ADMINISTRATION OF THE NEW COMT INHIBITOR OR-611 INCREASES STRIATAL UPTAKE OF FLUORODOPA

被引:50
作者
GUTTMAN, M
LEGER, G
RECHES, A
EVANS, A
KUWABARA, H
CEDARBAUM, JM
GJEDDE, A
机构
[1] MCGILL UNIV,MONTREAL NEUROL INST,DEPT NEUROL & NEUROSURG,MONTREAL H3A 2B4,QUEBEC,CANADA
[2] HADASSAH HEBREW UNIV HOSP,DEPT NEUROL,JERUSALEM,ISRAEL
[3] CORNELL UNIV,BURKE REHAB CTR,DEPT NEUROL & NEUROSCI,WHITE PLAINS,NY 10605
关键词
COMT; PET; FLUORODOPA; PARKINSONS DISEASE; PRIMATES;
D O I
10.1002/mds.870080308
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
L-Dopa is metabolized to 3-O-methyldopa (3OMD) by catechol-O-methyltransferase (COMT). This reduces the amount of L-dopa available for entry into brain. We studied the effect of OR-611, a new COMT inhibitor, on plasma and brain 6-[F-18]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methyltluorodopa (3OMFD). PET measurements of striatal 6FD concentrations showed an average 2.3-fold increase following OR-611 pretreatment, compared to the same animals in the control state. OR-611 inhibits plasma metabolism of 6FD and increases brain uptake of this L-dopa analog. OR-611 appears to be a promising agent as an adjunct to L-dopa for the treatment of patients with Parkinson's disease.
引用
收藏
页码:298 / 304
页数:7
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