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Monoamine oxidase A imaging in peripheral organs in healthy human subjects
Author(s) -
Fowler Joanna S.,
Logan Jean,
Wang GeneJack,
Franceschi Dinko,
Volkow Nora D.,
Telang Frank,
Pappas Naomi,
Ferrieri Richard,
Shea Colleen,
Garza Victor,
Xu Youwen,
King Payton,
Schlyer David,
Gatley S. John,
Ding YuShin,
Warner Donald,
Netusil Noelwah,
Carter Pauline,
Jayne Millard,
Alexoff David,
Zhu Wei,
Vaska Paul
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10231
Subject(s) - clorgyline , monoamine oxidase , monoamine oxidase b , monoamine neurotransmitter , chemistry , pharmacology , oxidative deamination , in vivo , monoamine oxidase a , human brain , medicine , endocrinology , serotonin , biochemistry , biology , enzyme , psychiatry , receptor , microbiology and biotechnology
Monoamine oxidase (MAO) catalyzes the oxidative deamination of many biogenic and dietary amines. Though studies of MAO have focused mainly on its regulatory role in the brain, MAO in peripheral organs also represents a vast mechanism for detoxifying vasoactive compounds as well as for terminating the action of physiologically active amines, which can cross the blood brain barrier. Indeed, robust central and peripheral MAO activity is a major requirement in the safe use of many CNS drugs, particularly antidepressants, and thus an awareness of the MAO inhibitory potential of drugs is essential in therapeutics. In this study, we examined the feasibility of quantifying MAO A in peripheral organs in healthy human subjects using comparative positron emission tomography (PET) imaging with carbon‐11 (t 1/2 : 20.4 min) labeled clorgyline ([ 11 C]clorgyline) a suicide inactivator of MAO A and its deuterium labeled counterpart ([ 11 C]clorgyline‐D2). Heart, lungs, kidneys, thyroid, and spleen showed a robust deuterium isotope effect characteristic of MAO and the magnitude of the effect was similar to that of trancylcypromine, an irreversible MAO inhibitor used in the treatment of depression. Liver time‐activity curves were not affected by deuterium substitution precluding the estimation of liver MAO in vivo. In organs showing an isotope effect, MAO A is greatest in the lungs and kidneys followed by the thyroid and heart. This method, which has been previously applied in the human brain, opens the possibility to also directly assess the effects of different variables including smoking, dietary substances, drugs, disease, and genetics on peripheral MAO A in humans. Synapse 49:178–187, 2003. Published 2003 Wiley‐Liss, Inc.