阅读说明：本技术 去甲***在制备抗抑郁的药物中的应用 (Application of norketamine in preparation of antidepressant drug ) 是由 杨春 陈旭辉 花冬宇 罗爱林 万里 于 2019-08-02 设计创作，主要内容包括：本发明公开一种去甲氯胺酮在制备抗抑郁的药物中的应用,抗抑郁的药物,它包括有效剂量的去甲氯胺酮和药学上可接受的辅料。本发明去甲氯胺酮在制备抗抑郁的药物中的应用,去甲氯胺酮抗抑郁作用优于氯胺酮,并通过降低TNF-α的表达和活性,在一定程度上可以减轻抑郁症状,同时去甲氯胺酮的副作用低于氯胺酮。研究结果表明,去甲氯胺酮能够为临床上提供了新的抗抑郁药物。(The invention discloses an application of norketamine in preparing an antidepressant drug, which comprises an effective dose of norketamine and pharmaceutically acceptable auxiliary materials. The norketamine provided by the invention is applied to preparation of antidepressant medicines, the antidepressant effect of the norketamine is better than that of the ketamine, the depression symptoms can be relieved to a certain extent by reducing the expression and activity of TNF-alpha, and the side effect of the norketamine is lower than that of the ketamine. Research results show that norketamine can provide a new antidepressant for clinic.)

1. An application of norketamine in preparing antidepressant.

2. An antidepressant drug characterized by: it comprises an effective amount of norketamine.

3. The antidepressant drug according to claim 2, characterized in that: the medicine also comprises pharmaceutically acceptable auxiliary materials.

4. The antidepressant drug according to claim 3, characterized in that: the pharmaceutically acceptable auxiliary materials comprise vitamin C, fructose, amino acid, dextrin, xylitol, sucrose and normal saline.

5. The antidepressant drug according to claim 2 or 3 or 4, characterized in that: in the medicine, the content of norketamine is 5-20 mg/kg.

6. The antidepressant drug according to claim 2 or 3 or 4, characterized in that: the medicine is an injection preparation or an oral preparation.

Technical Field

The invention relates to the field of antidepressant drug treatment, in particular to application of norketamine in preparation of an antidepressant drug.

Background

Depression is a psychoaffective disorder with a high incidence rate, mainly manifested by persistent depressed mood, anhedonia, loss of interest, underself-assessment, cognitive dysfunction, social withdrawal and the like, and the psychopathological mechanism thereof is not completely elucidated at present. With the acceleration of the pace of social life and the increase of chronic stress, the incidence of depression tends to rise. According to the world health organization reporting about 3.5 million depression patients worldwide with up to 100 million suicide deaths per year, depression is expected to become the first high-load disease worldwide by 2030.

The current major treatment modes of depression comprise drug treatment, psychological treatment and physical treatment. The drug treatment aiming at the depression mainly comprises monoamine oxidase inhibitors, tricyclic antidepressants, 5-hydroxytryptamine reuptake inhibitors, norepinephrine reuptake inhibitors and the like. However, most of these drugs have large individual variability, limited duration of drug action, and long delayed response time.

Therefore, it is of great importance to find new drugs for treating depression.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides an application of norketamine in preparing antidepressant medicines.

in order to achieve the purpose, the invention designs an application of norketamine in preparing antidepressant medicines.

Norketamine, english name norketamine, chemical name 2-amino-2- (2-chlorophenyl) cyclohexanone hydrochloride, molecular formula C₁₂H₁₄ClNO & HCl, CAS No:79499-59-5, molecular weight 260.16, chemical structure shown in the following figure:

Modern pharmacological and clinical studies have confirmed that norketamine is one of the main metabolites of ketamine in vivo, ketamine is a non-barbiturate intravenous whole anesthetic and belongs to an N-methyl-D-aspartate (NMDA) receptor non-competitive antagonist, and studies at the beginning of this century have shown that intravenous infusion of ketamine with an intoxicated dose of flax can significantly, rapidly and continuously ameliorate depression.

It has been shown that at the same time point, the norketamine concentration in each tissue is higher than the ketamine concentration, especially in liver, kidney, spleen, brain, urine, and that ketamine enters the body and is metabolized mostly to norketamine. However, ketamine is a common clinical anesthetic, and studies show that it has a good analgesic effect, but ketamine is used as a controlled psychotropic drug, so that the use of ketamine in clinical pain treatment is limited.

In the invention, the norketamine is applied to the treatment of the LPS-induced depression of the mice, firstly, LPS-induced depression models with different concentrations are adopted, and the improvement effect of the norketamine (5,10,20mg/kg) with different concentrations on the depression behaviors of the LPS-induced mice with 0.5mg/kg is observed.

The invention also provides an antidepressant drug which comprises an effective dose of norketamine.

The medicine also comprises pharmaceutically acceptable auxiliary materials. The pharmaceutically acceptable auxiliary materials comprise vitamin C, fructose, amino acid, dextrin, xylitol, sucrose and normal saline.

in the medicine, the content of norketamine is 5-20 mg/kg.

The medicine is injection preparation or oral preparation.

The invention has the beneficial effects that:

The norketamine provided by the invention is applied to preparation of antidepressant medicines, the antidepressant effect of the norketamine is better than that of the ketamine, the depression symptoms can be relieved to a certain extent by reducing the expression and activity of TNF-alpha, and the side effect of the norketamine is lower than that of the ketamine. Research results show that norketamine can provide a new antidepressant for clinic.

Drawings

FIG. 1A is a flow chart of the experiment, and FIG. 1B is a bar graph of the open field exercise experiment of norketamine on LPS-induced depression mice;

FIG. 2 is a bar graph of norketamine in the tail suspension experiment in mice with LPS-induced depression; p <0.05, P <0.01, the difference was statistically significant;

FIG. 3 is a bar graph of norketamine in an experiment of forced swimming in LPS-induced depression mice; p <0.05, P <0.01, the difference was statistically significant;

FIG. 4A is a flow chart of the experiment, and FIG. 4B is a bar graph comparing ketamine with norketamine in open field exercise experiments in LPS-induced depressed mice;

Figure 5 is a bar graph comparing the effect of ketamine with norketamine on LPS-induced depression tail suspension experiments, P <0.01, P <0.001, with statistical differences;

figure 6 is a bar graph comparing the effect of ketamine with norketamine on LPS-induced depression mice forced swim experiments, with P <0.01 and P <0.001, with statistical differences;

Figure 7 is a bar graph comparing the effect of ketamine with different concentrations of norketamine (5,10,20mg/kg) on serum TNF- α concentrations in LPS-induced depressed mice, P <0.01, P <0.001, with statistical differences;

Fig. 8 is a graph comparing ketamine with different concentrations of norketamine (5,10,20mg/kg) versus total distance of locomotion in the open field experiment of normal mice, administered for 10min, 10mg/kg ketamine and 20mg/kg norketamine both increased total distance of locomotion in the open field experiment of mice compared to saline, and the ketamine group was stronger than the 20mg/kg norketamine group compared to saline, # P <0.01 compared to the ketamine group, # P <0.01, the difference was statistically significant.

Figure 9 is a bar graph comparing the effect of ketamine with varying concentrations of norketamine (5,10,20mg/kg) on prepulse inhibition in normal mice, with differences of statistical significance as compared to saline group, # P <0.05, # P <0.01, and ketamine group, # P < 0.01.

Detailed Description

The present invention is described in further detail below with reference to specific examples so as to be understood by those skilled in the art.