On September 14, Nature Neuroscience published the research results of Chen Yelin, a researcher of the Chinese Academy of Sciences Shanghai Institute of Organic Chemistry, on new antidepressant drugs. This study, which has been conducted for 6 years and submitted for over two years, discovered the mechanism of action of the antidepressant drug, Esketamine. The reviewer evaluated this as a "particularly thorough study", and based on the relevant targets and mechanisms of action, researchers have the potential to develop a "perfect drug" that can quickly combat depression with lower side effects. According to statistics from the World Health Organization, depression affects more than 300 million people worldwide, but there is currently a lack of effective treatment drugs. At present, the treatment of depression is mainly represented by psychoactive drugs such as Prozac. But such drugs have slow effects and usually need to be taken continuously for more than 3 weeks to determine whether they are effective. If they do not work, it is necessary to try increasing the dosage. One third of patients, no matter how much they increase their dosage or try other antidepressants, are not effective, and the cost of trial and error is high. "Chen Yelin said," Treating depression usually takes more than half a year, and patients who hastily stop taking drugs will have a withdrawal reaction. More importantly, such drugs cannot alleviate suicidal tendencies, and patients with suicidal tendencies should not take them, A rapid antidepressant drug Spravato (Esketamine) nasal spray approved by the National Drug Administration has been launched. This is the first antidepressant drug approved in China with a novel mechanism of action, which can quickly alleviate the symptoms of patients with acute suicidal ideation or behavior. In fact, ketamine has been used as an anesthetic and analgesic in the medical system for decades, "said co author Su Tonghui. Ketamine is composed of two chiral symmetric molecules, left and right, mixed in a 1:1 ratio, and Esketamine is one of the components - right ketamine. In 2004, scientists accidentally discovered that Esketamine has a rapid antidepressant effect, which can alleviate depressive symptoms within two to three hours. It is also effective for patients with refractory depression and can alleviate suicidal tendencies. In 2019, Esketamine was approved for listing in the United States. Although the drug has excellent rapid antidepressant activity, it has hallucinogenic effects and a certain degree of addiction. This has led to the drug being classified as a controlled drug and must be used under the supervision of a doctor at a designated clinic. Patients usually have to stay in the hospital for two to three hours, waiting for their hallucinations to disappear before leaving, causing great inconvenience in medication. Esketamine is a new drug mechanism of action, but people are not clear about what this mechanism is. "Co author Lu Yi of the paper said," Because this drug was accidentally discovered to have antidepressant effects and people were not clear about its mechanism of action, it was not optimized, and the side effects were very obvious. "Taking a difficult path is how to further develop fast antidepressant drugs with smaller side effects based on the mechanism of Esketamine, Becoming the focus of attention in this field. However, there are two key issues that have been troubling the development of such drugs: firstly, the target of action of Esketamine is unclear; The second question is whether the side effects of Esketamine are related to the mechanism of antidepressant activity, and whether the two can be separated. Prior to the launch of Esketamine in the United States, the academic community had already begun to discuss