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Titolo:
THERAPEUTIC BRAIN CONCENTRATION OF THE NMDA RECEPTOR ANTAGONIST AMANTADINE
Autore:
KORNHUBER J; QUACK G; DANYSZ W; JELLINGER K; DANIELCZYK W; GSELL W; RIEDERER P;
Indirizzi:
UNIV WURZBURG,DEPT PSYCHIAT,FUCHSLEINSTR 15 D-97080 WURZBURG GERMANY MERZ & CO,DEPT PHARMACOL D-60318 FRANKFURT GERMANY LUDWIG BOLTZMANN INST CLIN NEUROBIOL A-1130 VIENNA AUSTRIA LUDWIG BOLTZMANN INST GERONTOL A-1130 VIENNA AUSTRIA
Titolo Testata:
Neuropharmacology
fascicolo: 7, volume: 34, anno: 1995,
pagine: 713 - 721
SICI:
0028-3908(1995)34:7<713:TBCOTN>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANTIPARKINSONIAN DRUGS MEMANTINE; PARKINSONS-DISEASE; CONTROLLED TRIAL; ION CHANNEL; HYDROCHLORIDE; ACETYLCHOLINE; RELEASE; CELLS; SITE;
Keywords:
N-METHYL-D-ASPARTATE (NMDA); NMDA RECEPTORS; GLUTAMATE; AMINO-ADAMANTANES; AMANTADINE; PARKINSONS DISEASE; HUMAN; POSTMORTEM; BRAIN; CEREBROSPINAL FLUID (CSF); MICRODIALYSIS; PHARMACOKINETIC;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
45
Recensione:
Indirizzi per estratti:
Citazione:
J. Kornhuber et al., "THERAPEUTIC BRAIN CONCENTRATION OF THE NMDA RECEPTOR ANTAGONIST AMANTADINE", Neuropharmacology, 34(7), 1995, pp. 713-721

Abstract

Amantadine (1-amino-adamantane) is clinically used for the managementof Parkinson's disease and drug-induced extrapyramidal symptoms. It has previously been shown that amantadine is a low-affinity uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with rapid blockingand unblocking channel kinetics (K-i-value at the PCP binding site = 10 mu M). The aim of the present studies was to estimate concentrations of amantadine in the central nervous system under therapeutic conditions. In homogenates of postmortem human brain tissue the amantadine concentration appeared to be homogeneously distributed over a wide range of brain areas. Amantadine concentration increased with duration of treatment and decreased with drug-free time. When the duration of treatment was greater than or equal to 10 days and drug-free time less than or equal to 3 days, mean amantadine concentrations in postmortem brain tissue ranged from 48.2 to 386 mu M. In contrast to brain tissue, amantadine concentration in cerebrospinal fluid (CSF) and serum was in the low micromolar range (< 17 mu M). CSF and serum total values were highly correlated to each other and were always lower in CSF. The meanCSF/serum ratio for total amantadine was 0.76. To further estimate the extracellular concentration, amantadine was determined in microdialysates in the rat striatum. At behaviorally active doses, amantadine concentration in striatal microdialysates ranged between 6 and 21 mu M. These results indicate that extracellular concentrations of amantadine(CSF and serum values in patients, striatal microdialysates in the rat) are in the range of its K-i-value at the PCP binding site. Amantadine concentrations in brain tissue are much higher, probably due to intralysosomal accumulation.

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Documento generato il 18/01/20 alle ore 07:26:52