Title:
ANTAGONIST COMPOSITION AND APPLICATION THEREOF IN PREPARATION OF DRUG FOR TREATMENT OF SLEEP DISORDERS WITH CO-MORBID PSYCHIATRIC DISORDERS
Document Type and Number:
WIPO Patent Application WO/2023/125112
Kind Code:
A1
Abstract:
Provided are an antagonist composition and application thereof in the preparation of a drug for treatment of sleep disorders with co-morbid psychiatric disorders; said antagonist composition comprises a CRH receptor antagonist and a glutamic acid receptor antagonist. It is found for the first time that regulation and control of the neuron activity of a subthalamic nucleus adrenocorticotropic hormone-releasing hormone neuron or downstream external globus pallidus region thereof can change REM sleep duration/stability and fear reaction degree, thus indicating that the subthalamic nucleus and the downstream brain region thereof are functional regulation and control targets of patients suffering from mental diseases related to sleep disorder and fear imbalance. It is also found for the first time that the subthalamic nucleus CRH neuron and the glutamic acid neuron have a high coincidence ratio. On the basis of the above discovery, the CRH receptor antagonist is combined with the glutamic acid receptor antagonist to regulate and control the CRH and glutamic acid signal transmission of the external globus pallidus of the subthalamic nucleus, so that the sleep disorder and the psychiatric disorder abnormal co-morbidities related to the fear emotion imbalance are improved.
Inventors:
WANG LIPING (CN)
ZENG YUTING (CN)
ZHAO BINGHAO (CN)
ZENG YUTING (CN)
ZHAO BINGHAO (CN)
Application Number:
PCT/CN2022/140077
Publication Date:
July 06, 2023
Filing Date:
December 19, 2022
Export Citation:
Assignee:
SHENZHEN INST OF ADV TECH CAS (CN)
International Classes:
A61K45/06; A61K31/505; A61K31/519; A61K31/53; A61P25/00; A61P25/20; A61P25/24
Domestic Patent References:
| WO2013160317A2 | 2013-10-31 |
Foreign References:
| CN114225039A | 2022-03-25 | |||
| CN110958879A | 2020-04-03 | |||
| US20030082214A1 | 2003-05-01 |
Other References:
HELD K., KÜNZEL H., ISING M., SCHMID D.A., ZOBEL A., MURCK H., HOLSBOER F., STEIGER A.: "Treatment with the CRH1-receptor-antagonist R121919 improves sleep-EEG in patients with depression", JOURNAL OF PSYCHIATRIC RESEARCH, ELSEVIER LTD., GB, vol. 38, no. 2, 1 March 2004 (2004-03-01), GB , pages 129 - 136, XP093074397, ISSN: 0022-3956, DOI: 10.1016/S0022-3956(03)00076-1
STUTZMANN, J.M. ; LUCAS, M. ; BLANCHARD, J.C. ; LADURON, P.M.: "Riluzole, a glutamate antagonist, enhances slow wave and REM sleep in rats", NEUROSCIENCE LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 88, no. 2, 26 May 1988 (1988-05-26), AMSTERDAM, NL , pages 195 - 200, XP024371336, ISSN: 0304-3940, DOI: 10.1016/0304-3940(88)90125-5
CHEN CHEN ET AL.: "DESIGN AND SYNTHESIS OF A SERIE OF NON-PEPTIDE HIGH AFFINITY HUMAN CORTICOTROPIN-RELEASING FACTOR", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, 1 January 1996 (1996-01-01), US , pages 4358 - 4360, XP002109183, ISSN: 0022-2623, DOI: 10.1021/jm960149e
STUTZMANN, J.M. ; LUCAS, M. ; BLANCHARD, J.C. ; LADURON, P.M.: "Riluzole, a glutamate antagonist, enhances slow wave and REM sleep in rats", NEUROSCIENCE LETTERS, ELSEVIER, AMSTERDAM, NL, vol. 88, no. 2, 26 May 1988 (1988-05-26), AMSTERDAM, NL , pages 195 - 200, XP024371336, ISSN: 0304-3940, DOI: 10.1016/0304-3940(88)90125-5
CHEN CHEN ET AL.: "DESIGN AND SYNTHESIS OF A SERIE OF NON-PEPTIDE HIGH AFFINITY HUMAN CORTICOTROPIN-RELEASING FACTOR", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 39, 1 January 1996 (1996-01-01), US , pages 4358 - 4360, XP002109183, ISSN: 0022-2623, DOI: 10.1021/jm960149e
Attorney, Agent or Firm:
BEIJING ZHONG XUN TONG DA INTELLECTUAL PROPERTY AGENCY CO., LTD. (CN)
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