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Assessment of MAO‐B Occupancy in the Brain With PET and [ 11 C]‐ L ‐Deprenyl‐D 2 : A Dose‐Finding Study With a Novel MAO‐B Inhibitor, EVT 301
Author(s) -
Hirvonen J,
Kailajärvi M,
Haltia T,
Koskimies S,
Någren K,
Virsu P,
Oikonen V,
Sipilä H,
Ruokoniemi P,
Virtanen K,
Scheinin M,
Rinne JO
Publication year - 2009
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2008.241
Subject(s) - selegiline , monoamine oxidase b , positron emission tomography , pharmacology , monoamine oxidase a , medicine , monoamine oxidase , human brain , nuclear medicine , chemistry , parkinson's disease , disease , psychiatry , biochemistry , enzyme , receptor , serotonin
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 [ 11 C]‐ L ‐deprenyl‐D 2 . 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. Clinical Pharmacology & Therapeutics (2009); 85 , 5, 506–512 doi: 10.1038/clpt.2008.241