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Titolo:
Elevated concentrations of morphine 6-beta-D-glucuronide in brain extracellular fluid despite low blood-brain barrier permeability
Autore:
Stain-Texier, F; Boschi, G; Sandouk, P; Scherrmann, JM;
Indirizzi:
Hop Fernand Widal, INSERM, Unite 26, F-75475 Paris 10, France Hop Fernand Widal Paris France 10 RM, Unite 26, F-75475 Paris 10, France Univ Paris 05, Fac Pharm, Dept Pharmacocinet, F-75270 Paris, France Univ Paris 05 Paris France F-75270 Pharmacocinet, F-75270 Paris, France
Titolo Testata:
BRITISH JOURNAL OF PHARMACOLOGY
fascicolo: 4, volume: 128, anno: 1999,
pagine: 917 - 924
SICI:
0007-1188(199910)128:4<917:ECOM6I>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBROSPINAL-FLUID; RAT-BRAIN; OPIOID-RECEPTOR; ORAL MORPHINE; GUINEA-PIG; MICRODIALYSIS; PLASMA; MORPHINE-6-GLUCURONIDE; METABOLITE; 6-GLUCURONIDE;
Keywords:
morphine; morphine 6-glucuronide (M6G); transcortical microdialysis; extracellular fluid (ECF); intracellular space (ICS); cerebrospinal fluid (CSF); uptake and disposition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Scherrmann, JM Hop Fernand Widal, INSERM, Unite 26, 200 Rue Faubourg St Denis, F-75475 Paris 10, France Hop Fernand Widal 200 Rue Faubourg St Denis Paris France 10
Citazione:
F. Stain-Texier et al., "Elevated concentrations of morphine 6-beta-D-glucuronide in brain extracellular fluid despite low blood-brain barrier permeability", BR J PHARM, 128(4), 1999, pp. 917-924

Abstract

1 This study was done to find out how morphine 6-beta-D-glucuronide (M6G) induces more potent central analgesia than morphine, despite its poor blood-brain barrier (BBB) permeability. The brain uptake and disposition of these compounds were investigated in plasma and in various brain compartments: extracellular fluid (ECF), intracellular space (ICS) and cerebrospinal fluid (CSF).2 Morphine or M6G was given to rats at 10 mg kg(-1) s.c. Transcortical microdialysis was used to assess their distributions in the brain ECF. Conventional tissue homogenization was used to determine the distribution in the cortex and whole brain. These two procedures were combined to estimate drug distribution in the brain ICS. The blood and CSF pharmacokinetics were alsodetermined.3 Plasma concentration data for M6G were much higher than those of morphine, with C-max and AUC 4-5 times more higher, T-max shorter, and V(Z)f(-1) (volume of distribution) and CL f(-1) (clearance) 4-6 times lower. The concentrations of the compounds in various brain compartments also differed: AUCvalues for M6G were lower than those of morphine in tissue and CSF and higher in brain ECF. AUC values in brain show that morphine levels were four times higher in ICS than in ECF, whereas M6G levels were 125 higher in ECF than in ICS.4 Morphine entered brain cells, whereas M6G was almost exclusively extracellular. This high extracellular concentration, coupled with extremely slow diffusion into the CSF, indicates that M6G was predominantly trapped in theextracellular fluid and therefore durably available to bind at opioid receptors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 20/01/20 alle ore 10:30:40