Document Detail


Brain extracellular γ-hydroxybutyrate concentrations are decreased by L-lactate in rats: role in the treatment of overdoses.
MedLine Citation:
PMID:  23319173     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Samuel A Roiko; Nisha Vijay; Melanie A Felmlee; Marilyn E Morris
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-01-15
Journal Detail:
Title:  Pharmaceutical research     Volume:  30     ISSN:  1573-904X     ISO Abbreviation:  Pharm. Res.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-09-18     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1338-48     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / drug effects*,  metabolism
Cell Line
Drug Overdose
Humans
Hypnotics and Sedatives / blood,  metabolism,  toxicity*,  urine
Lactic Acid / administration & dosage,  therapeutic use*
Male
Mannitol / administration & dosage,  therapeutic use
Permeability / drug effects
Rats
Rats, Sprague-Dawley
Sleep / drug effects*
Sodium Oxybate / blood,  metabolism,  toxicity*,  urine
Grant Support
ID/Acronym/Agency:
DA023223/DA/NIDA NIH HHS; R01 DA023223/DA/NIDA NIH HHS
Chemical
Reg. No./Substance:
0/Hypnotics and Sedatives; 33X04XA5AT/Lactic Acid; 3OWL53L36A/Mannitol; 502-85-2/Sodium Oxybate
Comments/Corrections

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