was speaking to Ruairi J Mackenzie, Senior Science Writer for Technology Networks

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