MICA: 5-HT4 receptor activation as a novel mechanism of antidepressant action
MICA:5-HT4 受体激活作为抗抑郁作用的新机制
基本信息
- 批准号:MR/P012604/1
- 负责人:
- 金额:$ 118.11万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2017
- 资助国家:英国
- 起止时间:2017 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
People with depression often receive treatment with antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). SSRIs produce activation of all types of serotonin receptors and some of these receptors are thought to mediate side-effects rather than the therapeutic effect of SSRIs. Also activation of certain other serotonin receptors may delay the onset of therapeutic action of the SSRI treatment.Animal experimental studies have suggested that the 5-HT4 serotonin receptor may be important in mediating the antidepressant effects of SSRIs and targeting this receptor directly may work more quickly than conventional SSRI treatment. Carrying out large-scale clinical trials of new agents in depressed patients is costly and time consuming and therefore one would only want to pursue this approach when there was supporting evidence from experimental medicine studies in humans that 5-HT4 receptor drugs may well be useful in depression.We have developed models of emotional processing (psychological tests that measure how people respond to emotional stimuli) that can detect potential antidepressant effects of novel compounds after only a few days of treatment. We therefore plan to use these models to see whether a new drug that selectively activates 5-HT4 receptors can produce antidepressant-like changes in emotional processing after just one week of treatment.We will carry out these studies in two separate groups of depressed patients: first, those who are not taking any antidepressant medication and second, people who have not experienced a good response to their current treatment. Both these clinical situations are where advances in drug treatment are badly needed.Positive results from one or both of these studies will lead on to formal clinical trials of a 5-HT4 receptor agonist drug in depressed patients.
抑郁症患者经常接受抗抑郁药物治疗,如选择性5-羟色胺再摄取抑制剂(SSRIs)。SSRIs可激活所有类型的5-羟色胺受体,其中一些受体被认为是介导副作用,而不是SSRIs的治疗作用。动物实验研究表明,5-HT 4 - 5-羟色胺受体可能在介导SSRI的抗抑郁作用中起重要作用,直接靶向该受体可能比常规SSRI治疗更快起效。在抑郁症患者身上进行大规模的新药临床试验是昂贵和耗时的,因此只有在人类实验医学研究有支持证据表明5-HT 4受体药物可能对抑郁症有用时,人们才会想采用这种方法。(测量人们对情绪刺激的反应的心理测试),可以在治疗几天后检测新型化合物的潜在抗抑郁作用。因此,我们计划使用这些模型来观察一种选择性激活5-HT 4受体的新药是否能在治疗一周后在情绪处理中产生抗抑郁药样的变化。我们将在两组不同的抑郁症患者中进行这些研究:第一组是没有服用任何抗抑郁药的患者,第二组是对目前的治疗反应不佳的患者。这两种临床情况都迫切需要药物治疗的进步。这些研究中的一项或两项的积极结果将导致抑郁症患者的5-HT 4受体激动剂药物的正式临床试验。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
5-HT4 Receptor Agonist Effects on Functional Connectivity in the Human Brain: Implications for Procognitive Action
- DOI:10.1016/j.bpsc.2023.03.014
- 发表时间:2023-11-06
- 期刊:
- 影响因子:5.9
- 作者:de Cates,Angharad N.;Martens,Marieke A. G.;Harmer,Catherine J.
- 通讯作者:Harmer,Catherine J.
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Catherine Harmer其他文献
Antidepressant Effects on Reward Processing: Can We Predict Response?
- DOI:
10.1016/j.biopsych.2020.02.152 - 发表时间:
2020-05-01 - 期刊:
- 影响因子:
- 作者:
Catherine Harmer - 通讯作者:
Catherine Harmer
136. Neural Response to Implicit Emotions as Biomarkers of Clinical Response to SSRI Treatment in Depression
- DOI:
10.1016/j.biopsych.2017.02.148 - 发表时间:
2017-05-15 - 期刊:
- 影响因子:
- 作者:
Beata Godlewska;Michael Browning;Ray Norbury;Artemis Igoumenou;Philip Cowen;Catherine Harmer - 通讯作者:
Catherine Harmer
873. Dissociable Temporal Effects of Bupropion on Behavioural Measures of Emotional and Reward Processing in Major Depressive Disorder
- DOI:
10.1016/j.biopsych.2017.02.598 - 发表时间:
2017-05-15 - 期刊:
- 影响因子:
- 作者:
Annabel Walsh;Michael Browning;Wayne Drevets;Maura Furey;Catherine Harmer - 通讯作者:
Catherine Harmer
118. Perspectives of Teenage Girls on Conversations With Primary Care Providers (PCPs) About Weight, Eating, and Exercise
- DOI:
10.1016/j.jadohealth.2019.11.121 - 发表时间:
2020-02-01 - 期刊:
- 影响因子:
- 作者:
Catherine Harmer;Kristen Larsen;Constance Baldwin;Taylor Starr - 通讯作者:
Taylor Starr
207. A Double-Blind Randomised Study Investigating Ketamine Sustained Effect on Stress Response
一项双盲随机研究:探究氯胺酮对应激反应的持续作用
- DOI:
10.1016/j.biopsych.2025.02.444 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:9.000
- 作者:
Sara Costi;Pilar Artiach Hortelano;Erdem Pulcu;Rupert McShane;Philip Cowen;Catherine Harmer;Susannah Murphy - 通讯作者:
Susannah Murphy
Catherine Harmer的其他文献
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{{ truncateString('Catherine Harmer', 18)}}的其他基金
MICA: An experimental medicine model for fast acting antidepressant drug treatment in treatment resistant depression
MICA:快速作用抗抑郁药物治疗难治性抑郁症的实验医学模型
- 批准号:
MR/S035591/1 - 财政年份:2019
- 资助金额:
$ 118.11万 - 项目类别:
Research Grant
D-cycloserine augmented single-session CBT for panic disorder
D-环丝氨酸增强单次 CBT 治疗恐慌症
- 批准号:
MR/J011878/1 - 财政年份:2012
- 资助金额:
$ 118.11万 - 项目类别:
Research Grant
Cognitive biomarkers of antidepressant drug efficacy
抗抑郁药物疗效的认知生物标志物
- 批准号:
G0801432/1 - 财政年份:2009
- 资助金额:
$ 118.11万 - 项目类别:
Research Grant
A cognitive vaccine for depression: assessment using neurobiological outcomes in experimental medicine models
抑郁症认知疫苗:在实验医学模型中使用神经生物学结果进行评估
- 批准号:
G0701672/1 - 财政年份:2008
- 资助金额:
$ 118.11万 - 项目类别:
Research Grant
Can we integrate cognitive-behavioural and pharmacological theories of anxiety?
我们可以整合焦虑的认知行为和药理学理论吗?
- 批准号:
G0501223/1 - 财政年份:2006
- 资助金额:
$ 118.11万 - 项目类别:
Research Grant
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Role of the 5-HT4 receptor in neurogenic activity of chronic fluoxetine in the dentate gyrus and its association with mature granule cell dematuration
5-HT4受体在齿状回慢性氟西汀神经源性活性中的作用及其与成熟颗粒细胞去成熟的关系
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10319436 - 财政年份:2008
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アデニル酸シクラーゼ促進性ヒト5-HT4受容体の遺伝子構造ならびに機能調節機構
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