Inhibition of rat hippocampal excitability by the Aconitum alkaloid, 1-benzoylnapelline, but not by napelline.
The effects of the two structurally related Aconitum alkaloids, 1-benzoylnapelline and napelline, were investigated by extracellular recording of the stimulus-evoked population spike in the CA1 region of rat hippocampal slices in vitro. 1-Benzoylnapelline (1-100 microM) exerted a depressant action on the orthodromic as well as on the antidromic population spike. Napelline failed to evoke a significant effect at concentrations up to 100 microM. The inhibitory action induced by 1-benzoylnapelline was enhanced when the frequency of electrical stimulation was increased. In contrast, reversal of the inhibitory effect was accelerated when stimulation frequency was decreased. The activity-dependent mode of action of 1-benzoylnapelline raised the question of whether the drug is effective to suppress epileptiform activity. The results obtained from experiments on epileptiform hippocampal slices revealed a reduction of the burst duration and of the number of spikes in the burst as well as attenuation of the amplitude of the population spikes. These data support the conclusion that 1-benzoylnapelline, in contrast to the structurally related compound, napelline, has an activity-dependent inhibitory action on central neurons.
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Department of Pharmacy and Pharmacology of Natural Compounds, University of Ulm, Germany.
D000157:Aconitine; D031841:Aconitum / Q000031:analogs & derivatives* / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004558:Electric Stimulation; D004827:Epilepsy / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
C109327:1-benzoylnapelline; D004365:Drugs, Chinese Herbal; C109326:napelline; D000157:Aconitine