Psychosis occurs across a wide variety of dementias with differing etiologies, including Alzheimer’s dementia, Parkinson’s dementia, Lewy body dementia, frontotemporal dementia, and vascular dementia. Pimavanserin, a selective serotonin 5-HT_2A receptor (5-HT_2AR) inverse agonist, has shown promising results in clinical trials by reducing the frequency and/or severity of hallucinations and delusions and the risk of relapse of these symptoms in patients with dementia-related psychosis. A literature review was conducted to identify mechanisms that explain the role of 5-HT_2ARs in both the etiology and treatment of dementia-related psychosis. This review revealed that most pathological changes commonly associated with neurodegenerative diseases cause one or more of the following events to occur: reduced synaptic contact of gamma aminobutyric acid (GABA)-ergic interneurons with glutamatergic pyramidal cells, reduced cortical innervation from subcortical structures, and altered 5-HT_2AR expression levels. Each of these events promotes increased pyramidal cell hyperexcitability and disruption of excitatory/inhibitory balance, facilitating emergence of psychotic behaviors. The brain regions affected by these pathological changes largely coincide with areas expressing high levels of 5-HT_2ARs. At the cellular level, 5-HT_2ARs are most highly expressed on cortical glutamatergic pyramidal cells, where they regulate pyramidal cell excitability. The common effects of different neurodegenerative diseases on pyramidal cell excitability together with the close anatomical and functional connection of 5-HT_2ARs to pyramidal cell excitability may explain why suppressing 5-HT_2AR activity could be an effective strategy to treat dementia-related psychosis.

精神病发生在具有不同病因的多种痴呆症中，包括阿尔茨海默病痴呆、帕金森痴呆、路易体痴呆、额颞叶痴呆和血管性痴呆。Pimavanserin 是一种选择性 5-羟色胺 5-HT _2A受体 (5-HT _2A R) 反向激动剂，通过降低幻觉和妄想的频率和/或严重程度以及降低患有这些症状的患者复发的风险，在临床试验中显示出可喜的结果。痴呆相关的精神病。进行了文献回顾以确定解释 5-HT _{2A作用的机制}Rs 在痴呆相关精神病的病因和治疗中。这篇综述揭示了大多数通常与神经退行性疾病相关的病理变化会导致以下一种或多种事件发生：γ-氨基丁酸 (GABA) 能中间神经元与谷氨酸锥体细胞的突触接触减少，皮层下结构的皮层神经支配减少，以及改变5-HT _2AR表达水平。这些事件中的每一个都会促进锥体细胞过度兴奋和兴奋/抑制平衡的破坏，从而促进精神病行为的出现。受这些病理变化影响的大脑区域在很大程度上与表达高水平 5-HT _2A Rs 的区域一致。在细胞水平上，5-HT _2ARs 在皮质谷氨酸能锥体细胞上表达最高，它们调节锥体细胞的兴奋性。不同神经退行性疾病对锥体细胞兴奋性的共同影响以及 5-HT _2A Rs 与锥体细胞兴奋性的密切解剖和功能联系可以解释为什么抑制 5-HT _2A R 活性可能是治疗痴呆相关精神病的有效策略.