Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.
Identifieur interne : 004958 ( Ncbi/Curation ); précédent : 004957; suivant : 004959Administration of the new COMT inhibitor OR-611 increases striatal uptake of fluorodopa.
Auteurs : M. Guttman [Canada] ; G. Léger ; A. Reches ; A. Evans ; H. Kuwabara ; J M Cedarbaum ; A. GjeddeSource :
- Movement disorders : official journal of the Movement Disorder Society [ 0885-3185 ] ; 1993.
English descriptors
- KwdEn :
- Animals, Catechols (pharmacokinetics), Catechols (pharmacology), Corpus Striatum (drug effects), Corpus Striatum (metabolism), Corpus Striatum (radionuclide imaging), Dihydroxyphenylalanine (analogs & derivatives), Dihydroxyphenylalanine (metabolism), Fluorine Radioisotopes (metabolism), Levodopa (metabolism), Macaca fascicularis, Magnetic Resonance Imaging, Male, Nitriles, Parkinson Disease (drug therapy), Tomography, Emission-Computed.
- MESH :
- chemical , analogs & derivatives : Dihydroxyphenylalanine.
- chemical , metabolism : Dihydroxyphenylalanine, Fluorine Radioisotopes, Levodopa.
- chemical , pharmacokinetics : Catechols.
- chemical , pharmacology : Catechols.
- drug effects : Corpus Striatum.
- drug therapy : Parkinson Disease.
- metabolism : Corpus Striatum.
- radionuclide imaging : Corpus Striatum.
- Animals, Macaca fascicularis, Magnetic Resonance Imaging, Male, Nitriles, Tomography, Emission-Computed.
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.
DOI: 10.1002/mds.870080308
PubMed: 8341294
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pubmed:8341294Le document en format XML
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Léger</name></author><author><name sortKey="Reches, A" sort="Reches, A" uniqKey="Reches A" first="A" last="Reches">A. Reches</name></author><author><name sortKey="Evans, A" sort="Evans, A" uniqKey="Evans A" first="A" last="Evans">A. Evans</name></author><author><name sortKey="Kuwabara, H" sort="Kuwabara, H" uniqKey="Kuwabara H" first="H" last="Kuwabara">H. Kuwabara</name></author><author><name sortKey="Cedarbaum, J M" sort="Cedarbaum, J M" uniqKey="Cedarbaum J" first="J M" last="Cedarbaum">J M Cedarbaum</name></author><author><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A" last="Gjedde">A. 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Guttman</name><affiliation wicri:level="4"><nlm:affiliation>McConnell Brain Imaging Centre, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>McConnell Brain Imaging Centre, Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec</wicri:regionArea><orgName type="university">Université McGill</orgName><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName></affiliation></author><author><name sortKey="Leger, G" sort="Leger, G" uniqKey="Leger G" first="G" last="Léger">G. Léger</name></author><author><name sortKey="Reches, A" sort="Reches, A" uniqKey="Reches A" first="A" last="Reches">A. Reches</name></author><author><name sortKey="Evans, A" sort="Evans, A" uniqKey="Evans A" first="A" last="Evans">A. Evans</name></author><author><name sortKey="Kuwabara, H" sort="Kuwabara, H" uniqKey="Kuwabara H" first="H" last="Kuwabara">H. Kuwabara</name></author><author><name sortKey="Cedarbaum, J M" sort="Cedarbaum, J M" uniqKey="Cedarbaum J" first="J M" last="Cedarbaum">J M Cedarbaum</name></author><author><name sortKey="Gjedde, A" sort="Gjedde, A" uniqKey="Gjedde A" first="A" last="Gjedde">A. Gjedde</name></author></analytic><series><title level="j">Movement disorders : official journal of the Movement Disorder Society</title><idno type="ISSN">0885-3185</idno><imprint><date when="1993" type="published">1993</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Catechols (pharmacokinetics)</term><term>Catechols (pharmacology)</term><term>Corpus Striatum (drug effects)</term><term>Corpus Striatum (metabolism)</term><term>Corpus Striatum (radionuclide imaging)</term><term>Dihydroxyphenylalanine (analogs & derivatives)</term><term>Dihydroxyphenylalanine (metabolism)</term><term>Fluorine Radioisotopes (metabolism)</term><term>Levodopa (metabolism)</term><term>Macaca fascicularis</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Nitriles</term><term>Parkinson Disease (drug therapy)</term><term>Tomography, Emission-Computed</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Dihydroxyphenylalanine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dihydroxyphenylalanine</term><term>Fluorine Radioisotopes</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Catechols</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Catechols</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Macaca fascicularis</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Nitriles</term><term>Tomography, Emission-Computed</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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