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Application of pao as pi4kiiα inhibitor in the preparation of drugs for treating post-traumatic stress disorder

A post-traumatic stress and α-inhibitor technology, which is applied in the field of preparation of drugs for the treatment of post-traumatic stress disorder, can solve the problems of no one reporting, and achieve the effect of good curative effect, small side effects, and great application value

Active Publication Date: 2021-04-27
PEKING UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the therapeutic potential of Pi4KIIα in the field of trauma and stress-related disorders has not been reported yet.

Method used

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  • Application of pao as pi4kiiα inhibitor in the preparation of drugs for treating post-traumatic stress disorder
  • Application of pao as pi4kiiα inhibitor in the preparation of drugs for treating post-traumatic stress disorder
  • Application of pao as pi4kiiα inhibitor in the preparation of drugs for treating post-traumatic stress disorder

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0059] Example 1. Unconditioned stimulus evocation (USR) up-regulates the expression of Pi4KIIα in BLA

[0060] The experimental process is as follows figure 1 shown.

[0061] After 24 hours of fear memory training, the rats were randomly divided into 4 groups, 6 in each group; the 4 groups of animals were (1) no arousal group (NoR); (2) unconditioned stimulus arousal group for 15 minutes (USR 15min ); (3) Unconditioned stimulus evoking group for 1 hour (USR 1h); (4) Unconditioned stimulus evoking group for 4 hours (USR 1h). The brains were decapitated at corresponding time points to detect the expression of Pi4KIIα in BLA.

[0062] The results of western blot experiments were figure 2 As shown, it can be seen that compared with the no arousal group (1.00±0.068), the unconditioned stimulus arousal group 15 minutes group (1.34±0.09), the unconditioned stimulus arousal group 1 hour group (1.32±0.10) and the non-conditioned stimulus arousal group The expression of Pi4KIIα in...

Embodiment 2

[0063] Example 2. Unconditioned stimulus evoking combined administration of PAO significantly inhibited the fear response of rats in the fear memory test

[0064] The experimental process is as follows image 3 shown.

[0065] After 24 hours of fear memory training, the rats were randomly divided into 4 groups, with 8-10 rats in each group; the animals in the 4 groups were (1) the vehicle group was given to the brain area immediately after the unconditioned stimulation was evoked: USR+Vehicle; (2) ) Immediately after the unconditioned stimulus was evoked, the brain area was given PAO1 group: USR+PAO (50 μM); (3) The brain area was given PAO2 immediately after the unconditioned stimulus was evoked: USR+PAO (100 μM); (4) Immediately after the conditioned stimulus was evoked, the brain area was given PAO3 group: USR+PAO (200μM), and the fear memory test was performed 24 hours later.

[0066] The results of the fear memory test were Figure 4 As shown, it can be seen that using...

Embodiment 3

[0067] Example 3. Combined administration of unconditioned stimulation and evocation of PAO inhibits the expression and maintenance of fear memory and the effect is long-lasting

[0068] The experimental process is as follows Figure 5 shown.

[0069]After 24 hours of fear memory training, the rats were randomly divided into 4 groups, with 7-8 rats in each group. The four groups of animals were: (1) vehicle group given to the non-evoked brain area: NoR+Vehicle (1 μL); (2) group given to PAO in the non-evoked brain area: NoR+PAO (200 μM / 1 μL); Immediately after the conditioned stimulus was aroused, the brain area was given vehicle group: USR+Vehicle (1 μL); (4) The brain area was given PAO group immediately after the unconditioned stimulus was aroused: USR+PAO (200 μM / 1 μL). The fear memory test was conducted 24 hours after the intervention to observe the effect of the intervention on the expression of fear memory, and the test was repeated 2 weeks later to observe the long-t...

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Abstract

The invention discloses the application of PAO as a Pi4KIIα inhibitor in the preparation of drugs for treating post-traumatic stress disorder. Specifically, the present invention provides the application of a Pi4KIIα inhibitor in the preparation of a drug for treating post-traumatic stress disorder, and the Pi4KIIα inhibitor can be phenylarsenic oxide; the present invention also provides a drug for treating post-traumatic stress disorder, the active ingredient of which is It is a Pi4KIIα inhibitor, and the Pi4KIIα inhibitor can be phenylarsenic oxide. The Pi4KIIα inhibitor (phenylarsenic oxide) is used as an active ingredient in the preparation of a drug for treating post-traumatic stress disorder, which has the advantages of quick effect, good curative effect and small side effects. The invention has great application value for the treatment of post-traumatic stress disorder.

Description

technical field [0001] The invention relates to a new application of PAO, in particular to the application of PAO as a Pi4KIIα inhibitor in the preparation of drugs for treating post-traumatic stress disorder. Background technique [0002] Post-traumatic stress disorder (PTSD) refers to a delayed and persistent mental disorder caused by an individual's exposure to extremely harmful events (such as war, sexual assault, or traffic accidents, etc.). The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) classifies PTSD under the umbrella of trauma and stress-related disorders. The core symptoms of PTSD are divided into three groups, namely reexperiencing symptoms, avoidance and numbness symptoms, and heightened alertness symptoms. Epidemiological studies have shown that the lifetime prevalence of PTSD ranges from 1.3% to 12.2%, depending on the population studied. PTSD is often associated with multiple mental illnesses such as anxiety, depression, an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/285A61P25/00A61P25/18
CPCA61K31/285A61P25/00A61P25/18
Inventor 陆林郭洪岭章文韩盈时杰朱维莉
Owner PEKING UNIV
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