PROPOFOL INHIBITS EPILEPTIFORM ACTIVITY IN RAT HIPPOCAMPAL SLICES

Propofol (2,6 di-isopropylphenol) is an intravenous general anesthetic used widely in neuroanesthesia, as a sedative in intensive care units , and has successfully aborted refractory status epilepticus. We inves tigated the effects of propofol on epileptiform activity in rat hippoc ampal slices. Interictal epileptiform activity was produced by bath ap plying one of the following: picrotoxin (PTX; 10 and 50 mu M), bicuccu line methiodide (BMI; 10 and 50 mu M), 4-aminopyridine (4-AP; 50 ELM), 8.5 mM [K+](o) or 0 [Mg2+](o) artificial cerebrospinal fluid. Propofo l was then added in increasing concentrations and the effect on the ra te of extracellular field epileptiform discharges was measured. Ictal- like discharges > 2 Hz for > 2 s) were produced by 7.5 mM [K+](o) and pilocarpine(10 mu M) Propofol(30 mu g/ml, 168 mu M) completely abolish ed discharges induced by 8.5 mM [K+](o) and at 60 mu g/ml (337 mM) com pletely suppressed discharges induced by 4-AP and 0 [Mg2+](o). Propofo l was less effective in reducing discharges produced by GABA(A)/Cl- re ceptor complex antagonists. Propofol at a concentration of 300 mu g/ml (1.7 mM) was needed to reduce BMI-induced (50 mu M) discharges by 77% and only reduced PTX-induced (50 mu M) discharges by 20%. Ictal-like d ischarges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 mu g/ml, 16.9-56.2 mu M) and the duration of the ic tal-like discharge period was significantly reduced. We found that pro pofol has significant in vitro antiepileptic effects. Additionally, pr opofol was less effective against GABA(A) antagonists suggesting that the GABA(A) receptor complex is the site of its action.