Recently, the Center of Molecular Cell Excellence of the Chinese Academy of Sciences cooperated with ShanghaiTech University to complete the design of a new rapid antidepressant compound oriented to the structure of hallucinogens and their targets, which pointed out the direction for the research and development of a new generation of non-hallucinogenic and rapidly effective antidepressants. The results were published in the international academic journal Science on January 28.
According to statistics, there are about 322 million people with depression worldwide, and the traditional antidepressants currently on the market usually take up to weeks or even months to take effect, and have no improvement effect on one-third of patients with refractory depression. In recent years, multiple hallucinogens have shown some potential in the treatment of depression. Scientists extracted a class of natural hallucinogens from the "magic mushroom" - psilocybin, and the results of the second phase of clinical studies showed that psilocybin can greatly improve the symptoms of depressed patients in one day, and the effect can last for more than three months. However, the hallucinogenic side effects of hallucinogens greatly limit their clinical research and widespread application. Therefore, scientists around the world have been working to find and develop new antidepressants that are non-hallucinogenic and can work quickly.
Psilocybin is metabolized in the human body to dephosphate psilocybin, which further binds to serotonin 2A receptors and works. Through structural analysis, the researchers found that psilocybin dephosphate has another lipid-regulated binding pattern in addition to the previously predicted classical binding pattern with serotonin 2A receptors.
Based on the second binding mode, the researchers designed and synthesized a series of preferred agonists represented by IHCH-7086 and IHCH-7079 for the signaling of serotonin 2A receptor β-arrestin, and experimentally verified in animals that the compounds had no hallucinogenic effect and had rapid antidepressant effects. The research results point the way for the development of a new generation of non-hallucinogenic antidepressants that act quickly. According to researchers, compounds are not equivalent to drugs, and a large number of experimental verifications are needed to be carried out to make them drugs that benefit patients as soon as possible.
(CCTV reporter Shuai Junquan)
Source: CCTV news client