Phosphodiesterase as a Target for Cognition Enhancement in Schizophrenia.

IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Current topics in medicinal chemistry Pub Date : 2020-01-01 DOI:10.2174/1568026620666200613202641
Mayasah Y Al-Nema, Anand Gaurav
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引用次数: 10

Abstract

Schizophrenia is a severe mental disorder that affects more than 1% of the population worldwide. Dopamine system dysfunction and alterations in glutamatergic neurotransmission are strongly implicated in the aetiology of schizophrenia. To date, antipsychotic drugs are the only available treatment for the symptoms of schizophrenia. These medications, which act as D2-receptor antagonist, adequately address the positive symptoms of the disease, but they fail to improve the negative symptoms and cognitive impairment. In schizophrenia, cognitive impairment is a core feature of the disorder. Therefore, the treatment of cognitive impairment and the other symptoms related to schizophrenia remains a significant unmet medical need. Currently, phosphodiesterases (PDEs) are considered the best drug target for the treatment of schizophrenia since many PDE subfamilies are abundant in the brain regions that are relevant to cognition. Thus, this review aims to illustrate the mechanism of PDEs in treating the symptoms of schizophrenia and summarises the encouraging results of PDE inhibitors as anti-schizophrenic drugs in preclinical and clinical studies.

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磷酸二酯酶作为精神分裂症认知增强的靶点。
精神分裂症是一种严重的精神障碍,影响着全世界1%以上的人口。多巴胺系统功能障碍和谷氨酸能神经传递的改变与精神分裂症的病因密切相关。到目前为止,抗精神病药物是治疗精神分裂症症状的唯一有效方法。这些药物,作为d2受体拮抗剂,充分解决疾病的阳性症状,但他们不能改善阴性症状和认知障碍。在精神分裂症中,认知障碍是该疾病的一个核心特征。因此,对认知障碍和其他精神分裂症相关症状的治疗仍然是一个重大的未满足的医疗需求。目前,磷酸二酯酶(PDEs)被认为是治疗精神分裂症的最佳药物靶点,因为许多PDE亚家族在与认知相关的大脑区域丰富。因此,本文旨在阐述PDE治疗精神分裂症症状的机制,并总结PDE抑制剂作为抗精神分裂症药物在临床前和临床研究中的令人鼓舞的结果。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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