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Application of GABAB receptor antagonist in aspect of blocking TREK-1 channel

A technology of receptor antagonists and channels, applied in the application field of GABAB receptor antagonists in blocking TREK-1 channels, can solve the problems of inability to achieve antidepressant treatment, increase the complexity of the onset of depression, the complexity of pathogenesis, etc. question

Inactive Publication Date: 2019-01-04
THE SECOND HOSPITAL OF DALIAN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the pathogenesis of depression is closely related to heredity, neuroendocrine, imbalance of inhibition and excitation, oxidative stress, apoptosis of neurons, neurodegenerative changes and environmental factors, and the comorbidity of anxiety and depression has greatly increased. The complexity of the onset of depression
Therefore, the complexity and ambiguity of the pathogenesis of depression make the efficacy of antidepressant drugs based on a single mechanism model far from meeting the expectations of antidepressant treatment in modern society

Method used

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  • Application of GABAB receptor antagonist in aspect of blocking TREK-1 channel
  • Application of GABAB receptor antagonist in aspect of blocking TREK-1 channel
  • Application of GABAB receptor antagonist in aspect of blocking TREK-1 channel

Examples

Experimental program
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preparation example Construction

[0141] 3 Preparation of chronic stress-stimulated depression model

[0142] According to Katz and Willner’s improved method, a chronic unpredictable stress (CUS) model was prepared with chronic unpredictable stress. All rats were kept in cages with a diurnal cycle, with 8 rats per cage, and the rats were given freedom before the experiment. Diet, adapt to the environment for a week. The breeding environment is suitable, temperature: 22±1°C, humidity 55%-60%. After the environmental adaptation, the model group gave rats a stimulus every day for 27 days, and each stimulus would not appear continuously within two days. The stimulus types included: 30 minutes of restraint, 24 hours of fasting, 24 hours of water deprivation, and 15 minutes of warm water swimming (31°C), 10 minutes of cold water swimming (18°C), 24 hours of single-cage feeding, 24 hours of moist bedding with a 30° inclined cage, 10 minutes of mouse tail clipping (1 cm from the root of the tail) and overnight lighti...

Embodiment 1

[0144] Behavioral testing - open field test (OFT)

[0145]The open field test, also known as the open box test, is a method to evaluate the autonomous behavior, exploratory behavior and tension of experimental animals in a novel environment. The inner wall of the rat open field test box (90cm×90cm×40cm) is black, and the bottom surface is divided into 9 small squares (30cm×30cm) on average. In the animal behavior analysis system, the open field test box starts from the upper left and presses left to Right, top to bottom are numbered sequentially, of which 5 is the central area, and the rest are peripheral areas. A digital camera is set up 1 meter above, and its field of view can cover the entire open field. The open field lighting is fully artificial lighting (about 40LX) to avoid light interference. The experiment was carried out in a quiet environment. Experimenters and computers and other equipment were placed in another room to reduce interference with animal behavior. T...

Embodiment 2

[0150] Behavioral testing - sucrose preference test (SPT)

[0151] The sugar water preference test is a behavioral experimental method used to evaluate the degree of anhedonia in rats. Since anhedonia can best reflect the core symptoms of depression, this experiment can reflect the degree of depression in rats to a greater extent. Referring to relevant literature, rats need to be trained to learn and adapt to drinking sucrose water before the formal start of the experiment. Two bottles of 1% sucrose water should be placed in each cage, and the rats should try to drink sucrose water for 24 hours first; then in the second 24 hours, each cage should be replaced with a bottle of pure water and a bottle of 1% sucrose water for normal rats. Among them, the left and right positions of two water bottles need to be replaced in 12 hours; in the last third 24 hours, two bottles of normal rats are placed in each cage to drink pure water. After the sucrose water acclimatization, there wa...

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Abstract

The invention belongs to the technical field of biological medicines, and particularly relates to an application of a GABAB receptor antagonist in an aspect of blocking a TREK-1 channel. It is indicated from research in an embodiment of the application that the GABAB receptor antagonist acts on the TREK-1 channel and has the anti-depression effect, it has important theoretical significance and anapplication value to reveal a pathogenesis of depression and guide clinical compatibility of drugs. So, the GABAB receptor antagonist has good application prospect in aspects of preparing an antidepressant drug and a biliary tract obstruction drug, and preparing drugs for treating TREK-1 channel related diseases.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, in particular to GABA B Use of receptor antagonists in blocking TREK-1 channels. Background technique [0002] Depression, also known as depressive disorder, is characterized by low emotion, slow thinking, and decreased speech and movement. Depression has seriously plagued the life and work of patients, and brought a heavy burden to families and society. Studies have shown that about 15% of patients with depression die by suicide, accounting for two-thirds of the total suicide population. According to the World Health Organization, there are 350 million patients with depression in the world, and nearly 100 million in my country. Depression has become the fourth largest disease in the world. According to WHO's global medical burden of disease, depression will become the second largest psychosomatic disorder in the world in the next ten years. So far, the etiology of depression is not clear,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/662A61P25/28
CPCA61K31/662A61P25/28A61K2300/00
Inventor 肖昭扬殷盛明徐红王冬梅赵杰李韶孙艺平于德钦李怀锐余伟志薛莹
Owner THE SECOND HOSPITAL OF DALIAN MEDICAL UNIV
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