Novel Actions of Oxazolidinones: In vitro Screening of a Triazolyloxazolidinone for Anticonvulsant Activity

Abstract

Objective: To test the hypothesis that a triazolyloxazolidinone (PH084) has anticonvulsant activity by examining its effects on in vitro seizure models in the rat hippocampus. Materials and Methods: 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 µ<smlcap>M</smlcap>) and zero magnesium] and electrical seizures were induced and the effect of PH084 (10 µ<smlcap>M</smlcap>) was tested on cellular responses, multiple spikes and spontaneous bursting frequencies. Results: 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 (Mg²⁺)-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 Mg²⁺ buffer, picrotoxin or stimulus train to induce epileptiform activity. Conclusions: 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.