Pharmaceutical applications for (s)-norketamine and salts thereof

A technology for methylketamine and medicine, which is applied in the directions of medicine combination, medical preparation containing active ingredients, medicine formula, etc.

Pending Publication Date: 2019-08-23
CHIBA UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] In addition, it has also been reported that norketamine exhibits an antidepressant effect although its effect is weaker than that of ketamine (Non-Patent Document 13)

Method used

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  • Pharmaceutical applications for (s)-norketamine and salts thereof
  • Pharmaceutical applications for (s)-norketamine and salts thereof
  • Pharmaceutical applications for (s)-norketamine and salts thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0194] Using an inflammatory animal model of depression (non-patent literature 14-16), the antidepressant effect of norketamine, the main metabolite of ketamine, on the depression-like behavior of the model animals was investigated.

[0195] 1. Materials and Methods

[0196] Norketamine hydrochloride was purchased from Tocris Bioscience (Bristol, UK). Physiological saline was used as a negative control of the drug.

[0197] An inflammatory animal model of depression was created (constructed) by administering lipopolysaccharide (hereinafter abbreviated as LPS) to mice during adulthood. Depression-like behavior was observed in mice given LPS, suggesting that this mouse could serve as a new animal model of depression. The model mice were made by the inventors of the present application and their assistants, and were reported in many papers (Non-Patent Documents 14-16). This model mouse was used as an indicator in the screening of antidepressants in any one of the tail suspensi...

Embodiment 2

[0205] The antidepressant effect of norketamine was compared with that of ketamine. Specifically, using an inflammatory animal model of depression (Non-Patent Documents 14-16), the antidepressant effects of ketamine and norketamine on the depression-like behavior of the model animals were investigated.

[0206] 1. Materials and Methods

[0207] Norketamine hydrochloride was purchased from Tocris Bioscience (Bristol, UK). Ketamine hydrochloride (Ketalar (registered trademark)) was purchased from Daiichi Sankyo Co., Ltd. (Tokyo, Japan). Physiological saline was used as a negative control of the drug.

[0208] An inflammatory animal model of depression was prepared by administering lipopolysaccharide (hereinafter abbreviated as LPS) to the adult mice in the same manner as in Example 1.

[0209] The investigation of the antidepressant effects of ketamine and norketamine was carried out by the behavioral tests of LMT, TST and FST by the same method as that described in Example 1...

Embodiment 3

[0215] A comparative study of the side effects of ketamine and norketamine was carried out by the exercise hyperactivity test and the prepulse suppression test which are evaluation systems for side effects.

[0216] 1. Materials and Methods

[0217] The effects of ketamine and norketamine on the amount of exercise in mice were tested using SCANET MV-40 (MELQUEST Ltd., Toyama, Japan). Specifically, the measurement was performed for a total of 180 minutes from 60 minutes before the administration to 120 minutes after the administration, and the amount of exercise per 10 minutes was calculated. Statistical analysis of the exercise amount results was performed by performing repeated one-way analysis of variance (Repeated one-way ANOVA) followed by least significant difference test (LSD test). Data are presented as mean ± standard deviation (n = 7 or 8 mice / group). The significant difference compared with the group administered with normal saline is represented by **p<0.05, ***p<...

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Abstract

Provided are: a pharmaceutical for preventing and / or treating symptoms of depression, the pharmaceutical comprising (S)-norketamine or a pharmacologically acceptable salt thereof; a pharmaceutical composition for preventing and / or treating symptoms of depression, the composition containing (S)-norketamine or a pharmacologically acceptable salt thereof in an amount effective for alleviating symptoms of depression, and containing substantially no (R)-norketamine; a method for preventing and / or treating symptoms of depression, the method including administering the pharmaceutical or composition;and a use for (S)-norketamine in producing a pharmaceutical for preventing and / or treating symptoms of depression or a composition for preventing and / or treating symptoms of depression.

Description

technical field [0001] The present invention relates to medicaments for the prevention and / or treatment of psychiatric diseases, preferably diseases showing depressive symptoms. More specifically, the present invention relates to prodrugs comprising (S)-norketamine, the optical isomer of norketamine (N-norketamine), (S)-norketamine, or their pharmacologically acceptable Antidepressants (antidepressants) of salts, and prevention of diseases showing depressive symptoms containing (S)-norketamine, prodrugs of (S)-norketamine or their pharmacologically acceptable salts and / or Or therapeutic pharmaceutical composition. [0002] This application claims the priority of Japanese Patent Application No. 2016-210749 which is incorporated herein by reference. Background technique [0003] With changes in social lifestyles and the aging of society, there is an overall tendency for various diseases such as mental illnesses and neurological diseases (nervous system diseases) to increase....

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/135A61K31/357A61K31/661A61P25/22A61P25/24C07C211/29C07D317/24
CPCC07D317/24C07C211/29A61P25/22A61K31/27A61K31/357A61K31/135A61P25/24A61K31/661
Inventor 桥本谦二
Owner CHIBA UNIVERSITY
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