Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

M Guttman; G Léger; A Reches; A Evans; H Kuwabara; J M Cedarbaum; A Gjedde

doi:10.1002/mds.870080308

Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

M Guttman, G Léger, A Reches, A Evans, H Kuwabara, J M Cedarbaum, A Gjedde

40 Citations (Scopus)

Abstract

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-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (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.

Original language	English
Journal	Movement Disorders
Volume	8
Issue number	3
Pages (from-to)	298-304
Number of pages	6
ISSN	0885-3185
DOIs	https://doi.org/10.1002/mds.870080308
Publication status	Published - 1993
Externally published	Yes

Access to Document

10.1002/mds.870080308

Cite this

@article{162bade0b31511debc73000ea68e967b,

title = "Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.",

abstract = "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-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (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.",

author = "M Guttman and G L{\'e}ger and A Reches and A Evans and H Kuwabara and Cedarbaum, {J M} and A Gjedde",

year = "1993",

doi = "10.1002/mds.870080308",

language = "English",

volume = "8",

pages = "298--304",

journal = "Movement Disorders",

issn = "0885-3185",

publisher = "JohnWiley & Sons, Inc.",

number = "3",

}

TY - JOUR

T1 - Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

AU - Guttman, M

AU - Léger, G

AU - Reches, A

AU - Evans, A

AU - Kuwabara, H

AU - Cedarbaum, J M

AU - Gjedde, A

PY - 1993

Y1 - 1993

N2 - 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-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (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.

AB - 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-[18F]-fluoro-L-dopa (6FD) metabolism in cynomolgus monkeys with positron emission tomography (PET). OR-611 pretreatment substantially reduced plasma 6FD metabolism to 3-O-methylfluorodopa (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.

U2 - 10.1002/mds.870080308

DO - 10.1002/mds.870080308

M3 - Journal article

C2 - 8341294

SN - 0885-3185

VL - 8

SP - 298

EP - 304

JO - Movement Disorders

JF - Movement Disorders

IS - 3

ER -

Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.

Abstract

Access to Document

Fingerprint

Cite this