用正电子发射断层扫描（PET）和[11C]-L-司来吉兰-D2评估脑中单胺氧化酶B（MAO-B）占有率：一项针对新型MAO-B抑制剂EVT 301的剂量探索研究。
Assessment of MAO-B occupancy in the brain with PET and [11C]-L-deprenyl-D2: a dose-finding study with a novel MAO-B inhibitor, EVT 301.
作者信息
Hirvonen J, Kailajärvi M, Haltia T, Koskimies S, Någren K, Virsu P, Oikonen V, Sipilä H, Ruokoniemi P, Virtanen K, Scheinin M, Rinne J O
机构信息
Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.
出版信息
Clin Pharmacol Ther. 2009 May;85(5):506-12. doi: 10.1038/clpt.2008.241. Epub 2009 Jan 7.
Inhibition of monoamine oxidase type B (MAO-B) activity in the brain is a putative strategy for the treatment of Alzheimer's disease (AD). We performed a dose-selection and validation study of a novel, reversible MAO-B inhibitor, EVT 301. Sixteen healthy volunteers received selegiline (10 mg) or EVT 301 (25, 75, or 150 mg) daily for 7-8 days, and four subjects with AD received 75 mg of EVT 301. MAO-B occupancy in the brain was assessed using positron emission tomography (PET) with [11C]-L-deprenyl-D2. EVT 301 was found to dose-dependently occupy MAO-B in the human brain, with occupancy ranging from 58-78% at a dose of 25 mg to 73-90% at a dose of 150 mg. The corresponding occupancy after selegiline was 77-92%. Determination of MAO-B inhibition in blood platelets underestimated the actual brain occupancy achieved with EVT 301. A daily EVT 301 dose of 75 or 150 mg appears suitable for clinical efficacy studies in patients with AD.
抑制大脑中的单胺氧化酶B（MAO-B）活性是治疗阿尔茨海默病（AD）的一种潜在策略。我们对新型可逆性MAO-B抑制剂EVT 301进行了剂量选择和验证研究。16名健康志愿者每天服用司来吉兰（10 mg）或EVT 301（25、75或150 mg），持续7 - 8天，4名AD患者服用75 mg的EVT 301。使用[11C]-L-司来吉兰-D2正电子发射断层扫描（PET）评估大脑中MAO-B的占有率。发现EVT 301在人脑中对MAO-B的占有率呈剂量依赖性，25 mg剂量时占有率为58 - 78%，150 mg剂量时为73 - 90%。司来吉兰后的相应占有率为77 - 92%。血小板中MAO-B抑制作用的测定低估了EVT 301在大脑中的实际占有率。每日75或150 mg的EVT 301剂量似乎适合用于AD患者的临床疗效研究。
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