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N-methyl-D-aspartate (NMDA) receptor antagonist peptides and application thereof

A receptor antagonist, aspartic acid technology, applied in the field of N-methyl-D-aspartic acid receptor antagonist polypeptide, can solve problems such as untreated depression

Inactive Publication Date: 2016-12-07
SUZHOU PULUODA BIOLOGICAL SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] However, the current NMDA receptor inhibitors include ketamine and phencyclidine, which have not been used to treat depression

Method used

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  • N-methyl-D-aspartate (NMDA) receptor antagonist peptides and application thereof
  • N-methyl-D-aspartate (NMDA) receptor antagonist peptides and application thereof
  • N-methyl-D-aspartate (NMDA) receptor antagonist peptides and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Inhibitory effect of N-methyl-D-aspartate receptor antagonist polypeptide on N-methyl-D-aspartate receptor current in rat hippocampal neurons.

[0015] The NMDA receptor currents of cultured rat hippocampal neurons were recorded by whole-cell patch technology. Hippocampal neurons were extracted and cultured from SD rat brains within 24 hours of birth, and were cultured in an incubator at 37°C and 5% CO2 for 8-13 days for patch clamp experiments.

[0016] The instrument used for the whole-cell patch clamp recording is CEZ-2400 patch clamp amplifier (Nihon Kohden, Japan), and the inner fluid composition (mmol / L) of the glass microelectrode: KCl 140, CaCl2 1, MgCl2 2, HEPES 10, EGTA 11, ATP 4, adjust pH value to 7.2 with 1M KOH, adjust osmotic pressure to 310mOsm / L with sucrose, electrode resistance 3-5MΩ. External fluid composition for perfusion (mmol / L): NaCl 150, KCl 5, CaCl2 2.5, HEPES 10, D-glucose 10, tetrodotoxin 0.0002, adjust the pH value to 7.4 with 1M NaOH, adj...

Embodiment 2

[0020] Effects of an N-methyl-D-aspartate receptor antagonist polypeptide on a mouse forced-swim stress-despair model.

[0021] Using ICR mice as the test animals, 50 mice, half male and half male, weighing 18-22g, were randomly divided into 5 groups: high-dose group, middle-dose group, low-dose group, positive control group, blank group, Each group l0. The treatment group was subcutaneously injected with the polypeptide of the present invention at doses of 20, 10, and 5 mg / Kg, the control group was given fluoxetine at a dose of 10 mg / Kg, and the blank group was given normal saline for 7 consecutive days. One hour after administration on the seventh day, the mice were subjected to a forced swimming test. The mice were forced to swim in water at 20-25°C for 6 minutes, and the immobility time within 4 minutes after recording was recorded. The time spent floating with the head out of the water is used to evaluate the effect of the polypeptide of the present invention on the mode...

Embodiment 3

[0027] Effects of an N-methyl-D-aspartate receptor antagonist polypeptide on a mouse tail-suspension stress hopelessness model.

[0028] Using ICR mice as the test animals, 50 mice, half male and half male, weighing 18-22g, were randomly divided into 5 groups: high-dose group, middle-dose group, low-dose group, positive control group, blank group, Each group l0. The treatment group was subcutaneously injected with the polypeptide of the present invention at doses of 20, 10, and 5 mg / Kg, the control group was given fluoxetine at a dose of 10 mg / Kg, and the blank group was given normal saline for 7 consecutive days. 1h after administration on the 7th day, the mice were subjected to a tail-suspension test, and the mice were fixed with adhesive tape at a place about 1 cm from the end of their tails, and the mice were kept in a suspended state for 6 minutes, and the immobility time of 4 minutes after recording was used to evaluate this product. Effects of Invention Peptides on a M...

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Abstract

The invention relates to the field of medicine, in particular to N-methyl-D-aspartate (NMDA) receptor antagonist peptides capable of alleviating depressive symptoms. The NMDA receptor antagonist peptides have a brand new sequence. The NMDA receptor antagonist peptides have the advantages that rat hippocampal neurons of NMDA receptor currents can be remarkably inhibited, and the IC50 value is 3.81+ / -0.72mu M. As is shown in pharmacological results, the depressive symptoms of acute and chronic depression animal models can be improved, and the NMDA receptor antagonist peptides can serve as effective candidate treatment for clinical depression.

Description

technical field [0001] The invention relates to N-methyl-D-aspartic acid receptor antagonist polypeptide and application thereof, in particular to a polypeptide capable of inhibiting N-methyl-D-aspartic acid receptor and alleviating depression symptoms. Background technique [0002] Depression is the most concerned mental illness in recent years. Although depression is around us, the proportion of patients receiving treatment is not high. The treatment rate of depression in China is less than 10%, and even in developed countries, it is less than half. Many people regard depression as just a mental state, and this kind of thinking often leads patients to miss the best time for treatment. Due to the stress and lifestyle changes of modern society, the incidence of depression among adults over the age of 20 is increasing at a rate of 11.3% per year. Among adolescents, depression also shows an increasing trend year by year. Depression will be second only to ischemic heart dise...

Claims

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Application Information

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IPC IPC(8): C07K14/00A61K38/16A61P25/24
CPCA61K38/00C07K14/001
Inventor 罗瑞雪
Owner SUZHOU PULUODA BIOLOGICAL SCI & TECH
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