Determination of GABA, glutamate and carbamathione in brain microdialysis samples by capillary electrophoresis with fluorescence detection.
Disulfiram has been used as a deterrent in the treatment of alcohol abuse for almost 60 years. Our laboratory has shown that a disulfiram metabolite, S-(N,N-diethylcarbamoyl) glutathione (carbamathione), is formed from disulfiram and appears in the brain after the administration of disulfiram. Carbamathione does not inhibit aldehyde dehydrogenase but has been shown to be a partial non-competitive inhibitor of the N-methyl-D-aspartic acid glutamate (Glu) receptor. In light of disulfiram's apparent clinical effectiveness in cocaine dependence, and carbamathione's effect on the N-methyl-D-aspartic acid receptor, the effect of carbamathione on brain Glu and γ-aminobutyric acid (GABA) needs to be further examined. A CE-LIF method based on derivatization with napthalene-2,3-dicarboxyaldehyde to simultaneously detect both neurotransmitter amino acids and carbamathione in brain microdialysis samples is described. The separation of Glu, GABA and carbamathione was carried out using a 50 mmol/L boric acid buffer (pH 9.6) on a 75 cm×50 μm id fused-silica capillary (60 cm effective) at +27.5 kV voltage with a run time of 11 min. The detection limits for Glu, GABA and carbamathione were 6, 10 and 15 nmol/L, respectively. This method was used to monitor carbamathione and the amino acid neurotransmitters in brain microdialysis samples from the nucleus accumbens after the administration of an intravenous dose of the drug (200 mg/kg) and revealed a carbamathione-induced change in GABA and Glu levels. This method demonstrates a simple, rapid and accurate measurement of two amino acid neurotransmitters and carbamathione for in vivo monitoring in the brain using microdialysis sampling.
Ralph N. Adams Institute for Bioanalytical Chemistry, Department of Chemistry, University of Kansas, Lawrence, KS, USA.
Swetha
S
Kaul
Morris D
MD
Faiman
Craig E
CE
Lunte
D000818:Animals; D001921:Brain / Q000378:metabolism*; D019075:Electrophoresis, Capillary / Q000379:methods*; D005453:Fluorescence; D018698:Glutamic Acid / Q000032:analysis* / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000032:analysis* / Q000378:metabolism
C546728:carbamathione; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005978:Glutathione
Anal Biochem. 2003 Nov 1;322(1):68-78
14705782
J Chromatogr B Biomed Sci Appl. 2001 Jun 15;757(2):277-83
11417872
Drug Metab Dispos. 1995 Oct;23(10):1153-62
8654205
J Biol Chem. 1997 Sep 26;272(39):24247-51
9305877
Lancet. 1948 Dec 25;2(6539):1001-4
18103475
Addiction. 2000 Feb;95(2):219-28
10723850
Anal Chem. 1995 Feb 1;67(3):594-9
7893003
Biochem Pharmacol. 1994 Apr 20;47(8):1465-7
8185656
J Neurosci. 2001 Nov 1;21(21):8655-63
11606653
J Neurosci. 1997 Apr 15;17(8):2921-7
9092613
Chem Res Toxicol. 1994 Jul-Aug;7(4):526-33
7981417
Neuropsychopharmacology. 2008 Nov;33(12):2934-45
18418367
Annu Rev Psychol. 2008;59:29-53
18154498
J Pharmacol Exp Ther. 1995 Feb;272(2):775-80
7853193
Mol Biosyst. 2005 Jul;1(2):127-34
16880974
Synapse. 1998 Oct;30(2):119-29
9723781
Cell Mol Neurobiol. 2003 Oct;23(4-5):793-804
14514032
J Chromatogr A. 2008 Sep 26;1205(1-2):144-9
18752800
J Biomed Sci. 2001 Jan-Feb;8(1):104-13
11173983
Pharm Res. 1991 Apr;8(4):421-6
1871036
Addiction. 2000 Sep;95(9):1335-49
11048353
J Pharm Biomed Anal. 2010 Jan 5;51(1):186-91
19709836
J Neurosci Methods. 1995 Mar;57(1):47-53
7791364
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jul 5;806(2):237-44
15171934
Neurochem Int. 2001 Sep;39(3):199-208
11434978
Electrophoresis. 2006 Nov;27(22):4446-55
17058305
Arch Gen Psychiatry. 2004 Mar;61(3):264-72
14993114
J Chromatogr. 1992 Sep 11;608(1-2):189-95
1430021
CNS Neurol Disord Drug Targets. 2008 Nov;7(5):482-91
19128205
Neurochem Int. 1999 Aug;35(2):153-62
10405999
Addiction. 1998 May;93(5):713-27
9692270
Neuropharmacology. 2004;47 Suppl 1:227-41
15464140
Biochem Pharmacol. 1992 Feb 4;43(3):403-6
1311578
Annu Rev Med. 1998;49:173-84
9509257
Eur J Pharmacol. 1995 Sep 5;283(1-3):151-9
7498304
Int J Neuropsychopharmacol. 2008 May;11(3):425-38
17927843
Physiol Rev. 2009 Apr;89(2):649-705
19342616
Electrophoresis. 2003 Apr;24(7-8):1227-35
12707916