多奈哌齐
竞争对手
加兰他明
美金刚
认知功能衰退
医学
神经化学
疾病
兴奋剂
阿尔茨海默病
痴呆
药理学
部分激动剂
神经科学
心理学
内科学
受体
作者
Ramakrishna Nirogi,Grandhi Venkata Ramalingayya,Rajeshbabu Medapati,Narender Ganuga,Renny Abraham,Jagadeesh Babu Thentu,Veera Raghava Chowdary Palacharla,Surendra Petlu,Maheshwari Srirangavaram,Ramkumar Subramanian,Srinivasa Rao Ravella,Shankar Reddy Gagginapally,Vijay Benade,Pradeep Jayarajan,Abdul Rasheed Mohammed
标识
DOI:10.1016/j.ejphar.2023.175625
摘要
Alzheimer's disease (AD) is a progressive neurodegenerative disorder which affects cognitive functions with negative impact on day to day activities and an ultimate loss of independent living. Current standard of care (SOC) for AD, viz. donepezil, rivastigmine, galantamine, memantine etc. either alone or in combination show modest efficacy without changing the course of the disease. On prolonged treatment, side effects are more common with an eventual loss of efficacy. Aducanumab, a monoclonal antibody is a disease modifying therapeutic agent targeting the toxic amyloid beta (Aβ) proteins for its clearance. However, it is found to have only modest efficacy in AD patients and its approval by FDA is controversial. Alternate, effective and safe therapeutics are need of the hour, as AD cases are expected to be doubled by 2050. Recently, 5-HT4 receptors have been envisioned as target for alleviating AD associated cognitive impairment with potential disease modifying ability impacting disease progression. Usmarapride is a 5-HT4 receptor partial agonist, being developed for the possible treatment of AD with symptomatic and disease modifying potential. Usmarapride demonstrated promising effects in ameliorating cognitive deficits in diverse animal models of episodic, working, social, and emotional memories. Usmarapride produced elevation in cortical acetylcholine levels in rats. Furthermore, usmarapride increased levels of soluble amyloid precursor protein alpha, a potential mechanism to reverse toxic Aβ peptide pathology. Usmarapride also potentiated the pharmacological effects of donepezil in animal models. To conclude, usmarapride may be a promising intervention for alleviating the cognitive dysfunction in AD patients with disease modifying potential.
科研通智能强力驱动
Strongly Powered by AbleSci AI