E M Valdizán1, A P García, J A Armijo. 1. M. de Valdecilla University Hospital, Department of Physiology and Pharmacology, University of Cantabria School of Medicine, Santander, Spain.
Abstract
PURPOSE: 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.
PURPOSE: 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.