BIOMAT Database Logo BIOMAT Database Logo

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. 2009

J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Turku PET Centre, University of Turku and Turku University Central Hospital, Turku, Finland.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008314 Malonates Derivatives of malonic acid (the structural formula CH2(COOH)2), including its salts and esters.
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D008995 Monoamine Oxidase An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. Amine Oxidase (Flavin-Containing),MAO,MAO-A,MAO-B,Monoamine Oxidase A,Monoamine Oxidase B,Type A Monoamine Oxidase,Type B Monoamine Oxidase,Tyramine Oxidase,MAO A,MAO B,Oxidase, Monoamine,Oxidase, Tyramine
D008996 Monoamine Oxidase Inhibitors A chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines. (From Gilman, et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p414) MAO Inhibitor,MAO Inhibitors,Reversible Inhibitors of Monoamine Oxidase,Monoamine Oxidase Inhibitor,RIMA (Reversible Inhibitor of Monoamine Oxidase A),Reversible Inhibitor of Monoamine Oxidase,Inhibitor, MAO,Inhibitor, Monoamine Oxidase,Inhibitors, MAO,Inhibitors, Monoamine Oxidase
D001792 Blood Platelets Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. Platelets,Thrombocytes,Blood Platelet,Platelet,Platelet, Blood,Platelets, Blood,Thrombocyte
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002250 Carbon Radioisotopes Unstable isotopes of carbon that decay or disintegrate emitting radiation. C atoms with atomic weights 10, 11, and 14-16 are radioactive carbon isotopes. Radioisotopes, Carbon
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females

Related Publications

J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Test-retest reproducibility of [11C]-L-deprenyl-D2 binding to MAO-B in the human brain.
December 2017, EJNMMI research,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Reproducibility of repeated measures of deuterium substituted [11C]L-deprenyl ([11C]L-deprenyl-D2) binding in the human brain.
January 2000, Nuclear medicine and biology,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Evidence for astrocytosis in ALS demonstrated by [11C](L)-deprenyl-D2 PET.
April 2007, Journal of the neurological sciences,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Turnover of monoamine oxidase B (MAO-B) in pig brain by positron emission tomography using 11C-L-deprenyl.
January 1990, Journal of neural transmission. Supplementum,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Activated MAO-B in the brain of Alzheimer patients, demonstrated by [11C]-L-deprenyl using whole hemisphere autoradiography.
January 2011, Neurochemistry international,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Striatal and extrastriatal dopamine D2 receptor occupancy by a novel antipsychotic, blonanserin: a PET study with [11C]raclopride and [11C]FLB 457 in schizophrenia.
April 2013, Journal of clinical psychopharmacology,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Comparison of Early-Phase 11C-Deuterium-l-Deprenyl and 11C-Pittsburgh Compound B PET for Assessing Brain Perfusion in Alzheimer Disease.
July 2016, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Improvement of cognitive function by MAO-B inhibitor L-deprenyl in aged rats.
June 1991, Pharmacology, biochemistry, and behavior,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
Localization of MAO-A and MAO-B in human brain: a step in understanding the therapeutic action of L-deprenyl.
January 1987, Advances in neurology,
J Hirvonen, and M Kailajärvi, and T Haltia, and S Koskimies, and K Någren, and P Virsu, and V Oikonen, and H Sipilä, and P Ruokoniemi, and K Virtanen, and M Scheinin, and J O Rinne
In vivo measurement of brain monoamine oxidase B occupancy by rasagiline, using (11)C-l-deprenyl and PET.
October 2005, Journal of nuclear medicine : official publication, Society of Nuclear Medicine,
Copied contents to your clipboard!