From pharmacological profiles to clinical outcomes.
From pharmacological profiles to clinical outcomes.
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从药理学概况到临床结果。
DOI：
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发表时间：
2000
影响因子：
2.6
通讯作者：
Robert Kerwin
中科院分区：
文献类型：
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作者：
Robert Kerwin
重新制定的精神分裂症的多巴胺假说认为，大脑边缘区域的多巴胺能神经元过度活动是导致疾病阳性症状的原因。与此同时，额叶皮质中的多巴胺能不活跃被认为是阴性症状和认知障碍的基础。此外，经典的多巴胺能D2受体包括几个不同亚型的家族，其中D2广泛分布，而D3和D4集中在边缘和皮质区域。阿米舒普利选择性地阻断D2和D3受体，但优先于后者。阿米舒普利在突触前受体也有优先活性，而不是突触后受体。因此预测阿米舒普利将缓解额叶皮质的活动不足和边缘系统的活动过度。阿米舒利在其他神经递质的受体上也几乎没有活性。这一独特的药理与阿米舒普利的治疗概况是一致的，阿米舒普利已被清楚地证明可以控制精神分裂症的阳性和阴性症状，具有同等的疗效和良好的耐受性。
The reformulated dopamine hypothesis of schizophrenia postulates that over-activity of dopaminergic neurones in limbic areas of the brain is responsible for the positive symptoms of the illness. At the same time, dopaminergic under-activity in the frontal cortex is thought to underlie the negative symptoms and cognitive impairment. In addition, it has emerged that classical dopaminergic D2 receptors comprise a family of several different subtypes of which D2 is widely distributed, whereas D3 and D4 are concentrated in limbic and cortical areas. Amisulpride selectively blocks D2 and D3 receptors but with preference for the latter. Amisulpride also has preferential activity at presynaptic rather than postsynaptic receptors. It was predicted therefore that amisulpride would alleviate both the under-activity in the frontal cortex and the over-activity in the limbic system. Amisulpride is also virtually free of activity at receptors for other neurotransmitters. This unique pharmacology is consistent with the therapeutic profile of amisulpride, which has been clearly demonstrated to control both the positive and negative symptoms of schizophrenia with equal efficacy as well as being well tolerated.