Time course of the GABAergic effects of vigabatrin: is the time course of brain GABA related to platelet GABA-transaminase inhibition?
OBJECTIVE
To analyze the time course of the effects of vigabatrin (VGB) on brain gamma-aminobutyric acid (GABA), and its relation with 4-aminobutyrate-2-ketoglutarate amino-transferase (GABA-T) in brain and platelets.


METHODS
Blood and brain samples were collected at 4, 24, 48, and 72 h after a single dose and after 3 and 8 days of treatment with 200 mg/kg of VGB in rats.


RESULTS
Time courses of the GABAergic effects of VGB were different after single and multiple doses: with multiple doses, the inhibition of brain GABA-T was quicker and longer, the inhibition of platelet GABA-T was greater and longer, the increase in brain GABA was greater, and recovery began earlier. After pooling the data obtained at 4, 24, 48, and 72 h, we observed a power correlation between the increase in brain GABA in individual rats as percentage of the control and both the inhibition of brain GABA-T after a single dose of VGB (r = -0.40; p < 0.05), and the inhibition of platelet GABA-T after 3 days (r = -0.48; p < 0.01) and 8 days of treatment (r = -0.53; p < 0.01). When all data after single and multiple doses were pooled, the increase in brain GABA correlated better with the inhibition of GABA-T in platelets (r = -0.62; p < 0.001) than in brain (r = -0.38; p < 0.001). Platelet GABA-T correlated with brain GABA at 4 h (r = -0.64; p < 0.001) and 24 h (r = -0.66; p < 0.001) but not at 48 and 72 h.


CONCLUSIONS
Platelet GABA-T reflects the time course of the increase in brain GABA better than does brain GABA-T after multiple doses of VGB in rats.
Valdizán
E M
EM
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 / Q000037:antagonists & inhibitors* / Q000097:blood; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000097:blood; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood / Q000494:pharmacology
D000927:Anticonvulsants; D005680:gamma-Aminobutyric Acid; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D020888:Vigabatrin