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Slow recovery of human brain MAO B after L‐Deprenyl (Selegeline) withdrawal
Author(s) -
Fowler Joanna S.,
Volkow Nora D.,
Logan Jean,
Wang GeneJack,
Mac Gregor Robert R.,
Schlyer David,
Wolf Alfred P.,
Pappas Naomi,
Alexoff David,
Shea Colleen,
Dorflinger Ernest,
Kruchowy Lesia,
Yoo Kisook,
Fazzini Enrico,
Patlak Clifford
Publication year - 1994
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.890180203
Subject(s) - selegiline , monoamine oxidase b , monoamine oxidase , parkinson's disease , pharmacology , medicine , drug , enzyme , human brain , disease , chemistry , biochemistry , psychiatry
L‐Deprenyl (Selegeline) is an enzyme‐activated irreversible inhibitor of monoamine oxidase B (MAO B; EC 1.4.3.4). It is used to treat Parkinson's disease at a dose of 5 mg twice a day. Since enzyme inhibition is irreversible, the recovery of functional enzyme activity after withdrawal from L‐deprenyl requires the synthesis of new enzyme. We have measured a 40 day half‐time for brain MAO B synthesis in Parkinson's disease and in normal subjects after withdrawal from L‐deprenyl. This is the first measurement of the synthesis rate of a specific protein in the living human brain. L‐Deprenyl is currently used by 50,000 patients with Parkinson's disease in the United States and its use is expected to increase with reports that it may be beneficial in Alzheimer's disease. The slow turnover of brain MAO B suggests that the current clinical dose of L‐deprenyl may be excessive and that the clinical efficacy of reduced dosing should be evaluated. Such an evaluation may have mechanistic importance as well as an impact on reducing the side effects and the costs arising from excessive drug use. © 1994 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.