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 investigated the effects of propofol on epileptiform activity in rat hippocampal slices. Interictal epileptiform activity was produced by bath applying one of the following: picrotoxin (PTX; 10 and 50 microM), bicucculine methiodide (BMI; 10 and 50 microM), 4-aminopyridine (4-AP; 50 microM), 8.5 mM [K+]o or 0 [Mg2+]o artificial cerebrospinal fluid. Propofol was then added in increasing concentrations and the effect on the rate 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 microM). Propofol (30 micrograms/ml, 168 microM) completely abolished discharges induced by 8.5 mM [K+]o and at 60 micrograms/ml (337 mM) completely suppressed discharges induced by 4-AP and 0 [Mg2+]o. Propofol was less effective in reducing discharges produced by GABAA/Cl- receptor complex antagonists. Propofol at a concentration of 300 micrograms/ml (1.7 mM) was needed to reduce BMI-induced (50 microM) discharges by 77% and only reduced PTX-induced (50 microM) discharges by 20%. Ictal-like discharges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 micrograms/ml, 16.9-56.2 microM) and the duration of the ictal-like discharge period was significantly reduced. We found that propofol has significant in vitro antiepileptic effects. Additionally, propofol was less effective against GABAA antagonists suggesting that the GABAA receptor complex is the site of its action.
Rasmussen
P A
PA
Department of Neurosurgery, University of Wisconsin Hospital and Clinics, Madison 53792, USA.
Yang
Y
Y
Rutecki
P A
PA
D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D003292:Convulsants; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy*; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010852:Picrotoxin / Q000037:antagonists & inhibitors; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018686:Anesthetics, Intravenous; D000927:Anticonvulsants; D001640:Bicuculline; D003292:Convulsants; D018756:GABA Antagonists; D006993:Hypnotics and Sedatives; D010852:Picrotoxin; D015742:Propofol; C017069:bicuculline methiodide