Effects of increasing doses of vigabatrin on platelet gamma-aminobutyric acid-transaminase and brain gamma-aminobutyric acid in rats.
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.
Valdizán
E M
EM
Clinical Pharmacology Service, M. de Valdecilla University Hospital, Department of Physiology and Pharmacology, University of Cantabria School of Medicine, Santander, Spain.
García
A P
AP
Armijo
J A
JA
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000201:enzymology*; D001921:Brain / Q000378:metabolism*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
D015415:Biomarkers; D004791:Enzyme Inhibitors; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin