Effects of the alkaloids 6-benzoylheteratisine and heteratisine on neuronal activity in rat hippocampal slices.
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.
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Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
D000157:Aconitine / Q000031:analogs & derivatives; D000200:Action Potentials / Q000187:drug effects; D000470:Alkaloids / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001640:Bicuculline / Q000633:toxicity; D003292:Convulsants / Q000633:toxicity; D003864:Depression, Chemical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D018756:GABA Antagonists / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects
D000470:Alkaloids; D000700:Analgesics; D003292:Convulsants; D004365:Drugs, Chinese Herbal; D018756:GABA Antagonists; D015222:Sodium Channels; C109503:heteratisine; C104702:6-benzoylheteratisine; D000157:Aconitine; D001640:Bicuculline