The anticonvulsant action of propofol on epileptiform activity in rat hippocampal slices.
We used extracellular electrophysiological recordings from the CA1 region in rat hippocampal slices to investigate the effects of propofol on the field excitatory postsynaptic potential (fEPSP), population spike, and epileptiform activity induced by a Mg(2+)-free condition. Propofol depressed the population spike, fEPSP, and epileptiform activity. Both aminophylline, a nonselective adenosine receptor antagonist, and 8-cyclopentyl-1,3-dipropylxanthine, an A(1) receptor antagonist, significantly reduced the effect of propofol on fEPSP amplitude. However, 3,7-dimethyl-1-propagylxanthine, an A(2) receptor antagonist, did not alter the effect of propofol on fEPSP amplitude. Picrotoxin, a specific chloride channel blocker, partly reduced the effect of propofol on epileptiform activity, but bicuculline, a competitive gamma-aminobutyric acid(A) receptor antagonist, failed to antagonize it. Aminophylline significantly reduced the action of propofol on the epileptiform activity. The anticonvulsant action of propofol was partly reduced by 8-cyclopentyl-1,3-dipropylxanthine, whereas 3,7-dimethyl-1-propagylxanthine failed to affect it. Adenosine depressed the amplitude of fEPSPs in a dose-dependent manner, and propofol enhanced this inhibition. The results demonstrated that, in rat hippocampal slices, propofol inhibits epileptiform activity. In addition, adenosine neuromodulation through the A(1) receptor may contribute to the anticonvulsant action of propofol.
Ohmori
Hideya
H
*Department of Anesthesiology, Kitami Red Cross Hospital; †Department of Anesthesiology, Moriyama Hospital; and ‡Department of Anesthesiology, Sapporo Medical University School of Medicine, Hokkaido, Japan.
Sato
Yasumitsu
Y
Namiki
Akiyoshi
A
D000241:Adenosine / Q000502:physiology*; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000628:Aminophylline / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants; D001640:Bicuculline / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D015742:Propofol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D000241:Adenosine; D058916:Adenosine A1 Receptor Antagonists; D058917:Adenosine A2 Receptor Antagonists; D000628:Aminophylline; D018686:Anesthetics, Intravenous; D000927:Anticonvulsants; D001640:Bicuculline; D018756:GABA Antagonists; D010726:Phosphodiesterase Inhibitors; D010852:Picrotoxin; D015742:Propofol; D013805:Theobromine; D014970:Xanthines; C067197:8-(dicyclopropylmethyl)-1,3-dipropylxanthine; C057837:3,7-dimethyl-1-propargylxanthine