Neuron: breakthrough! Scientists are expected to develop new antidepressants

December 2, 2019 / Biovalley bio on / - recently, in a research report published in the international journal Neuron, scientists from Vanderbilt University Medical Center made great progress in the development of antidepressants The relevant research results may be expected to develop new antidepressants with quick effect, more effective symptom relief and less side effects Photo source: neuron researchers' approach can increase the supply of glutamate, an excitatory neurotransmitter in a specific part of the brain, which may regulate the body's mood by reducing the activity of receptors that inhibit glutamate release Using drug like molecules to selectively inhibit the receptors mglu2 and mglu3 may block the long-term changes of glutamate in animals, said Max Joffe, a researcher The glutamate receptors (mglu2 and mglu3) are located on opposite sides of the synapse or in the gap between nerve cells Researchers said that depression is not a single disorder With the deepening of research, they gradually found that mglu2 and mglu3 play an important role in different aspects of depression, and different patients have different responses to the two receptors Special compounds can affect the neural circuit between the prefrontal cortex and thalamus Because the circuit is involved in the body's attention and cognitive function, it is also very important for rapid antidepressant SSRIs, the most common antidepressant, can selectively inhibit serotonin reuptake, but it takes weeks to release symptoms Anxiety is a common side effect, and one third of patients have no response to antidepressants Ketamine was first used as an anesthetic Recently, researchers have used it to quickly help patients release symptoms of depression The drug can potentially play a role by releasing glutamate "burst", but the treatment must be strictly monitored, because the drug can induce hallucinations and other psychiatric symptoms Another way to get the brain out of depression is to increase glutamate levels in the prefrontal cortex by reducing the activity of specific glutamate receptors Metabotropic glutamate receptors play a key role in the process of cognition, memory and movement, as well as in the occurrence of many diseases (schizophrenia, etc.) Metabotropic receptors are membrane receptors that act through a second messenger Over the years, researchers have developed a series of compounds called "allosteric regulators", which can act as dimmer switches in circuits, slow or increase glutamate transport in special brain circuits without inducing side effects Researchers have found that slowing down the activity of mglu2 and mglu3 can enhance the transmission of signals in the hypothalamic cortex, and inhibit the long-term depression performance of patients Now researchers have begun to understand the difference between the two receptors through more in-depth research, and how they are uniquely related to specific patient groups with different depression symptoms Original sources: Max E Joffe, Chiaki I Santiago, Kendra h Oliver, et al Mglu2 and mglu3 negative allosteric modulators divergently enhance thalamocortical transmission and exercise rapid antipressant like effects, neuron (2019) Doi: 10.1016/j.neuron.2019.09.044