According to WHO data, 280 million people worldwide suffer from depression. In just the past three years, more than 70 million new patients with depression in have been added worldwide. Depression , known as the "big killer of the 21st century".
The existing antidepressant drugs take 2 to 4 weeks before the patient starts to show efficacy, which is not conducive to the treatment of severe patients in the acute attack stage. Moreover, this type of drug is only effective for some patients and its efficacy is unstable. It may not only be ineffective for some patients, but may even aggravate the patient's symptoms.
How to overcome the shortcomings of existing antidepressants? Recently, Professor Zhou Qigang, Professor Zhu Dongya, Professor Li Tingyou , the National Key Laboratory of Reproductive Medicine of Nanjing Medical University, and Professor Zhou Qigang, Professor Zhu Dongya, and Professor Li Tingyou , jointly discovered a new target that can develop rapid antidepressant drugs, and synthesized a candidate antidepressant pilot compound that can take effect quickly, which can overcome multiple side effects of existing antidepressants and is expected to become a candidate drug for a new generation of antidepressants. Research results related to have been published in the international academic journal Science.
Currently recognized by the academic community as the main pathogenic mechanism of depression is the reduction of serotonin neurotransmitters in the synaptic cleft of neurons in the brain. As one of the types of neurotransmitters, 5-hydroxytryptamine mainly mediates depression in humans, and increasing the serotonin concentration in the synaptic cleft can exert an antidepressant effect. This is the "monoamine hypothesis" that has been used for nearly 60 years.
research team introduced: "Since the discovery of antidepressants in the 1950s, the first and second generation antidepressants have had many and serious side effects. The third generation antidepressants based on the theoretical basis of the 'monoamine hypothesis' was launched in the 1980s and are still used in the clinical frontline." For example, the classic antidepressant fluoxetine - is the well-known Prozac, which was developed based on the "monoamine hypothesis".
"But the brain is magical. There is also a very specific nucleus at brain stem . A large amount of serotonin is synthesized here and then emitted to the whole brain through neurons." Professor Zhou Qigang explained, "The brain has a negative feedback mechanism. The role of serotonin transporter inhibitors at synapses and brain stems is completely opposite. In the early stage of the use of serotonin transporter inhibitors, the balance effect of the two aspects has led to the inability to exert antidepressant efficacy. It is necessary to wait until the serotonin self-receptor of the dorsal nucleus is desensitized before fluoxetine and other drugs can show antidepressant effects."
This is why, after patients with depression take the medicine, they still have the situation described in the beginning of the article: is slow to take effect, and a very small number of people will aggravate the condition and even induce suicide after taking it. After years of research, the
team discovered a new antidepressant target, namely the coupling target of the serotonin transporter located in the dorsal nuclear region of the mid-slit and neuronal nitric oxide synthase . Unlocking the SERT-nNOS coupling can desensitize without dependent on serotonin autoreceptors and exert rapid antidepressant effects. Based on this, the research team synthesized a rapidly acting antidepressant pilot compound "ZZL-7". Mice experiments showed that "ZZL-7" had an antidepressant effect 2 hours after injection. The new discovery of
not only elucidates the fundamental reason for the delayed onset of drugs based on the "monoamine hypothesis", but also achieves short-term rapid onset through new targets, and in the theoretical sense, it can completely overcome the possibility of previous drug side reaction defects. The international academic community believes that this research results rewritten the traditional understanding that monoamine antidepressants can only take effect slowly, and are a major theoretical breakthrough in the field of antidepressants research in the "monoamine hypothesis" proposed in the past 60 years and the third-generation antidepressants were launched in the nearly 40 years.
"We have a lot to do. It often takes 10-15 years for to go from the discovery of targets to the launch of real drugs ." Professor Zhou Qigang said, "In the future, we will use ZZL-7 as the parent core structure to further study and screen out compounds with higher activity and good drug properties, and strive to develop a new generation of antidepressants."
Source: Guangming Daily
Process Editor: TF016
