Eve Topf Centre of Excellence for Neurodegenerative Diseases and Department of Molecular Pharmacology, Technion-Rappaport Faculty of Medicine, Efron Street, P.O. Box 9697, Haifa, Israel.
Int Rev Neurobiol. 2011;100:191-215. doi: 10.1016/B978-0-12-386467-3.00010-8.
The novel therapeutic strategy in which drug candidates are designed to possess diverse pharmacological properties and act on multiple targets has stimulated the development of the multimodal drug, ladostigil [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate]. Ladostigil combines neuroprotective effects with monoamine oxidase-A and -B and cholinesterase inhibitory activities in a single molecule, presently in a Phase IIb clinical trial and intended for the treatment of Alzheimer's disease, and dementia comorbid with extrapyramidal disorders and depression. This chapter will discuss the preclinical scientific evidence for the therapeutic potential use of ladostigil in the clinic and molecular signaling pathways that are considered to be involved in the molecular activities of the drug.
新型治疗策略旨在使候选药物具有多种药理学特性并作用于多个靶点,这激发了多模式药物拉多替吉((N-丙炔基-(3R)氨基茚满-5-基)-乙基甲基氨基甲酸酯)的发展。拉多替吉在单个分子中结合了神经保护作用、单胺氧化酶-A 和 -B 以及胆碱酯酶抑制活性,目前正处于 IIb 期临床试验阶段,旨在治疗阿尔茨海默病以及伴有锥体外系疾病和抑郁症的痴呆症。本章将讨论拉多替吉在临床中的治疗潜力的临床前科学证据,以及被认为与药物分子活性相关的分子信号通路。