ADMINISTRATION OF VIGABATRIN (GAMMA-VINYL-GAMMA-AMINOBUTYRIC ACID) AFFECTS THE LEVELS OF BOTH INHIBITORY AND EXCITATORY AMINO-ACIDS IN RAT CEREBROSPINAL-FLUID

Abstract: The effect of vigabatrin (γ‐vinyl‐γ‐aminobutyric acid), a new anticonvulsant drug, on the transmitter amino acids in rat cisternal CSF was studied. CSF was collected through a permanently implanted polyethylene cannula from freely moving rats at 5, 24, 48, and 96 h after administration of 1,000 mg/kg of vigabatrin. The free γ‐aminobutyric acid (GABA) level was elevated maximally (13.5‐fold; p < 0.01) at 24 h after injection, The homocarnosine (GABA‐histidine) level also was increased (123%; p < 0.01) at 24 h after injection, and its concentration remained at the same level for the next 3 days. Glycine and taurine concentrations had increased [31% (p < 0.05) and 63% (p < 0.01), respectively] at 5 h after injection. It is interesting that the levels of glutamate and aspartate increased [330% (p < 0.05) and 421% (p < 0.01), respectively] at 96 h after injection, the time when the free GABA level had returned to the baseline concentration and the vigabatrin level was 3% of the maximal concentration. The present study indicates that a single dose of vigabatrin in rats elevates levels of both the inhibitory and excitatory amino acids in CSF. However, the temporal profile of observed changes in relation to vigabatrin injection shows that neither the long‐lasting elevation of GABA content nor the increase in glutamate and aspartate levels correlates with the level of vigabatrin in CSF. These findings suggest that the excitatory mechanisms are also augmented following acute administration of vigabatrin, especially when the content of GABA had decreased to the baseline level and the level of vigabatrin was low. Copyright © 1990, Wiley Blackwell. All rights reserved