Clinic and Policlinic for Psychiatry, Psychosomatic and Psychotherapy, University of Wuerzburg, 97080 Wuerzburg, Germany.
Exp Neurobiol. 2011 Mar;20(1):1-17. doi: 10.5607/en.2011.20.1.1. Epub 2011 Mar 31.
Monoamine oxidase inhibitors (MAO-I) belong to the earliest drugs tried in Parkinson's disease (PD). They have been used with or without levodopa (L-DOPA). Non-selective MAO-I due to their side-effect/adverse reaction profile, like tranylcypromine have limited use in the treatment of depression in PD, while selective, reversible MAO-A inhibitors are recommended due to their easier clinical handling. For the treatment of akinesia and motor fluctuations selective irreversible MAO-B inhibitors selegiline and rasagiline are recommended. They are safe and well tolerated at the recommended daily doses. Their main differences are related to (1) metabolism, (2) interaction with CYP-enzymes and (3) quantitative properties at the molecular biological/genetic level. Rasagiline is more potent in clinical practise and has a hypothesis driven more favourable side effect/adverse reaction profile due to its metabolism to aminoindan. Both selegiline and rasagiline have a neuroprotective and neurorestaurative potential. A head-to head clinical trial would be of utmost interest from both the clinical outcome and a hypothesis-driven point of view. Selegiline is available as tablet and melting tablet for PD and as transdermal selegiline for depression, while rasagiline is marketed as tablet for PD. In general, the clinical use of MAO-I nowadays is underestimated. There should be more efforts to evaluate their clinical potency as antidepressants and antidementive drugs in addition to the final proof of their disease-modifying potential. In line with this are recent innovative developments of MAO-I plus inhibition of acetylcholine esterase for Alzheimer's disease as well as combined MAO-I and iron chelation for PD.
单胺氧化酶抑制剂（MAO-I）属于最早用于帕金森病（PD）的药物之一。它们可与左旋多巴（L-DOPA）联合或不联合使用。由于非选择性 MAO-I 存在副作用/不良反应，如反苯环丙胺，因此在 PD 抑郁治疗中的应用有限，而选择性、可逆性 MAO-A 抑制剂由于其更易于临床处理而被推荐使用。对于运动不能和运动波动的治疗，推荐使用选择性不可逆 MAO-B 抑制剂司来吉兰和雷沙吉兰。它们在推荐的日剂量下安全且耐受良好。它们的主要区别在于（1）代谢，（2）与 CYP 酶的相互作用，以及（3）分子生物学/遗传水平上的定量特性。在临床实践中，雷沙吉兰更有效，由于其代谢为氨基吲达胺，因此具有假设驱动的更有利的副作用/不良反应谱。司来吉兰和雷沙吉兰均具有神经保护和神经修复潜力。从临床结果和假设驱动的角度来看，进行头对头临床试验将是非常有意义的。司来吉兰可用于治疗 PD 的片剂和融片剂以及用于治疗抑郁症的透皮司来吉兰，而雷沙吉兰则作为 PD 的片剂上市。总的来说，目前 MAO-I 的临床应用被低估了。除了最终证明其具有疾病修饰潜力外，还应该更加努力评估它们作为抗抑郁药和抗痴呆药物的临床效力。最近，MAO-I 加乙酰胆碱酯酶抑制剂用于治疗阿尔茨海默病以及 MAO-I 和铁螯合剂联合用于治疗 PD 的创新发展符合这一趋势。
