Effects of felbamate on muscarinic and metabotropic-glutamate agonist-mediated responses and magnesium-free or 4-aminopyridine-induced epileptiform activity in guinea pig olfactory cortex neurons in vitro

The effects of the anticonvulsant agent felbamate (FBM) were examined on muscarinic and metabotropic-glutamate receptor agonist-induced responses and chemically induced epileptiform activity, in guinea pig olfactory cortex slices in vitro. FBM (100-500 μM) had little effect on neuronal membrane properties and on postsynaptic potentials evoked by electrical stimulation of lateral olfactory tract terminals, whereas it reduced the duration of presumed Ca ++ spikes induced by intracellular Cs + loading. In contrast, the muscarinic receptor agonist oxotremorine-M (10 μM) or the metabotropic glutamate receptor agonist 1-aminocyclopentane-1S-3R-dicarboxylic acid (10 μM) induced a sustained membrane depolarization with repetitive firing, an increase in input resistance and the appearance of a slow poststimulus afterdepolarizing potential. These effects were reversibly reduced in the presence of FBM (100-500 μM). After preincubation of slices with Mg ++ -free solution or 200 μM 4-aminopyridine, neurons exhibited spontaneous and stimulus-evoked epileptiform potentials that were suppressed by FBM (1 mM). We conclude that FBM can interfere with muscarinic and metabotropic-glutamate response generation and slow afterdepolarization induction in olfactory cortical neurons, most likely by blocking Ca ++ influx through voltage-sensitive Ca ++ channels. A possible interaction of FBM with other voltage-insensitive Ca ++ conductances is also considered. We also suggest that FBM can suppress epileptiform activity induced by Mg ++ -free or 4-aminopyridine exposure primarily through inhibition of N-methyl-o-aspartate-gated ion channels, although additional actions on non-N-methyl-D-aspartate receptor sites and/or presynaptic transmitter release mechanisms cannot be excluded.