School of Medicinal Sciences and Health Products, Medicinal Chemistry Unit, University of Camerino, via S. Agostino 1, 62032, Camerino, Italy.
School of Medicinal Sciences and Health Products, Telemedicine and Telepharmacy Center University of Camerino via Madonna delle Carceri 9, 62032, Camerino, Italy.
Neuropharmacology. 2021 Jun 1;190:108352. doi: 10.1016/j.neuropharm.2020.108352. Epub 2020 Oct 6.
Alzheimer's disease (AD), the most common cause of adult-onset dementia is characterized by a progressive decline of cognitive functions accompanied by behavioral manifestations. The main class of drugs currently used for the treatment of AD are acetylcholinesterase/cholinesterase inhibitors (ChE-Is). The first ChE-I licensed for symptomatic treatment of AD was tacrine. The ChE-Is currently available in the market are donepezil, rivastigmine and galantamine as tacrine is no longer in use, due to its hepatotoxicity. According to mechanism of action the ChE-Is are classified as short-acting or reversible agents such as tacrine, donepezil, and galantamine, as intermediate-acting or pseudo-irreversible agent such as rivastigmine. Overall, the efficacy of the three ChE-Is available in the market is similar and the benefit of administration of these compounds is mild and may not be clinically significant. Due to gastrointestinal side effects of these drugs, medicinal chemistry and pharmaceutical delivery studies have investigated solutions to improve the pharmacological activity of these compounds. In spite of the limited activity of ChE-Is, waiting for more effective approaches, these drugs still represent a pharmacotherapeutic resource for the treatment of AD. Other approaches in which ChE-Is were investigated is in their use in combination with other classes of drugs such as cholinergic precursors, N-methyl-d-aspartate (NMDA) receptor antagonists and antioxidant agents. After many years from the introduction in therapy of ChE-Is, the combination with other classes of drugs may represent the chance for a renewed interest of ChE-Is in the treatment of adult-onset dementia disorders.
阿尔茨海默病（AD）是最常见的成人发病痴呆的原因，其特征是认知功能逐渐下降，伴有行为表现。目前用于治疗 AD 的主要药物类别是乙酰胆碱酯酶/胆碱酯酶抑制剂（ChE-Is）。第一个获得许可用于 AD 症状治疗的 ChE-I 是他克林。目前市场上可用的 ChE-Is 是多奈哌齐、利斯的明和加兰他敏，因为他克林由于其肝毒性已不再使用。根据作用机制，ChE-Is 分为短效或可逆剂，如他克林、多奈哌齐和加兰他敏，以及中效或拟不可逆剂，如利斯的明。总体而言，市场上可用的三种 ChE-Is 的疗效相似，这些化合物的给药益处温和，可能没有临床意义。由于这些药物存在胃肠道副作用，药物化学和药物输送研究已经研究了改善这些化合物的药理学活性的解决方案。尽管 ChE-Is 的活性有限，但在等待更有效的方法的同时，这些药物仍然是治疗 AD 的药物治疗资源。在 ChE-Is 被研究的其他方法中，它们被用于与其他类别的药物联合使用，如胆碱能前体、N-甲基-D-天冬氨酸（NMDA）受体拮抗剂和抗氧化剂。在 ChE-Is 引入治疗多年后，与其他类别的药物联合使用可能代表 ChE-Is 在治疗成人发病痴呆障碍方面重新受到关注的机会。
