Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats.

摘要

We report the relationship of GABA-transaminase inhibition in platelets and brain with the increase in brain gamma-aminobutyric acid (GABA), as percents of the control, at 24 h after single and after 3 and 8 days of treatment with increasing doses (1, 3, 10, 30, 100 and 300 mg kg(-1) day(-1) of vigabatrin in rats. The inhibition of GABA-transaminase in platelets correlated at least as well as that in brain with the increase in brain GABA after 3 days (r = - 0.87 vs. r = -0.78), and 8 days of treatment (r = -0.77 vs. r = -0.74), and when the data of single and multiple doses were pooled (r = -0.77 vs. r = -0.75). The correlation between platelet GABA-transaminase and brain GABA fitted to a power curve, the increase in brain GABA being significant only when platelet GABA-transaminase was inhibited to less than 50% of the control. Our results suggest that platelet GABA-transaminase could be a peripheral marker of the effect of vigabatrin on brain GABA in rats.