Department of Psychiatry and Behavioral Neuroscience, Saint Louis University School of Medicine , Saint Louis, MO, USA.
Department of Psychiatry & Clinical Psychology, St. George Hospital University Medical Center, Balamand University, Faculty of Medicine , Beirut, Lebanon.
Expert Opin Pharmacother. 2020 Apr;21(6):619-627. doi: 10.1080/14656566.2020.1719066. Epub 2020 Feb 8.
Alzheimer's disease (AD) is a major cause of morbidity worldwide and its prevalence is expected to rise. Previous studies involving compounds that target the accumulation of amyloid β protein have been unsuccessful, renewing interest in therapies directed against intracellular deposits of tau proteins. Derived from methylene blue, hydromethylthionine is a tau aggregation inhibitor that recently emerged as a promising disease-modifying treatment for AD.
Herein, the authors cover the chemistry, pharmacodynamics and pharmacokinetics of hydromethylthionine and its oxidized form methylthionine chloride (MTC) that was first studied, as well as clinical efficacy and safety of hydromethylthionine in the treatment of mild to moderate AD.
Randomized clinical trials with hydromethylthionine failed to show any impact of the doses used on the disease course. Data analysis from a non-randomized cohort showed that a smaller dose of the drug previously thought to be ineffective and used as placebo, prescribed as monotherapy rather than as add-on to AD approved symptomatic therapies may slow cognitive decline. This finding was further confirmed by a pharmacokinetic analysis study showing a dose/response relationship with doses around 16 mg daily. Future trials need to study the pharmacological properties of hydromethylthionine and ascertain the optimal safe and effective dose to be used.
阿尔茨海默病（AD）是全球发病率较高的主要疾病之一，预计其发病率还会上升。之前涉及靶向淀粉样 β 蛋白积累的化合物的研究都没有成功，这重新激发了人们对针对 Tau 蛋白细胞内沉积的疗法的兴趣。甲硫氨酸是一种来源于亚甲蓝的 Tau 聚集抑制剂，最近作为治疗 AD 的一种有前途的疾病修饰疗法而出现。
本文涵盖了甲硫氨酸的化学、药效学和药代动力学及其氧化形式甲硫氨酸氯化物（MTC）的化学、药效学和药代动力学，以及甲硫氨酸在治疗轻度至中度 AD 中的临床疗效和安全性。
甲硫氨酸的随机临床试验未能显示所使用剂量对疾病进程有任何影响。一项非随机队列数据分析显示，以前被认为无效并用作安慰剂的较小剂量药物，作为单药治疗而不是作为 AD 批准的对症治疗的附加治疗，可能会减缓认知能力下降。一项药代动力学分析研究进一步证实了这一发现，该研究表明剂量与每天约 16 毫克的剂量之间存在剂量反应关系。未来的试验需要研究甲硫氨酸的药理学特性，并确定最佳的安全有效剂量。
