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Pharmaceutical composition containing glur2-lacking ampar antagonist for preventing or treating psychiatric illnesses

a technology of glur2-lacking ampar and pharmaceutical composition, which is applied in the direction of drug compositions, biocide, organic chemistry, etc., can solve the problems of not being able to determine whether glur2-lacking ampar antagonists may be effective in the treatment, the most prominent clinical difficulty in repeated memory renewal after treatment, and the difficulty in treating critical ptsd patients. to achieve the effect of preventing or treating mental diseases in subjects, reducing neural activity, and preventing the necros

Inactive Publication Date: 2011-05-05
SEOUL NAT UNIV R&DB FOUND
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0009]A pharmaceutical composition comprising a GluR2-lacking AMPAR antagonist as an active ingredient is useful for preventing or treating mental diseases in a subject since the antagonist prevents the necrosis of brain cells by inhibiting accumulation of calcium (Ca2+), zinc (Zn2+), etc. in the neurons and reduces neural activity of the corresponding brain regions related to the disease.

Problems solved by technology

Although medication therapy is available, only indirect palliatives such as antidepressants are used, which makes it hard to treat critical PTSD patients.
Meanwhile, although there are various methods for treating patients suffering from drug addiction or phobia, repeated memory renewal after the treatment is the most prominent clinical difficulty.
However, it has not been reported whether GluR2-lacking AMPAR antagonists may be effective in the treatment of PTSD, drug addiction or phobia.

Method used

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  • Pharmaceutical composition containing glur2-lacking ampar antagonist for preventing or treating psychiatric illnesses
  • Pharmaceutical composition containing glur2-lacking ampar antagonist for preventing or treating psychiatric illnesses
  • Pharmaceutical composition containing glur2-lacking ampar antagonist for preventing or treating psychiatric illnesses

Examples

Experimental program
Comparison scheme
Effect test

example 1

Accumulation of GluR2-Lacking AMPAR in the Amygdala Synapse by Repeated Retrieval of Fear Memory

[0034]Tests were conducted to examine whether GluR2-lacking AMPAR accumulates in the amygdala synapse by repeated retrieval of fear memory.

example 1-1

Fear Memory Learning, Memory Extinction, and Memory Renewal

[0035]White rats, 4-5 weeks old (Sprague-Dawley Rat, Male; Orient Bio Inc., Korea) were used in the following experiments. All rats were kept while allowing free access to food and water under a 12 hour cycle of light and dark (the light was turned off at 9am).

[0036]For fear memory learning, the rats were exposed to sound stimuli of a single tone (2.8 kHz, 85 dB) for 30 seconds, and subjected to an electric foot shock (1.0 mA) for 1 second at the end of said 30-second period. The sound stimuli and the electric foot shock were repeated 3 times at 100 second intervals. 1 minute later after the last electric foot shock, the rats were returned to their home cages. On day 2, fear memory learning was performed in the same way.

[0037]From day 3, memory extinction was performed in a context different from that of the fear memory learning On day 4, the rats were exposed to only sound stimuli 20 times at 100 second intervals without an...

example 1-2

Preparation of Brain Slices

[0039]The brains of the rats of the group of memory extinction and memory renewal were extracted and placed in a modified artificial cerebrospinal fluid (aCSF). The composition of the modified artificial cerebrospinal fluid used was as follows: 175 mM sucrose, 20 mM NaCl, 3.5 mM KCl, 1.25 mM NaH2PO4, 26 mM NaHCO3, 1.3 mM MgCl2, and 11 mM D-(+)-glucose (Sigma-Aldrich Co., USA). About 3 minutes later, the brains were sliced into 0.3 mm thick slices using a vibroslicer (HA752, Campdem Instruments, Loughborough, UK). The brain slices containing amygdala were cultured in a artificial cerebrospinal fluid (120 mM NaCl, 3.5 mM KCl, 1.25 mM NaH2PO4, 26 mM NaHCO3, 1.3 mM MgCl2, 2 mM CaCl2, 11 mM D-(+)-glucose) containing 95% O2 / 5% CO2 at room temperature for over 1 hour. The cortex overlying the amygdala was removed just before taking it to the equipment for measuring the synaptic reaction.

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Abstract

A pharmaceutical composition, comprising a GluR2-lacking AMPAR antagonist as an active ingredient, is effective for preventing or treating mental diseases selected from the group consisting of posttraumatic stress disorder (PTSD), drug addiction, and phobia.

Description

FIELD OF THE INVENTION[0001]The present invention relates to a pharmaceutical composition for preventing or treating mental diseases, comprising a GluR2-lacking AMPAR antagonist as an active ingredient and a use thereof.BACKGROUND OF THE INVENTION[0002]The treatment of posttraumatic stress disorder (PTSD) has been mostly focused on the alleviation of the symptoms by counseling such as exposure therapy and cognitive restructuring. Although medication therapy is available, only indirect palliatives such as antidepressants are used, which makes it hard to treat critical PTSD patients.[0003]Meanwhile, although there are various methods for treating patients suffering from drug addiction or phobia, repeated memory renewal after the treatment is the most prominent clinical difficulty. Therefore, there exists a need to investigate physiological mechanism of memory renewal for preventing renewal of drug addiction / fear memory.[0004]The α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid rec...

Claims

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Application Information

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IPC IPC(8): A61K31/136C07C211/58A61P25/00A61P25/30
CPCA61K31/137A61K31/165A61P25/00A61P25/22A61P25/28A61P25/30
Inventor CHOI, SUKWOOLEE, SUKWONKIM, JEONGYEONSONG, BEOMJONGHONG, INGIEPARK, SUNGMOKIM, JIHYELEE, JUNUKAN, BOBAESHIN, KISOONPARK, KYUNGJOON
Owner SEOUL NAT UNIV R&DB FOUND
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