Novel actions of oxazolidinones: in vitro screening of a triazolyloxazolidinone for anticonvulsant activity

To test the hypothesis that a triazolyloxazolidinone [PH084] has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. Whole-cell synaptic currents, action potentials and extracellular population spikes [PS] were recorded in the cell body area of rat hippocampal CA1 region in acutely prepared slices. Chemical [picrotoxin [100 micro m] and zero magnesium] and electrical seizures were induced and the effect of PH084 [10 micro M] was tested on cellular responses, multiple spikes and spontaneous bursting frequencies. PH084 depressed evoked excitatory postsynaptic currents, action potential firing frequency and PS amplitude. All of these responses did not recover to baseline after 15-20 min washout of PH084. Perfusion with zero magnesium ion [Mg[2+]]-containing buffer converted a single PS to multiple PS [mPS] accompanied by spontaneous burst. PH084 suppressed the mPS and the spontaneous burst frequency and it also suppressed the picrotoxin-induced mPS number. However, it did not affect the frequency of stimulus train-induced after discharge or bursts. Furthermore, 8-10 min pretreatment with PH084 did not affect the ability of zero Mg[2+] buffer, picrotoxin or stimulus train to induce epileptiform activity. Thus, while PH084 may have potential for anticonvulsant activity against chemically induced seizures, it has little or no potential against electrically induced seizures or in preventing epileptiform discharge