Structure-dependent inhibitory action of the Aconitum alkaloids 14-benzoyltalitasamine and talitasamine in rat hippocampal slices

Abstract

In the present study the effects of the two Aconitum alkaloids 14-benzoyltalitasamine and talitasamine on neuronal activity were investigated in order to obtain further insight into structure-dependent effects of this group of alkaloids on central nervous activity. Both alkaloids are closely related to aconitine, the main alkaloid of plants of Aconitum species. However, they have shortened side chains at position C3 and C8 of the molecule. The experiments were performed as extracellular recordings of orthodromically and antidromically evoked population spikes as well as of field excitatory potentials (EPSPs) from the CA1 region of rat hippocampal slices. 14-Benzoyltalitasamine exerted a reversible inhibition of the field potentials in a concentration-dependent manner. The orthodromic population spike was attenuated at concentrations higher than 1 microM, while the field EPSP was already affected at a concentration of at least 0.3 microM. Both responses were completely blocked at a concentration of 30 microM. The alkaloid failed to affect the presynaptic fiber spike at concentrations less than 10 microM. There was only a up to 30% decrease in the antidromic population spike (10-100 microM). The inhibition of the antidromic spike was increased by using a higher stimulus frequency. In contrast to 14-benzoyltalitasamine, the alkaloid talitasamine which is lacking the benzoylester side chain was a less effective inhibitor of the orthodromic population spike and even failed to affect the antidromic spike. Furthermore, the effects of the alkaloids on experimentally induced epileptiform activity was examined. While talitasamine was lacking any significant effect at concentrations less than 100 microM, 14-benzoyltalitasamine reversibly reduced both stimulus-triggered epileptiform activity in area CA1 elicited by omission of Mg2+ from the bathing medium as well as spontaneously occurring epileptiform activity in CA3 elicited by omission of Mg2+ and elevation of K+ to 5 or 8 mM. The antiepileptiform efficacy of this compound was concentration-dependent (0.3-10 microM) and manifested itself as a decrease in burst frequency as well as in burst amplitude and was significantly increased by the higher K+ concentration.

Aconitum in Traditional Chinese Medicine—A valuable drug or an unpredictable risk?

“…3. DDA reduction during processing of aconite roots by pressure-steaming technique and that they should not be entirely diminished from the drug (Ameri, 1998b;Yang et al, 1997).…”

“…Independent of the processing way chosen for herbal preparations, decomposition of DDAs should be achieved. Nevertheless, an appropriate minimal DDA content is still required to achieve its pharmacological effects while reducing its high toxicity (Ameri, 1998b;Yang et al, 1997).…”

“…Neurochemical and neurophysiological studies were reviewed with emphasis on the effects of the alkaloids in regions of the brain that have been implicated in pain transmission and generation of epileptic convulsions. The results indicated that 6-benzoylhetereatisine, MA and LA might inhibit experimentally induced epilepsy (Ameri, 1998b).…”

A review on phytochemistry, pharmacology and toxicology studies of Aconitum

“…Anti‐epileptic studies revealed that the presence of an aromatic substituent is essential for anti‐epileptic activity. Aconitum compounds with aromatic substituent 6‐benzoylheteratisine, 1‐benzoylnapelline, lappaconitine and 14 benzoyltalatisamine inhibited rat hippocampal excitability more potently than heteratisine, napelline, lappaconidine and talatisamine, respectively [70–73]…”

Circadian aspects of hyperthermia in mice induced by Aconitum napellus

“…[1] The precise neurophysiologic mechanism of Acn action is not completely known, but its main and most toxic component, aconitine, which is characterized by a steroidal alkaloid chemical structure, has been studied in the central nervous system of rats at the level of the hippocampus neuronal activity. [46] Specialized neurophysiological research, based on patch-clamp techniques mainly related to the neuron excitability process, has demonstrated that a low physiological Acn dose (10 −6 M) affects individual pre-synaptic rat neuron excitability by opening Na+ channels. [47]…”