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Titolo:
EFFECTS OF CATECHOL-O-METHYLTRANSFERASE INHIBITION ON THE RATES OF UPTAKE AND REVERSIBILITY OF 6-FLUORO-L-DOPA TRAPPING IN MPTP-INDUCED PARKINSONISM IN MONKEYS
Autore:
DOUDET DJ; CHAN GLY; HOLDEN JE; MORRISON KS; WYATT RJ; RUTH TJ;
Indirizzi:
UNIV BRITISH COLUMBIA,DEPT MED,DIV NEUROL,RM M36,PURDY PAVIL,2211 WESTBROOK MALL VANCOUVER BC V6T 2B5 CANADA UNIV BRITISH COLUMBIA,CTR NEURODEGENERAT DISORDERS VANCOUVER BC V6T 2B5 CANADA UNIV BRITISH COLUMBIA,TRIUMF VANCOUVER BC V6T 2B5 CANADA UNIV WISCONSIN,DEPT MED PHYS MADISON WI 53706 NIMH,NEUROPSYCHIAT BRANCH,NIH,IRP BETHESDA MD 20892
Titolo Testata:
Neuropharmacology
fascicolo: 3, volume: 36, anno: 1997,
pagine: 363 - 371
SICI:
0028-3908(1997)36:3<363:EOCIOT>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; MONOAMINE-OXIDASE-A; L-DOPA; STRIATAL METABOLISM; COMT INHIBITION; DISEASE; BRAIN; PET; 6-)F-18>FLUORO-L-DOPA; NITECAPONE;
Keywords:
FDOPA; PET; TOLCAPONE; COMT INHIBITOR; MPTP-INDUCED PARKINSONISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
31
Recensione:
Indirizzi per estratti:
Citazione:
D.J. Doudet et al., "EFFECTS OF CATECHOL-O-METHYLTRANSFERASE INHIBITION ON THE RATES OF UPTAKE AND REVERSIBILITY OF 6-FLUORO-L-DOPA TRAPPING IN MPTP-INDUCED PARKINSONISM IN MONKEYS", Neuropharmacology, 36(3), 1997, pp. 363-371

Abstract

The uptake rate constant and the loss rate constant that expresses the reversibility of the uptake process of 6-[F-18]fluoro-L-Dopa (FDOPA)were measured by positron emission tomography in the striatum of normal rhesus monkeys and in monkeys with unilateral lesions of the dopaminergic nigro-striatal pathway, induced by intracarotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Each animal was studied twice: with and without pretreatment of the catechol-O-methyltransferase (COMT) inhibitor Po 40-7592, tolcapone. After pretreatment with tolcapone, there was a very significant increase in plasma FDOPA throughout the course of the study, accompanied by a significant decreasein its main metabolite, 3-O-methylfluorodopa. Tolcapone did not induce a significant change in the uptake rate constant in either the normal or the MPTP-treated striatum. However, after tolcapone pretreatment,there was a significant decrease in the loss rate constant in the MPTP-treated striatum (25%) and a smaller, non-significant decrease in the normal striatum (13%). It is concluded that the COMT inhibitor tolcapone exhibits clear peripheral and central activity. As compared to peripheral COMT inhibitors, this central effect may help preserve and stabilize the synaptic levels of DA and, thus, further improve the effects of L-DOPA therapy in parkinsonian patients. (C) 1997 Elsevier Science Ltd.

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Documento generato il 21/09/20 alle ore 03:34:30