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 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.
Chemistry Department, Brookhaven National Laboratory, Upton, New York 11973.
J S
JS
Fowler
N D
ND
Volkow
J
J
Logan
G J
GJ
Wang
R R
RR
MacGregor
D
D
Schyler
A P
AP
Wolf
N
N
Pappas
D
D
Alexoff
C
C
Shea
D000368:Aged; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D010300:Parkinson Disease / Q000188:drug therapy; D012642:Selegiline / Q000009:adverse effects* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000201:enzymology*; D014055:Tomography, Emission-Computed
D012642:Selegiline; D008995:Monoamine Oxidase