以神经递质为靶点的抗阿尔茨海默病药物研发进展

Progress in drug development of Alzheimer's diseasetargeting neurotransmitters

阿尔茨海默病(Alzheimer's disease,AD)是一种慢性致死性神经退行性疾病。目前美国食品药品监督管理局(FDA)批准上市的5种药物为胆碱酯酶抑制剂(他克林、多奈哌齐、利斯的明、加兰他敏)和N-甲基-D天冬氨酸受体拮抗剂(美金刚),均以神经递质为靶点。根据Alzforum数据库显示,共有68个靶向神经递质的小分子进入临床研究,因各种原因很多小分子化合物已经撤市。对截止2023年1月份为止仍然处于临床研究的23个以神经递质为靶点的化合物进行综述,为研究开发抗AD药物提供思路。

Alzheimer's disease(AD)is a fatal chronic neurodegenerative disease.Five drugs approved by FDA are all based on neurotransmitter disorders,including cholinesterase inhibitors(taclaline,donepezil,rivastigmine and galantamine)and N-methyl-D-aspartate receptor antagonist(memantine).The Alzforum database showed that a total of 68 small molecules targeting neurotransmitters had entered clinical research while some had been discontinued.We reviewed all 23 compounds that are still in clinical research so far and hope to provide ideas for the research and development of anti-AD drugs targeting neurotransmitters.