6-benzoylheteratisine and Epilepsy

Alkaloids of different Aconitum species are employed as analgesics in traditional Chinese folk medicine. The present study was designed in order to investigate the effects of the structurally related alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampus. Experiments were performed as extracellular recordings of stimulus evoked population spikes in rat hippocampal slices. 6-Benzoylheteratisine (0.01-10 microM) inhibited the ortho- and antidromic population spike as well as the field EPSP in a concentration- and frequency-dependent manner. Heteratisine (1-100 microM) was a less potent inhibitor. It exerted a depression of the orthodromic spike, but failed to affect the antidromic population spike. 6-Benzoylheteratisine (10 microM) diminished epileptiform activity induced by bicuculline. In hippocampal neurons, this compound reduced the peak amplitude of the sodium current. There was no effect of heteratisine on the sodium current in concentrations up to 100 microM. It is concluded that the frequency-dependent action of 6-benzoylheteratisine suggests an inhibition of neuronal activity which underlies epileptiform burst discharges. The predominant effect is a suppression of neuronal activity due to a blockade of sodium channels.

Topics: Aconitine; Action Potentials; Alkaloids; Analgesics; Animals; Bicuculline; Convulsants; Depression, Chemical; Drugs, Chinese Herbal; Epilepsy; GABA Antagonists; Hippocampus; In Vitro Techniques; Male; Neurons; Rats; Rats, Wistar; Sodium Channels

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 microM) evoked a complete suppression of both normal and epileptiform activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) 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.

Topics: Aconitine; Alkaloids; Animals; Bicuculline; Epilepsy; Hippocampus; In Vitro Techniques; Male; Medicine, Chinese Traditional; Plants, Medicinal; Rats; Rats, Wistar

The structurally related Aconitum alkaloids aconitine, lappaconitine, and 6-benzoylheteratisine inhibited the orthodromic and antidromic population spike in hippocampal CA1 area in a frequency-dependent manner. Aconitine (1 microM) completely suppressed epileptiform activity induced by omission of Mg2+ as well as normal neuronal activity, whereas lappaconitine (10 microM) and 6-benzoylheteratisine (10 microM) diminished epileptiform activity by sparing normal neuronal activity.

Topics: Aconitine; Action Potentials; Alkaloids; Animals; Electric Stimulation; Electrophysiology; Epilepsy; Hippocampus; In Vitro Techniques; Magnesium; Neural Inhibition; Neurons; Rats