Chew Zhi Xin, Lim Chooi Ling, Ng Khuen Yen, Chye Soi Moi, Ling Anna Pick Kiong, Koh Rhun Yian
School of Health Sciences, International Medical University, No 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Kuala Lumpur, Malaysia.
School of Pharmacy, Monash University Malaysia, Selangor, Malaysia.
CNS Neurol Disord Drug Targets. 2023;22(3):329-352. doi: 10.2174/1871527321666211231100255.
Parkinson's disease (PD) is a progressive neurodegenerative disease characterised by reduced dopamine levels in the substantial nigra. This may lead to typical motor features such as bradykinesia, resting tremors and rigid muscles, as well as non-motor symptoms such as neuropsychiatric symptoms, sleep disorders, autonomic dysfunction, and sensory disturbances. Inhibitors of monoamine oxidase B (MAO-B) are used to alleviate symptoms by reducing monoamine oxidase-catalysed degradation of dopamine; hence, preserving functional levels of dopamine. The very first MAO-B inhibitor used therapeutically was selegiline, followed by rasagiline, its indane derivative which has superior efficacy and selectivity. Both inhibitors can be used as monotherapy or in combination with other anti- Parkinson drugs. Safinamide, a reversible MAO-B inhibitor that utilises both dopaminergic and non-dopaminergic mechanisms, was recently approved by the European Medicines Agency (EMA) (2015) and U.S. FDA (2017) as an add-on therapy for patients with mid- or late-stage Parkinson's disease. Furthermore, MAO-B inhibitors were found to be associated with potential neuroprotective and disease modifying effects. However, evidence of their efficacy and role in PD models is scarce and warrants further investigation.
帕金森病（PD）是一种进行性神经退行性疾病，其特征是黑质中多巴胺水平降低。这可能导致典型的运动特征，如运动迟缓、静止性震颤和肌肉僵硬，以及非运动症状，如神经精神症状、睡眠障碍、自主神经功能障碍和感觉障碍。单胺氧化酶B（MAO-B）抑制剂通过减少单胺氧化酶催化的多巴胺降解来缓解症状，从而维持多巴胺的功能水平。治疗中使用的第一种MAO-B抑制剂是司来吉兰，其次是其茚满衍生物雷沙吉兰，后者具有更高的疗效和选择性。这两种抑制剂都可以作为单一疗法使用，也可以与其他抗帕金森病药物联合使用。沙芬酰胺是一种可逆的MAO-B抑制剂，它利用多巴胺能和非多巴胺能机制，最近被欧洲药品管理局（EMA）（2015年）和美国食品药品监督管理局（FDA）（2017年）批准作为中晚期帕金森病患者的附加疗法。此外，人们发现MAO-B抑制剂具有潜在的神经保护和疾病修饰作用。然而，它们在帕金森病模型中的疗效和作用证据很少，值得进一步研究。
