Influence of pyridoxal 5 '-phosphate alone and in combination with vigabatrin on brain GABA measured by 1H-NMR-spectroscopy

Both iso-forms of the gamma -aminobutyric acid (GABA) synthesising enzyme a nd also the GABA degrading enzyme need pyridoxal 5'-phosphate (PP) as co-en zyme. The aim of the study was to investigate the influence of PP alone and in combination with various doses of vigabatrin (VGB) on brain GABA levels . In eight healthy subjects 300 mg/d PP and various doses of VGB (range, 10 00 mg/d to 4000 mg/d) were given alone or in combination. The GABA+/creatin e (Cr) signals in both occipital lobes were measured before treatment, duri ng monotherapy with PP or VGB, and during combination of both using 1H-NMR- spectroscopy (1H-NMRS). PP alone did not change the GABA+/Cr signals. VGB a lone increased the GABA+/Cr signals in both hemispheres. The combination PP and low-medium dosed VGB (1000-2000 mg/d) did not increase the GABA+/Cr si gnals. The effects of the combination of PP and high dosed (3000-4000 mg/d) VGB on the GABA+/Cr signals varied depending on the sequence of the drugs and dose of VGB. PP alone has no effect on the GABA+/Cr signals in healthy volunteers. The combination of PP and low-high dosed VGB had inconsistent e ffects on the GABA+/Cr signals compared to a VGB monotherapy because PP act ivates also the GABA-degrading enzyme GABA-transaminase. (C) 2001 Elsevier Science Inc.