Department of Pharmacy, Southeast University, Dhaka, Bangladesh
Pharmakon Neuroscience Research Network, Dhaka, Bangladesh
Curr Pharm Des. 2020;26(37):4690-4698. doi: 10.2174/1381612826666200406075044.
Alzheimer's disease (AD) is a chronic, age-related, and irreversible brain disorder that typically develops slowly and gets worse over time. The potent auspicious drug candidate for the treatment of AD is supposed to perform the simultaneous modulation of several targets linked to AD. The new therapeutic approach involves drug candidates that are designed to act on multiple targets and have various pharmacological properties. This trend has triggered the development of various multimodal drugs including TV-3326 (i.e. ladostigil) and M-30 (i.e. a new multitarget iron chelator). TV-3326 combines the neurorestorative/neuroprotective effects of the cholinesterase (ChE) inhibitory activity of rivastigmine with rasagiline (a selective monoamine oxidase-B inhibitor and novel antiparkinsonian agent) in a single molecule. M-30, the second derivative of rasagiline, was developed by combining the propargyl moiety of rasagiline into the skeleton of VK-28 (i.e. a novel brain permeable neuroprotective iron chelator). It has been revealed that both the compounds possess anti-AD effects and therefore, the clinical development is directed to the treatment of this type of neurodegenerative diseases (NDs). In this article, we have reviewed the neuroprotective molecular mechanisms and multimodal effects of TV-3326 and M-30.
阿尔茨海默病（AD）是一种慢性、与年龄相关且不可逆转的脑部疾病，通常发展缓慢，随着时间的推移而恶化。治疗 AD 的有效候选药物应该能够同时调节与 AD 相关的多个靶点。新的治疗方法涉及旨在作用于多个靶点并具有多种药理学特性的候选药物。这种趋势引发了各种多模式药物的开发，包括 TV-3326（即拉地昔吉）和 M-30（即新型多靶点铁螯合剂）。TV-3326 将利伐斯的明的胆碱酯酶（ChE）抑制活性的神经修复/神经保护作用与雷沙吉兰（一种选择性单胺氧化酶-B 抑制剂和新型抗帕金森病药物）结合在一个单一分子中。M-30 是雷沙吉兰的第二个衍生物，它是通过将雷沙吉兰的炔丙基部分结合到 VK-28（即一种新型脑穿透性神经保护铁螯合剂）的骨架中而开发的。已经发现这两种化合物都具有抗 AD 作用，因此，临床开发的方向是治疗这种类型的神经退行性疾病（NDs）。在本文中，我们回顾了 TV-3326 和 M-30 的神经保护分子机制和多模式作用。
