Structure-dependent differences in the effects of the Aconitum alkaloids lappaconitine, N-desacetyllappaconitine and lappaconidine in rat hippocampal slices

Lappaconitine, a C-19 diterpenoid alkaloid from Aconitum sinomontanum has been reported to possess analgesic and antiinflammatory properties in vivo and to inhibit neuronal activity in brain slices. In the present study the effect of lappaconitine has been compared with the effects of its main metabolite N-desacetyllappaconitine and the structurally related alkaloid lappaconidine. For comparison of drug effects population spikes and field excitatory postsynaptic potentials (EPSPs) evoked by stimulation of stratum radiatum or the alveus were studied in normal rat hippocampal slices and in slices treated with low Mg2+-medium. At concentrations of 3-100 mu M, both lappaconitine and N-desacetyllappaconitine inhibited population spikes elicited by stratum radiatum and alvear stimulation as well as the field EPSP recorded in CA1 stratum radiatum. The drug-induced depression of field potential responses was increased with rising stimulus frequency, indicating an activity-dependent mode of action. The effect of N-desacetyllappaconitine on each parameter investigated was significantly stronger than the effect of lappaconitine. Despite the structural relationship, lappaconidine failed to affect neuronal excitability in concentration below 100 mu M, and an increase in stimulus frequency did not potentiate its effect. Moreover, lappaconitine and N-desacetyllappaconitine suppressed epileptiform activity induced by bicuculline or by omission of Mg2+ from the bathing medium. (C) 1997 Elsevier Science B.V.