| Brain Extracellular γ-hydroxybutyrate Concentrations are Decreased by L-lactate in Rats: Role in the Treatment of Overdoses. | |
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MedLine Citation:
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PMID: 23319173 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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PURPOSE: L-lactate represents a potential treatment for GHB overdose by inhibiting GHB renal reabsorption mediated by monocarboxylate transporters. Our objective was to assess the dose-dependence of L-lactate treatment, with and without D-mannitol, on GHB toxicokinetics/toxicodynamics (TK/TD). METHODS: Rats were administered GHB 600 mg/kg i.v. with L-lactate (low and high doses), D-mannitol, or L-lactate (low dose) with D-mannitol. GHB-induced sleep time and GHB plasma, urine and brain extracellular fluid (ECF) concentrations (by LC/MS/MS) were determined. The effect of L-lactate and D-mannitol on the uptake and efflux of GHB was assessed in rat brain endothelial RBE4 cells. RESULTS: L-lactate treatment increased GHB renal clearance from 1.4 ± 0.1 ml/min/kg (control) to 2.4 ± 0.2 and 4.7 ± 0.5 ml/min/kg after low and high doses, respectively, and reduced brain ECF AUC values to 65 and 25% of control. Sleep time was decreased from 137 ± 12 min (control) to 91 ± 16 and 55 ± 5 min (low and high L-lactate, respectively). D-mannitol did not alter GHB TK/TD and did not alter L-lactate's effects on GHB TK/TD. L-lactate, but not D-mannitol, inhibited GHB uptake, and increased GHB efflux from RBE4 cells. CONCLUSIONS: L-lactate decreases plasma and brain ECF concentrations of GHB, decreasing sedative/hypnotic effects. |
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Authors:
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Samuel A Roiko; Nisha Vijay; Melanie A Felmlee; Marilyn E Morris |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-15 |
Journal Detail:
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Title: Pharmaceutical research Volume: - ISSN: 1573-904X ISO Abbreviation: Pharm. Res. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8406521 Medline TA: Pharm Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Pharmaceutical Sciences School of Pharmacy and Pharmaceutical Sciences, State University of New York, Buffalo, Buffalo, New York, 14214-8033, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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