The first three generations of antidepressants have a disadvantage, that is, delayed onset. The uncoupling lead compound ZZL-7 developed by Zhou Qigang's team can take effect quickly, which may overcome the defect that the third-generation antidepressants rely on 5-HT self receptor desensitization, and develop into a new generation of fast antidepressants. Anorexia, depression, insomnia, fidgety, restlessness... In the Complete Works of Hippocrates, Hippocrates, the founder of western medicine, called the disease with this group of symptoms depression. Depression, even in today's highly developed modern medicine, is still known as "the biggest killer in the 21st century". According to the World Health Organization, 280 million people worldwide suffer from depression. Recently, the joint research team of the State Key Laboratory of Reproductive Medicine of Nanjing Medical University and the School of Pharmacy, Professor Zhou Qigang, Professor Zhu Dongya and Professor Li Tingyou, discovered a new strategy for the treatment of depression and synthesized a candidate antidepressant lead compound that can take effect quickly. Relevant research papers were published in Science. The first two generations of antidepressants have side effects. "The occurrence of depression is related to genetic, social, psychological, environmental, biochemical and other factors. It is a clinical syndrome, and its etiology is not completely clear. For a long time, human beings have not found a specific drug to treat depression until the 1950s." Zhou Qigang, the corresponding author of the paper, told the Science and Technology Daily. The discovery of antidepressants was an accident. Zhou Qigang introduced that at first, doctors found that the mood, appetite and happiness of patients were significantly improved after taking isoniazid (hereinafter referred to as isopropyl hydrazine) to treat tuberculosis. The drugs that inhibit the action of monoamine oxidase, represented by isopropyl hydrazine, were later regarded as the first generation of antidepressants. The discovery of isopropyl hydrazine inspired scientists to develop antidepressant drugs. Soon, imipramine, the representative of the second generation of antidepressants, was screened out. This kind of medicine was then used to treat schizophrenia. The first two generations of antidepressants that were unintentionally targeted at 5-hydroxytryptamine (5-HT). "5-HT can regulate our cognitive function, especially emotion and emotion. The decrease of 5-HT content in the synaptic space will make us feel anxious, depressed, and even suffer from depression. Although the first generation antidepressant drugs can inhibit the activity of monoamine oxidase and increase the content of 5-HT in the synaptic space. However, monoamine oxidase is abundant in the body, and inhibiting its activity will lead to serious side effects, such as monoamine oxidase also exists in the liver , if it is inhibited, there will be hepatotoxicity. " Zhou Qigang said, "At present, the first generation antidepressant isopropyl hydrazine has basically been withdrawn from the market and is no longer used." Studies on the second generation of antidepressants found that these drugs also increase the concentration of 5-HT and norepinephrine by inhibiting the reabsorption of 5-HT and norepinephrine in the synaptic space by the 5-HT transporter (SERT) and norepinephrine transporter (NET), thus playing an antidepressant role, but they also have many side effects. "Based on a series of discoveries, in the 1960s, scientists put forward the classic depression monoamine hypothesis