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Application of norketamine in preparation of antidepressant drug

A methylketamine, antidepressant technology, applied in the field of antidepressant drug treatment, can solve the problems of large difference, long delayed reaction time, limited duration of drug effect and the like

Inactive Publication Date: 2019-12-13
TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, most of these drugs have large individual differences, limited duration of drug effect, and long delayed response time

Method used

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  • Application of norketamine in preparation of antidepressant drug
  • Application of norketamine in preparation of antidepressant drug
  • Application of norketamine in preparation of antidepressant drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1 Behavioral experiment of LPS-induced mouse depression model

[0029] 1.1 Experimental animals

[0030] Male C57BL / 6J mice (C57 mice, 19-23 g, 8-10 weeks old) were selected. Before modeling, select male C57BL / 6J mice with appropriate aggressiveness, and start the formal modeling experiment after adapting to the SPF laboratory for 3-5 days. Before the experiment, the C57 mice were randomly divided into two groups: the control group (normal), the normal saline group (NS+LPS) and the norketamine group (norketamine+LPS) of different concentrations.

[0031] 1.2 Process of LPS-induced depression model in mice

[0032] The C57 mice were numbered, weighed, grouped, and given a single intraperitoneal injection of LPS (0.5 mg / kg), and 24 hours later were given normal saline and different concentrations of norketamine (5, 10, 20 mg / kg). 1h, 3h, 5h after administration, open field, tail flick and forced swimming experiments were performed.

[0033] 1.3 Depression-like...

Embodiment 2

[0042] Example 2 Contrasting the antidepressant effects of ketamine and norketamine

[0043]The C57 mice were numbered, weighed, grouped, and given a single intraperitoneal injection of LPS (0.5 mg / kg), and then given normal saline, ketamine (10 mg / kg) and norketamine (10 mg / kg) 24 hours later. 1h, 3h, 5h after administration, open field, tail flick and forced swimming experiments were performed. .

[0044] 2.1 Test method

[0045] 2.1 Depression-like behavioral experiment

[0046] Ditto.

[0047] 2.3 Experimental results

[0048] Experimental results: Figure 4 B shows that ketamine and norketamine have no significant effect on the total distance of movement in the open field test of LPS-induced depression mice; Figure 5 It shows that both ketamine and norketamine can reduce the immobility time in the tail flick test of LPS-induced depression mice, compared with NS group, **P Figure 6 It shows that both ketamine and norketamine can reduce the immobility time in LPS-ind...

Embodiment 3

[0050] Example 3 explores the mechanism of norketamine antidepressant

[0051] The C57 mice were numbered, weighed, grouped, and NS, ketamine, and norketamine (5, 10, 20 mg / kg) groups of different concentrations were injected intraperitoneally, and treated with LPS 30 minutes later, and TNF in serum was detected 90 minutes later - alpha concentration.

[0052] The results showed that the serum TNF-α concentration in depressed mice caused by LPS increased, and 10 mg / kg ketamine and 20 mg / kg norketamine could significantly reduce the serum TNF-α concentration ( Figure 7 ).

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Abstract

The invention discloses an application of norketamine in preparation of an antidepressant drug. The antidepressant drug comprises an effective dose of norketamine and pharmaceutically acceptable auxiliary materials. According to the application of the norketamine in preparation of the antidepressant drug, the anti-depression effect of the norketamine is superior to that of ketamine, the depressionsymptoms can be relieved to a certain extent by reducing expression and activity of TNF-alpha, and meanwhile, the side effect of the norketamine is lower than that of the ketamine. The research results show that the norketamine can provide a new antidepressant drug for clinic application.

Description

technical field [0001] The invention relates to the field of antidepressant drug treatment, in particular to the application of norketamine in the preparation of antidepressant drugs. Background technique [0002] Depression is a psycho-emotional disorder with a relatively high incidence, mainly manifested as persistent depression, anhedonia, loss of interest, low self-evaluation, cognitive dysfunction, and avoidance of social activities. Not yet fully elucidated. With the acceleration of the pace of social life and the increase of chronic stress, the incidence of depression is on the rise. According to the report of the World Health Organization, there are about 350 million depression patients in the world, and the annual suicide death rate is as high as 1 million. It is estimated that depression will become the world's first high-burden disease by 2030. [0003] Currently, the main treatment methods for depression include medication, psychotherapy, and physical therapy. ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61P25/24
CPCA61K31/137A61P25/24
Inventor 杨春陈旭辉花冬宇罗爱林万里
Owner TONGJI HOSPITAL ATTACHED TO TONGJI MEDICAL COLLEGE HUAZHONG SCI TECH
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