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Metabotropic and ionotropic glutamate receptors as neurobiological targets in anxiety and stress-related disorders: Focus on pharmacology and preclinical translational models

机译:代谢性和离子型谷氨酸受体作为焦虑和胁迫相关疾病的神经生物学靶标:专注于药理学和临床前翻译模型

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摘要

Anxiety disorders are amongst the most common and disabling of psychiatric illnesses and have severe health and socio-economic implications. Despite the availability of a number of treatment options there is still a strong medical need for novel and improved pharmacological approaches in treating these disorders. New developments at the forefront of preclinical research have begun to identify the therapeutic potential of molecular entities integral to the biological response to adversity, particularly molecules and processes that may pre-determine vulnerability or resilience, and those that may act to switch off or "unlearn" a response to an aversive event. The glutamate system is an interesting target in this respect, especially given the impact anxiety disorders have on neuroplasticity, cognition and affective function. These areas of research demonstrate expanding and improved evidence-based options for treating disorders where stress in various guises plays an important etiological role. The current review will discuss how these pathways are involved in fear circuitry of the brain and compare the strength of therapeutic rationale as well as progress towards pharmacological validation of the glutamate pathway towards the treatment of anxiety disorders, with a particular focus on metabotropic and ionotropic glutamate receptors. Specific reference to their anxiolytic actions and efficacy in translational disease models of posttraumatic stress disorder, obsessive-compulsive disorder, panic disorder and phobia will be made. In addition, the availability of ligands necessary to assist clinical proof of concept studies will be discussed.
机译:焦虑症是精神疾病最常见和丧失态度,具有严重的健康和社会经济影响。尽管有许多治疗方案的可用性,但仍然有强烈的医疗需求,并改善治疗这些疾病的药理学方法。临床前研究的最前沿的新进展已经开始识别分子实体对生物反应的分子实体对逆境的治疗潜力,特别是可能预先确定脆弱性或弹性的分子和过程,以及可能采取行动关闭或“未解析”的分子和过程“对厌恶事件的回应。谷氨酸体系是这方面的一个有趣的目标,特别是鉴于影响焦虑症对神经塑性,认知和情感功能的影响。这些研究领域证明了扩大和改进的基于循证选择,以治疗各种顾客的压力发挥重要病因作用。目前的审查将讨论这些途径如何参与大脑的恐惧电路,并比较治疗理由的强度以及对谷氨酸途径的药理验证朝向治疗焦虑症的研究进展,特别关注代谢和离子型谷氨酸受体。特异性提及其抗焦力作用和疗效的翻译疾病模型,将进行强迫症,恐慌症和恐惧症的翻译疾病模型。此外,将讨论协助概念研究临床证明所需的配体的可用性。

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