Effects of carbamazepine and novel 10,11-dihydro-5H-dibenz[b,f]azepine-5-carboxamide derivatives on synaptic transmission in rat hippocampal slices.
The effects of carbamazepine on synaptic transmission in rat hippocampal slices were compared with those of two novel analogues (BIA2-093 and BIA2-024) with equivalent anticonvulsant efficacy but with fewer side effects. Carbamazepine (10-1000 microM) inhibited in a concentration-dependent manner the field excitatory postsynaptic potential (fPSP) response, with an EC50 of 263 microM, and also attenuated the presynaptic volley with a similar EC50 value. Carbamazepine was more potent to inhibit the NMDA receptor component of the fPSP (fPSPNMDA), with an EC50 of 160 microM. BIA2-093 and BIA2-024 were nearly equipotent with carbamazepine to inhibit synaptic transmission, and displayed similar potency to inhibit the fPSP (EC50 of 145 microM and 205 microM) and fPSPNMDA responses (EC50 of 198 microM and 206 microM). As with carbamazepine, BIA2-093 and BIA2-024 also attenuated the presynaptic volley with EC50 values ranging from 142 to 322 microM. These results indicate that carbamazepine and its analogues mostly inhibit synaptic transmission through inhibition of conduction, although carbamazepine, but not BIA2-093 and BIA2-024, may also depress NMDA receptor-mediated responses.
Cunha
Rodrigo A
RA
Laboratory of Neurosciences, Faculty of Medicine, University of Lisbon, Av.Prof.Egas Moniz, 1649-028 Lisboa, Portugal. racunha@clix.pt
Coelho
Joana E
JE
Costenla
Ana Rita
AR
Lopes
Luísa V
LV
Parada
António
A
de Mendonça
Alexandre
A
Sebastião
Ana M
AM
Ribeiro
J A
JA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000927:Anticonvulsants; D002220:Carbamazepine; D003984:Dibenzazepines; D010852:Picrotoxin; D016194:Receptors, N-Methyl-D-Aspartate; C416836:BIA 2-024; C416835:eslicarbazepine acetate