神经递质受体在抗精神病药物治疗阿尔茨海默氏症相关精神病疗效中的作用

Bhawana Sharma, Saumya Das, Avijit Mazumder, Deepraj Singh Rautela, Pankaj Kumar Tyagi, Navneet Khurana
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引用次数: 0

摘要

阿尔茨海默病(AD)的特征是认知能力下降,并伴有精神症状,其中最明显的是精神病。虽然抗精神病药物通常被推荐用于治疗这些症状,但人们一直在讨论这些药物对阿尔茨海默病患者的安全性和有效性。阿尔茨海默病相关精神病(ARP)的治疗管理因其治疗方案有限而受到阻碍,要确定阿尔茨海默病患者的精确脑区,就必须了解与 ARP 有关的神经基质。虽然包括布来匹唑和非典型抗精神病药物在内的新疗法提供了很有前景的治疗选择,但我们也讨论了实际实施和即将推出的潜在治疗方法,以及基于机制的对不同神经递质与药物疗法的理解。我们的目标是为在管理和研究 AD 相关精神病领域工作的医疗专业人员和研究人员提供全面的资源,从而为更有效和个性化的治疗方法做出贡献。该研究包含支持以受体为靶点的新型治疗方法的新数据,并具有更好的安全性和有效性特征。这项研究指出了我们现有认识中的不足,并对未来的研究提出了建议,强调了特别针对阿尔茨海默氏症精神病患者进行临床试验的必要性。其次,还详细介绍了 ARP 的神经化学和神经病理学基础,重点是多巴胺、5-羟色胺和谷氨酸神经递质系统的变化。本文后面的章节将介绍不同的药效学抗精神病药物,重点是这些药物与某些神经递质受体的相互作用会如何影响其疗效和副作用。这篇综述文章总结了神经递质受体对抗精神病药物治疗 ADP 的疗效所起作用的最新研究结果。我们全面概述了第二代(非典型)抗精神病药物,强调了它们与神经递质受体的独特亲和力如何影响其在与 AD 相关的精神病中的临床应用。本研究还介绍了使用抗精神病药物治疗阿尔茨海默氏症的困难,包括认知障碍恶化的可能性、锥体外系症状的出现以及其他不利影响。研究和治疗 ARP 的新方法包括神经炎症靶向药物、经颅磁刺激 (TMS)、脑脊液 (CSF) 生物标志物和毒蕈碱乙酰胆碱受体 (mAChR) 激动剂,如沙诺美林。通过了解γ-氨基丁酸(GABA)能神经元中的N-甲基-D-天冬氨酸谷氨酸受体(NMDAR)功能减退过程,可以改善通过治疗方案减少精神病的情况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of neurotransmitter receptors in antipsychotic medication efficacy for Alzheimer’s-related psychosis
Alzheimer's disease (AD) is marked by cognitive decline along with the presence of mental symptoms, most notably psychosis. Although antipsychotic drugs are commonly recommended to treat these symptoms, there is ongoing discussion on the safety and effectiveness of these drugs in AD patients. The therapeutic management of Alzheimer’s disease-related psychosis (ARP) is hampered by its limited therapy options, determining the precise brain regions in Alzheimer’s patients with understanding of the neurological substrates implicated in ARP. While new therapies including brexpiprazole and atypical antipsychotics present promising therapeutic choices, practical implementation and potential upcoming therapies approaches is discussed along with mechanism-based understanding of different neurotransmitters with pharmaceutical therapies. Our objective is to contribute to more efficient and individualized treatment approaches by offering a thorough resource for medical professionals and researchers working in the field of managing and researching psychosis associated with AD. The examination containing new data supporting newer therapeutic approaches that target receptors and providing better safety and effectiveness characteristics. This study point out gaps in our existing understanding and make recommendations for future research, emphasizing the necessity of clinical trials created especially for psychotic Alzheimer’s patients. Secondly, the neurochemical and neuropathological bases of ARP, with a focus on changes in the dopamine, serotonin, and glutamate systems of neurotransmitters are also described in detail. Different pharmacodynamics antipsychotic medications are covered in later sections of this paper, with an emphasis on how these medications' interactions with certain neurotransmitter receptors may affect their therapeutic efficacy and side-effects profile. The review article summarizes the most recent findings regarding the contribution of neurotransmitter receptors to the effectiveness of antipsychotic drugs in the management of ADP. We provide a thorough overview of second-generation (atypical) antipsychotics, emphasizing how their unique affinity for neurotransmitter receptors influences their clinical application in psychosis associated with AD. The difficulties of treating Alzheimer’s with antipsychotics are also covered in this study, including the potential for cognitive impairment to worsen, the emergence of extrapyramidal symptoms, and other unfavorable effects. New approaches to studying and treating ARP including neuroinflammation-targeting medicines, transcranial magnetic stimulation (TMS), cerebrospinal fluid (CSF) biomarkers, and muscarinic acetylcholine receptor (mAChR) agonists like xanomeline. Reducing psychosis through treatment options could be improved by knowledge of N-methyl-D-aspartate glutamate receptors (NMDAR) hypofunction processes in gamma-aminobutyric acid (GABAergic) neurons.
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