Premium
Time Course of the GABAergic Effects of Vigabatrin: Is the Time Course‐of Brain GABA Related to Platelet GABA‐Transaminase Inhibition?
Author(s) -
Valdizán Elsa M.,
García Agueda P.,
Armijo Juan A.
Publication year - 1999
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1157.1999.tb00820.x
Subject(s) - vigabatrin , gabaergic , gaba transaminase , gamma aminobutyric acid , medicine , endocrinology , platelet , gabaa receptor , chemistry , pharmacology , biology , glutamate decarboxylase , anticonvulsant , neuroscience , inhibitory postsynaptic potential , biochemistry , epilepsy , enzyme , receptor
Summary:Purpose: To analyze the time course of the effects of vigabatrin (VGB) on brain γ‐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.