Abstract | PURPOSE: METHODS: This study assessed the relationship between plasma concentration of sembragiline and brain MAO-B inhibition in patients with AD and in healthy elderly control (EC) subjects. Positron emission tomography (PET) scans using [11C]- L-deprenyl-D2 radiotracer were performed in ten patients with AD and six EC subjects, who received sembragiline each day for 6-15 days. RESULTS: At steady state, the relationship between sembragiline plasma concentration and MAO-B inhibition resulted in an Emax of ∼80-90 % across brain regions of interest and in an EC50 of 1-2 ng/mL. Data in patients with AD and EC subjects showed that near-maximal inhibition of brain MAO-B was achieved with 1 mg sembragiline daily, regardless of the population, whereas lower doses resulted in lower and variable brain MAO-B inhibition. CONCLUSIONS: This PET study confirmed that daily treatment of at least 1 mg sembragiline resulted in near-maximal inhibition of brain MAO-B enzyme in patients with AD.
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Authors | Stefan Sturm, Anton Forsberg, Stephane Nave, Per Stenkrona, Nicholas Seneca, Andrea Varrone, Robert A Comley, Patrik Fazio, Candice Jamois, Ryuji Nakao, Zbigniew Ejduk, Nabil Al-Tawil, Ulrika Akenine, Christer Halldin, Niels Andreasen, Benedicte Ricci |
Journal | European journal of nuclear medicine and molecular imaging
(Eur J Nucl Med Mol Imaging)
Vol. 44
Issue 3
Pg. 382-391
(Mar 2017)
ISSN: 1619-7089 [Electronic] Germany |
PMID | 27633250
(Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study)
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Chemical References |
- Acetamides
- Monoamine Oxidase Inhibitors
- Pyrrolidinones
- Monoamine Oxidase
- sembragiline
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Topics |
- Acetamides
(blood, pharmacokinetics, therapeutic use)
- Administration, Oral
- Aged
- Alzheimer Disease
(diagnostic imaging, drug therapy)
- Case-Control Studies
- Female
- Humans
- Male
- Middle Aged
- Monoamine Oxidase
(metabolism)
- Monoamine Oxidase Inhibitors
(administration & dosage, pharmacokinetics, therapeutic use)
- Positron-Emission Tomography
- Protein Binding
- Pyrrolidinones
(blood, pharmacokinetics, therapeutic use)
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