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Application of P2Y1 receptor and blocking agent of P2Y1 receptor in prevention and treatment of anti-depression symptom and/or anti-anxiety symptom

A P2Y1, antidepressant technology, applied in the field of biopharmaceutical medicine, can solve the problems of slow onset of antidepressant drugs, low drug efficacy, insensitivity, etc., and achieve good application prospects and research value.

Active Publication Date: 2018-01-19
SOUTHERN MEDICAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The existing treatment of depression mainly relies on drug therapy, but it still faces many severe challenges: first, the drug efficacy is low, and about 35% of patients are not sensitive to the existing antidepressant drugs; secondly, the drug compliance is poor, and the existing antidepressants Antidepressant drugs take effect slowly and take at least 3 to 6 weeks to take effect, and many patients will give up halfway; third, the side effects of drugs are large and there is a high recurrence rate after drug withdrawal

Method used

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  • Application of P2Y1 receptor and blocking agent of P2Y1 receptor in prevention and treatment of anti-depression symptom and/or anti-anxiety symptom
  • Application of P2Y1 receptor and blocking agent of P2Y1 receptor in prevention and treatment of anti-depression symptom and/or anti-anxiety symptom
  • Application of P2Y1 receptor and blocking agent of P2Y1 receptor in prevention and treatment of anti-depression symptom and/or anti-anxiety symptom

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1P2

[0032] Example 1 Pharmacological Experimental Study of Antidepressant and Antianxiety of P2Y1 Receptor Specific Blockers MRS2500 and MRS2179

[0033] 1. Forced swimming test (FST):

[0034] In 1977, Porsolt proposed the forced swimming test, which was first used in rats and later extended to mice. The forced swimming test is used to screen antidepressant drugs, and it is found that antidepressant drugs can reduce the immobility time of forced swimming mice. This model is one of the most commonly used models for screening antidepressant drugs. The experimental steps are as follows: After the experimental mice had adapted to the behavioral laboratory for at least 60 minutes in advance, the following experiments were carried out: a single mouse was placed in a cylindrical glass tank with a water depth of 23 cm (height: 45 cm; diameter: 19 cm), the water temperature At 22-25°C, perform forced swimming for 6 minutes. The accumulated immobility time within 4 minutes after recordin...

Embodiment 2P2Y1

[0045] Example 2 Depression-like behavior screening of P2Y1 receptor knockout mice

[0046] 1. Forced swimming experiment

[0047] Experimental method: P2Y1 receptor whole-body knockout mice and wild-type mice were subjected to a 6-minute forced swimming test, and the swimming immobility time within 4 minutes after that was recorded.

[0048] Experimental animals: P2Y1 mice were purchased from Jax (strain number: 009131). This gene has only one coding exon, and most of the coding regions were disturbed by PGK neo cassette. The resulting 129 chimeric mice were backcrossed with C57BL / 6J 12 generation. The experimental animals were kept in a 12 / 12-hour light-dark environment, free to eat and drink.

[0049] Experimental results: if Figure 5 As shown, the immobility time in the forced swimming test was significantly reduced in P2Y1 receptor knockout mice compared with wild-type mice. The results showed that after the expression level of P2Y1 receptor was downregulated, the mi...

Embodiment 3

[0054] Example 3 The experiment of using RNA interference technology to verify P2Y1 receptor as a new antidepressant target

[0055] Experimental animals: C57BL / 6J mice, SPF grade, male, body weight 20±2g, all animals were provided by Experimental Animal Center of Southern Medical University (Guangzhou, China). The mice were raised in separate cages in an SPF animal breeding room, with 3 to 4 mice per cage, room temperature: 24±1°C; light and dark cycle: 12h / 12h; light time: 7:00am~7:00pm; relative humidity: 70~ 85%; the indoor environment is quiet, and mice can eat and drink freely. The experiments were carried out from 1:00 to 5:00 in the afternoon. Before the experiment, the mice would enter the experimental environment in advance to adapt, and the experimenters would touch them to adapt.

[0056] Experimental method: Microinject 0.5ul (0.1ul) of interfering RNA molecule adeno-associated virus (shRNA) into the ventral dorsal tegmental region (angle 7°, AP: -3.2mm, ML: 1.0m...

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Abstract

The present invention discloses application of a P2Y1 receptor and a blocking agent of the P2Y1 receptor in prevention and treatment of an anti-depression symptom and / or an anti-anxiety symptom. According to the experimental study, it is confirmed that the P2Y1 receptor can be used for screening drugs of the anti-depression symptom and / or the anti-anxiety symptom, and can further be used for screening of the depression symptom and / or the anxiety symptom and early warning of the depression symptom and / or the anxiety symptom. The blocking agent of the P2Y1 receptor has anti-depression and anti-anxiety effects and can be used for preparing drugs of the anti-depression symptom and / or the anti-anxiety symptom.

Description

technical field [0001] The invention relates to the technical field of biopharmaceutical medicine, in particular to a method for screening antidepressant and / or anti-anxiety diseases and medicines thereof with P2Y1 receptor as a target, or using a blocker of P2Y1 receptor for the preparation of antidepressant and / or anti-anxiety medications. Background technique [0002] Depression is the most common mood disorder, which seriously threatens human mental and physical health. Depression is a type of mood disorder syndrome characterized by low mood, impaired cognitive function, and decreased willpower. It has the characteristics of high incidence, high disability rate, and heavy burden. According to the World Health Organization, the estimated incidence It is 15-17%, and it has a rising trend. It is predicted that it will become the first cause of disability in the world in 2020. Depression not only seriously threatens the patient's personal health and life, but also imposes ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/675A61P25/22A61P25/24
CPCA61K31/7076A61K31/675A61K45/00A61P25/24A61P25/22G01N33/6896G01N2500/04
Inventor 高天明王倩孔颖吴定宇杨建明
Owner SOUTHERN MEDICAL UNIVERSITY
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