Differential effect of carbamazepine and oxcarbazepine on excitatory synaptic transmission in rat hippocampus
2008; Wiley; Volume: 62; Issue: 10 Linguagem: Inglês
10.1002/syn.20556
ISSN1098-2396
AutoresMichela Giustizieri, Marta Armogida, Nicola Berretta, Mauro Federici, Silvia Piccirilli, Nicola Biagio Mercuri, Robert Nisticò,
Tópico(s)Ion channel regulation and function
ResumoAbstract In this study, we have compared the effects of two structurally related compounds carbamazepine (CBZ) and oxcarbazepine (OXC), both in current use for the treatment of epilepsy and bipolar disorder, on fast excitatory transmission in rat hippocampal slices. Using electrophysiological recordings, we have investigated the effects of CBZ and OXC on repetitive action potential discharge of CA1 pyramidal neurons demonstrating that both compounds produced firing inhibition with similar IC 50 values. Moreover, we show that bath applied CBZ (0.01–1 mM) exerted a concentration‐dependent decrease in the amplitude of the field excitatory postsynaptic potentials with an IC 50 of ∼194.3 μM. When OXC was used at the same concentrations, the concentration–response curve was shifted to the right (IC 50 of ∼711.07 μM). In addition, we demonstrated that CBZ and OXC reduced, to a different extent, both evoked excitatory postsynaptic currents and NMDA‐, AMPA‐, and KA‐mediated inward currents, CBZ being more potent than OXC. These data highlight distinct presynaptic and postsynaptic sites of action for both compounds and suggest that CBZ, by markedly depressing postsynaptic ionotropic glutamate receptors‐mediated responses, may produce more severe cognitive and memory impairment. Thus, we assume that relatively high doses of OXC could be better tolerated than therapeutically equivalent doses of CBZ, justifying the preferential use of OXC as first‐line treatment in the therapy of neurological and psychiatric disorders, particularly when compared with CBZ. Synapse 62:783–789, 2008. © 2008 Wiley‐Liss, Inc.
Referência(s)