Antidepressant Efficacy of Antiglutamatergic Agent
抗谷氨酸药的抗抑郁功效
基本信息
- 批准号:6824387
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:NMDA receptors antidepressants clinical trials data collection methodology /evaluation drug screening /evaluation glutamates human subject inhibitor /antagonist major depression mental disorder chemotherapy neural inhibition neural transmission neuroimaging neuropharmacologic agent neuropsychology neuroregulation patient oriented research pharmacogenetics positron emission tomography receptor sensitivity
项目摘要
Major affective disorders are common, severe, chronic and often life-threatening illnesses. Major depression contributes to significant morbidity and mortality. Impairment in physical and social functioning resulting from depression can be just as severe as other chronic medical illnesses. Suicide is the cause of death in 10-20% of individuals with either bipolar or recurrent depressive disorders.
Despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of patients with major depression fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. Furthermore, a growing body of data suggests that mood disorders are associated with regional volumetric reductions, and cell loss and atrophy. It is thus noteworthy that lamotrigine, which, among other effects reduces glutamate release, has antidepressant effects, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants.
In an open-label study, we tested riluzole, an agent that is Food and Drug Administration-approved for Amyotrophic Lateral Sclerosis that has significant antiglutamatergic and neuroprotective properties in patients with treatment-resistant major depression and found that it had significant antidepressant properties.
Our research now extends to test NMDA antagonists in major depression in a placebo-controlled trial. We are obtaining neuroimaging, neuropsychological, neurophysiological, and genetic data.
重大情感障碍是常见的、严重的、慢性的、常常危及生命的疾病。重度抑郁症会导致严重的发病率和死亡率。抑郁症导致的身体和社会功能障碍可能与其他慢性疾病一样严重。自杀是10-20%双相或复发性抑郁症患者死亡的原因。
项目成果
期刊论文数量(0)
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HUSSEINI K MANJI其他文献
HUSSEINI K MANJI的其他文献
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{{ truncateString('HUSSEINI K MANJI', 18)}}的其他基金
LITHIUM RESPONSIVE BIPOLAR DISORDER AND CNS MYO INOSITOL
锂反应性双相情感障碍和中枢神经系统肌醇
- 批准号:
2908653 - 财政年份:1999
- 资助金额:
-- - 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
- 批准号:
2702902 - 财政年份:1998
- 资助金额:
-- - 项目类别:
PKC SIGNALING AND THE TREATMENT OF BIPOLAR DISORDER
PKC 信号传导和双相情感障碍的治疗
- 批准号:
2891036 - 财政年份:1998
- 资助金额:
-- - 项目类别:
Neuronal-Glial Interaction in the Treatment of Bipolar
双相情感障碍治疗中的神经元-胶质细胞相互作用
- 批准号:
6824400 - 财政年份:
- 资助金额:
-- - 项目类别:
Microarray Studies -- Long Term Treatment for Bipolar
微阵列研究——双相情感障碍的长期治疗
- 批准号:
6824378 - 财政年份:
- 资助金额:
-- - 项目类别:
The Protein Kinase C Inhibitor Tamoxifen in Acute Mania
蛋白激酶 C 抑制剂他莫昔芬治疗急性躁狂症
- 批准号:
6982748 - 财政年份:
- 资助金额:
-- - 项目类别:
Testing whether the enzyme GSK-3 is a therapeutically re
测试 GSK-3 酶是否具有治疗作用
- 批准号:
6984237 - 财政年份:
- 资助金额:
-- - 项目类别:
Glucocorticoid Receptors (GR) in Mitochondria: The Role
糖皮质激素受体 (GR) 在线粒体中的作用
- 批准号:
7312914 - 财政年份:
- 资助金额:
-- - 项目类别:
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