Abstract：
PURPOSE:To investigate if gamma-Hydroxybutyrate (GHB) tolerance is mediated by alterations in GHB systemic pharmacokinetics, transport (blood brain barrier (BBB) and neuronal) or membrane fluidity. MATERIALS AND METHODS:GHB tolerance in rats was attained by repeated GHB administration (5.31 mmol/kg, s.c., QD for 5 days). GHB sedative/hypnotic effects were measured daily. GHB pharmacokinetics were determined on day 5. In separate groups, on day 6, in situ brain perfusion was performed to assess BBB transport alterations; or in vitro studies were performed (fluorescence polarization measurements of neuronal membrane fluidity or [3H]GABA neuronal accumulation). RESULTS:GHB sedative/hypnotic tolerance was observed by day 5. No significant GHB pharmacokinetic or BBB transport differences were observed between treated and control rats. Neuronal membrane preparations from GHB tolerant rats showed a significant decrease in fluorescence polarization (treated-0.320 +/- 0.009, n = 5; control-0.299 +/- 0.009, n = 5; p < 0.05). [3H]GABA neuronal transport Vmax was significantly increased in tolerant rats (2,110.66 +/- 91.06 pmol/mg protein/min vs control (1,612.68 +/- 176.03 pmol/mg protein/min; n = 7 p < 0.05). CONCLUSIONS:Short term GHB administration at moderate doses results in the development of tolerance which is not due to altered systemic pharmacokinetics or altered BBB transport, but might be due to enhanced membrane rigidity and increased GABA reuptake.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Bhattacharya I,Raybon JJ,Boje KMdoi
10.1007/s11095-006-9066-6subject
Has Abstractpub_date
2006-09-01 00:00:00pages
2067-77issue
9eissn
0724-8741issn
1573-904Xjournal_volume
23pub_type
杂志文章abstract：PURPOSE:To identify the molecules responsible for amyloid beta-peptide (1-40) (Abeta(1-40)) uptake by the liver, which play a major role in the systemic clearance of Abeta(1-40). METHODS:The liver uptake index method was used to examine the mechanisms of Abeta(1-40) uptake by the liver in vivo. RESULTS:[125I]Abeta(1-...
journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-006-0208-7
更新日期：2006-07-01 00:00:00
abstract：PURPOSE:To investigate cellular uptake pathways of novel anionic siRNA-lipoplexes as a function of formulation composition. METHODS:Anionic formulations with anionic lipid/Ca(2+)/siRNA ratio of 1.3/2.5/1 (AF1) and 1.3/0.3/1 (AF2) were utilized. Uptake mechanisms were investigated using uptake inhibition and co-localiz...
journal_title：Pharmaceutical research
pub_type： 杂志文章
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：1989-09-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
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更新日期：2000-04-01 00:00:00
abstract：PURPOSE:Interleukin-10 (IL-10) is an anti-inflammatory molecule that has achieved interest as a therapeutic for neuropathic pain. In this work, the potential of plasmid DNA-encoding IL-10 (pDNA-IL-10) slowly released from biodegradable microparticles to provide long-term pain relief in an animal model of neuropathic pa...
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journal_title：Pharmaceutical research
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abstract：PURPOSE:Recently identified organic solute transporter (Ost) alpha and beta are located on the basolateral membrane of enterocytes and may be responsible for the intestinal absorption of many substrates including bile acids. In the present study, the mechanism governing the transcriptional regulation of their expressio...
journal_title：Pharmaceutical research
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更新日期：1988-11-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1991-09-01 00:00:00
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journal_title：Pharmaceutical research
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journal_title：Pharmaceutical research
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更新日期：1998-09-01 00:00:00
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更新日期：2020-01-07 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2018-09-06 00:00:00
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更新日期：2018-05-22 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2011-12-01 00:00:00
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更新日期：2005-10-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：2020-05-21 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1995-04-01 00:00:00
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journal_title：Pharmaceutical research
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更新日期：1990-01-01 00:00:00
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journal_title：Pharmaceutical research
pub_type： 杂志文章
doi：10.1007/s11095-015-1636-z
更新日期：2015-07-01 00:00:00
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更新日期：2008-12-01 00:00:00
