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.