Inhibition of glutamate release by BIA 2-093 and BIA 2-024, two novel derivativ...

• Author(s): Ambrósio, António F. ; Silva, Ana P. ; Malva, João O. ; Soares-da-Silva, Patricio ; Carvalho, Arsélio P. ; Carvalho, Caetana M.
• Date: 2001
• Persistent ID: http://hdl.handle.net/10316/4829
• Origin: Estudo Geral - Universidade de Coimbra
• Subject(s): Antiepileptic drugs; Carbamazepine; Oxcarbazepine; Sodium channels; Calcium channels; Glutamate release
• Document Type: Article
• Language: English

Description

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 Ca2+-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 Ca2+ channels coupled to the exocytotic release of glutamate and the activity of the glutamate transporter were not affected by the AEDs. http://www.sciencedirect.com/science/article/B6T4P-42VM949-B/1/fa9bdc673fba5c5bc75d9e3d94d17f44