The 5-HT7 receptor and disorders of the nervous system: an overview.
The 5-HT7 receptor and disorders of the nervous system: an overview.
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DOI：
10.1007/s00213-009-1626-0
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发表时间：
2009-10
影响因子：
3.4
通讯作者：
Hedlund, Peter B.
中科院分区：
文献类型：
--
作者：
Hedlund, Peter B.
5-HT7受体是最近发现的一种G蛋白偶联的5-羟色胺受体。该受体的功能和可能的临床相关性尚未完全了解。本文综述了人类精神和神经疾病动物模型的使用在多大程度上与5-HT7受体有关。这些研究结合使用了针对受体的药理学和遗传学工具来评估对行为的影响。焦虑和精神分裂症的模型产生了好坏参半的结果，在这些障碍中描述的5-HT7受体没有明确的作用。有些数据可用于癫痫、偏头痛和疼痛，但现在得出任何确定的结论还为时过早。有相当多的证据支持5-HT7受体在抑郁症中的作用。在抑郁症模型中，受体的阻断和失活都导致了抗抑郁药样的特征。在睡眠研究中也获得了佐证。特别有趣的是，将抗抑郁药和5-HT7受体拮抗剂结合使用可以增强效果。阿米舒普利的抗抑郁作用很可能是通过5-HT7受体介导的。在临床前动物模型中使用药理学和遗传学工具有力地支持了5-HT7受体在抑郁症中的作用。有间接证据表明，5-HT7受体拮抗剂在抑郁症的临床治疗中是有用的。现有数据还表明，5-HT7受体可能与焦虑、癫痫、疼痛和精神分裂症有关。
The 5-HT7 receptor is a more recently discovered G-protein-coupled receptor for serotonin. The functions and possible clinical relevance of this receptor are not yet fully understood. The present paper reviews to what extent the use of animal models of human psychiatric and neurological disorders have implicated the 5-HT7 receptor in such disorders. The studies have used a combination of pharmacological and genetic tools targeting the receptor to evaluate effects on behavior. Models of anxiety and schizophrenia have yielded mixed results with no clear role for the 5-HT7 receptor described in these disorders. Some data are available for epilepsy, migraine, and pain but it is still very early to draw any definitive conclusions. There is a considerable amount of evidence supporting a role for the 5-HT7 receptor in depression. Both blockade and inactivation of the receptor have resulted in an antidepressant-like profile in models of depression. Supporting evidence has also been obtained in sleep studies. Especially interesting are the augmented effects achieved by combining antidepressants and 5-HT7 receptor antagonists. The antidepressant effect of amisulpride has been shown to most likely be mediated by the 5-HT7 receptor. The use of pharmacological and genetic tools in preclinical animal models strongly supports a role for the 5-HT7 receptor in depression. Indirect evidence exists showing that 5-HT7 receptor antagonism is clinically useful in the treatment of depression. Available data also indicate a possible involvement of the 5-HT7 receptor in anxiety, epilepsy, pain, and schizophrenia.
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