Bicuculline-Induced Epileptiform Activity in Rat Hippocampal Slices: Suppression by Aconitum Alkaloids

Abstract

Alkaloids of Aconitum spec. (Ranunculaceae) are employed in traditional Chinese folk medicine as analgesics. The present study was designed in order to investigate the effects of the structurally related alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine on experimentally induced epileptiform activity. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. Epileptiform activity was induced by bicuculline. All three alkaloids exerted an inhibitory action on excitability of hippocampal pyramidal cells in a frequency-dependent manner. The onset of inhibition was accelerated by increasing the frequency of electrical stimulation. Aconitine (1 µM) evoked a complete suppression of both normal and epileptiform activity, whereas lappaconitine (10 µM) and 6-benzoylheteratisine (10 µM) selectively diminished the epileptiform afterdischarges and the duration of the bursts, but spared the normal activity. The present findings suggest that the structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine possess an anticonvulsive potential. The predominant effect of these alkaloids is to suppress the spread of seizure activity, and they may therefore tend to distort epileptic events. However, despite their similar structure, they exert qualitatively and quantitatively different inhibitory effects.

key words

Hippocampus - bicuculline - epileptiform activity - Aconitum alkaloids - Ranunculaceae