Inhibition of stimulus-triggered and spontaneous epileptiform activity in rat hippocampal slices by the Aconitum alkaloid mesaconitine.
The aim of the present study was to investigate if the plant alkaloid, mesaconitine, which has been reported to have antinociceptive effects via stimulation of the noradrenergic system, inhibits epileptiform field potentials. The experiments were performed as extracellular recordings on rat hippocampal slices. Epileptiform activity was induced by omission of Mg2+ from the bathing medium or by addition of bicuculline and stimulus-evoked population bursts were recorded in the CA1 region. Spontaneous epileptiform activity was elicited by perfusing a nominally Mg2+-free bathing medium with high K+ concentration (5 mM). Both stimulus-triggered and spontaneous epileptiform activity was attenuated in a concentration-dependent manner by mesaconitine (30 nM-1 microM). The inhibitory effect was rather variable in appearance when lower concentrations (30 and 100 nM) of mesaconitine were applied. Pretreatment of the slices with the alpha-adrenoceptor antagonist yohimbine (1 microM) prevented the effect of mesaconitine. It is concluded that the inhibitory action of mesaconitine at low concentration is mediated via alpha-adrenoceptors.
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Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
D000157:Aconitine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology* / Q000517:prevention & control*; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000503:physiopathology*; D066298:In Vitro Techniques; D008274:Magnesium / Q000502:physiology; D008297:Male; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013999:Timolol / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000927:Anticonvulsants; D018756:GABA Antagonists; D015016:Yohimbine; C019470:mesaconitine; D011189:Potassium Chloride; D013999:Timolol; D008274:Magnesium; D000157:Aconitine; D001640:Bicuculline