| 11322931 |
Ambrosio AF, Silva AP, Malva JO, Soares-da-Silva P, Carvalho AP, Carvalho CM: Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivatives of carbamazepine, due to blockade of sodium but not calcium channels. Biochem Pharmacol. 2001 May 15;61(10):1271-5.
We investigated the mechanism (s) of action of two new putative antiepileptic drugs (AEDs), (S)-(-)-10-acetoxy-10,11-dihydro-5H-dibenz [b,f] azepine-5-carboxamide (BIA 2-093) and 10,11-dihydro-10-hydroxyimino-5H-dibenz [b,f] azepine-5-carboxamide (BIA 2-024), by comparing their effects on the release of endogenous glutamate in hippocampal synaptosomes, with those of carbamazepine (CBZ) and oxcarbazepine (OXC). The AEDs inhibited the release of glutamate evoked by 4-aminopyridine (4-AP) or veratridine in a concentration-dependent manner, being CBZ more potent than the other AEDs. Using conditions of stimulation (30 mM KCl), where Na (+) channels are inactivated, the AEDs did not inhibit either the Ca (2+)-dependent or -independent release of glutamate. The results indicate that BIA 2-093 and BIA 2-024 have sodium channel-blocking properties, but CBZ and OXC are more potent than the new AEDs. Moreover, the present data also indicate that Ca (2+) channels coupled to the exocytotic release of glutamate and the activity of the glutamate transporter were not affected by the AEDs. |
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