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Titolo:
CHIRAL DRUGS - COMPARISON OF THE PHARMACOKINETICS OF [C-11] D-THREO AND I-THREO-METHYLPHENIDATE IN THE HUMAN AND BABOON BRAIN
Autore:
DING YS; FOWLER JS; VOLKOW ND; DEWEY SL; WANG GJ; LOGAN J; GATLEY SJ; PAPPAS N;
Indirizzi:
BROOKHAVEN NATL LAB,DEPT CHEM UPTON NY 11973 BROOKHAVEN NATL LAB,DEPT MED UPTON NY 11973 SUNY STONY BROOK,DEPT PSYCHIAT STONY BROOK NY 11794
Titolo Testata:
Psychopharmacology
fascicolo: 1, volume: 131, anno: 1997,
pagine: 71 - 78
Fonte:
ISI
Lingua:
ENG
Soggetto:
DOPAMINE TRANSPORTERS; RITALINIC ACID; RAT STRIATUM; BINDING; PET; MICRODIALYSIS; ENANTIOMERS; SITES;
Keywords:
METHYLPHENIDATE; RITALIN; DOPAMINE TRANSPORTER; POSITRON EMISSION TOMOGRAPHY; CHIRAL DRUGS; STEREOSELECTIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
Y.S. Ding et al., "CHIRAL DRUGS - COMPARISON OF THE PHARMACOKINETICS OF [C-11] D-THREO AND I-THREO-METHYLPHENIDATE IN THE HUMAN AND BABOON BRAIN", Psychopharmacology, 131(1), 1997, pp. 71-78

Abstract

Methylphenidate (Ritalin) is the most commonly prescribed psychoactive medication for children in the US where it is used for the treatmentof attention deficit hyperactivity disorder. Methylphenidate is marketed as a racemic mixture of the d-threo and l-threo enantiomers. It isbelieved that the d enantiomer is responsible for the therapeutic effect of methylphenidate. In this study we labeled the individual enantiomers with carbon-11 and compared their binding and pharmacokinetics in the human and baboon brain. Microdialysis studies in the rat were performed to compare their potency cy in elevating striatal dopamine concentration. Positron emission tomographic (PET) studies with [C-11]d-threo-methylphenidate ([C-11]d-threo-MP) demonstrated highest regional uptake in basal ganglia. In contrast, [C-11]l-threo-methylphenidate ([C-11]l-threo-MP) displayed similar uptakes in all brain regions. The ratios of distribution volumes at the steady-state for the basal ganglia to cerebellum (DVBG/DVCB) ranged from 2.2 to 3.3 for [C-11]d-threo-MP in baboon and human, and only 1.1 for [C-11]l-threo-MP. Pretreatmentwith unlabeled methylphenidate (0.5 mg/kg) or GBR12909 (3.5 mg/kg) markedly reduced the striatal but not the cerebellar uptake of [C-11]d-threo-MP, whereas there was no effect on DVBG/DVCB for [C-11]l-threo-MP. In the rat, d-threo-MP increased extracellular dopamine concentration by 650% whereas l-threo-MP did not affect dopamine levels. These results indicate that pharmacological specificity of MP resides entirely in the d-threo isomer and directly show that binding of the l-isomer in human brain is mostly nonspecific.

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Documento generato il 04/04/20 alle ore 11:48:05