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非典型抗精神病药物的神经生物学和药理学方面

[Neurobiological and pharmacologic aspects of atypical antipsychotic drugs].

作者信息

Sümegi András

机构信息

Vas Megyei Markusovszky Kórház Nonprofit Zrt., Pszichiátriai Centrum, Szombathely.

出版信息

Orv Hetil. 2009 Aug 16;150(33):1539-44. doi: 10.1556/OH.2009.28660.

Abstract

Atypical (second generation) antipsychotic drugs have radically changed and revolutionized the pharmacological treatment of schizophrenia and related disorders. The currently approved atypical antipsychotic drugs, which are available, are characterized by relatively weak affinities for D2-type dopamine receptors and relatively high affinities for 5-HT2A serotonin receptors, when compared with typical (conventional) antipsychotic drugs. The strong interaction with 5-HT2A receptors, with a relative sparing of D2-type dopamine receptors, is likely responsible for the optimal effects of atypical antipsychotic drugs on affective and cognitive symptoms in comparison with conventional antipsychotic drugs. In addition to these actions, several atypical antipsychotic drugs are characterized by a "fast dissociation" rate from D2-dopamine receptors. Mediating special signal transduction pathways, their activity on neuronal survival and plasticity might also contribute to their clinical advantage over typical neuroleptic drugs. By modulating chemical neurotransmission and the intracellular signal transduction systems, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and may have their potential for neuroprotection.

摘要

非典型(第二代)抗精神病药物彻底改变并革新了精神分裂症及相关疾病的药物治疗。与典型(传统)抗精神病药物相比,目前已获批上市的非典型抗精神病药物的特点是对D2型多巴胺受体的亲和力相对较弱,而对5-羟色胺2A(5-HT2A)受体的亲和力相对较高。与传统抗精神病药物相比,与5-HT2A受体的强烈相互作用以及对D2型多巴胺受体的相对保留,可能是导致非典型抗精神病药物对情感和认知症状产生最佳疗效的原因。除了这些作用外,几种非典型抗精神病药物的特点是从D2-多巴胺受体的“快速解离”率。通过介导特殊的信号转导途径,它们对神经元存活和可塑性的作用也可能是其相对于典型抗精神病药物具有临床优势的原因。通过调节化学神经传递和细胞内信号转导系统,抗精神病药物可能会影响多种调节神经元恢复力和活力的功能,并可能具有神经保护潜力。

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