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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<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>
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