SLOW RECOVERY OF HUMAN BRAIN MAO-B AFTER L-DEPRENYL (SELEGELINE) WITHDRAWAL

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 Parkin son's disease at a dose of 5 mg twice a day. Since enzyme inhibition i s irreversible, the recovery of functional enzyme activity after withd rawal from L-deprenyl requires the synthesis of new enzyme. We have me asured a 40 day half-time for brain MAO B synthesis in Parkinson's dis ease and in normal subjects after withdrawal from L-deprenyl. This is the first measurement of the synthesis rate of a specific protein in t he 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 dis ease. The slow turnover of brain MAO B suggests that the current clini cal dose of L-deprenyl may be excessive and that the clinical efficacy of reduced dosing should be evaluated. Such an evaluation may have me chanistic importance as well as an impact on reducing the side effects and the costs arising from excessive drug use. (C) 1994 Wiley-Liss, I nc.