A mGlu2/3 agonist in the treatment of PTSD

mGlu2/3 激动剂治疗 PTSD

• 批准号: 8650643
• 负责人: ALEXANDER NEUMEISTER
• 金额: $ 1.81万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-09 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650643
• 关键词: Adult; Aftercare; Agonist; Amygdaloid structure; Anxiety; Anxiety Disorders; Arousal; Behavioral; Biological Markers; Chronic; Chronic stress; Clinical; Clinical Trials; Data; Development; Diagnostic; Dimensions; Disease; Disease model; Double-Blind Method; Etiology; Evaluation; Event; Exposure to; Fright; Functional disorder; Generalized Anxiety Disorder; Glutamates; Hippocampus (Brain); Individual; Learning; Major Depressive Disorder; Measures; Medial; Mediating; Modeling; Neuraxis; Neurotransmitters; Norepinephrine; Panic Disorder; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacotherapy; Phase II Clinical Trials; Phenotype; Placebo Control; Placebos; Play; Post-Traumatic Stress Disorders; Prefrontal Cortex; Process; Psychopathology; Public Health; Randomized; Randomized Clinical Trials; Recruitment Activity; Relative (related person); Reporting; Role; Safety; Selective Serotonin Reuptake Inhibitor; Severities; Specificity; Stress; Structure; Substance Use Disorder; Symptoms; Syndrome; System; Work; base; clinical remission; emotion regulation; experience; improved; neural circuit; neuromechanism; neurotransmission; novel; pre-clinical; prevent; public health relevance; receptor; response; suicidal risk; theories

The glutamatergic system plays a role in certain common behavioral manifestations of posttraumatic stress disorder (PTSD), e.g. mechanisms of fear learning and anxious arousal. We propose to evaluate the efficacy of the mGlu2/3 receptor agonist pomaglumetad methionil in treating PTSD in a randomized, double-blind, placebo-controlled, phase II clinical trial. Key endpoints of this trial include structured diagnostic and self- report measures of PTSD and related symptomatology, as well as objective biomarkers of fear acquisition and expression. Evaluation of the differential efficacy of the mGlu2/3 agonist pomaglumetad methionil on symptom clusters that comprise the theory-driven and empirically-supported five-factor phenotypic model of PTSD symptoms will provide greater specificity regarding how this drug differentially modulates unique dimensions of the PTSD phenotype. Given the inhibitory effects of mGlu2/3 receptor agonists on stress-induced NE secretion, we predict that pomaglumetad methionil will have the most pronounced effect in mitigating anxious arousal symptoms.!

神经元能系统在创伤后应激的某些常见行为表现中起作用 创伤后应激障碍（PTSD），例如恐惧学习和焦虑唤醒的机制。我们建议评估 mGlu 2/3受体激动剂pomaglumetad methionil治疗PTSD的随机，双盲， 安慰剂对照II期临床试验。本试验的关键终点包括结构化诊断和自我评估。 报告PTSD和相关神经病学的测量，以及恐惧获得的客观生物标志物， 表情mGlu 2/3激动剂pomaglumetad methionil对症状的差异疗效评价 包括理论驱动和实验支持的PTSD五因素表型模型的聚类 症状将提供更大的特异性，关于这种药物如何差异调节独特的维度， 创伤后应激障碍表型考虑到mGlu 2/3受体激动剂对应激诱导的NE的抑制作用， 分泌，我们预测pomaglumetad甲硫氨酸将有最明显的效果，在减轻焦虑 兴奋症状！