alexa The effects of Aconitum alkaloids on the central nervous system.
Immunology

Immunology

International Journal of Inflammation, Cancer and Integrative Therapy

Author(s): Ameri A

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Abstract Preparations of Aconitum roots are employed in Chinese and Japanese medicine for analgesic, antirheumatic and neurological indications. The recent surge in use of phytomedicine derived from traditional Chinese medicine as well as increasing concerns about possible toxic effects of these compounds have inspired a great deal of research into the mechanisms by which certain Aconitum alkaloids may act on the central nervous system. The pharmacological effects of preparations of Aconitum roots are attributed to several diterpenoid alkaloids. The main alkaloid of these plants is aconitine, a highly toxic diterpenoid alkaloid which is known to suppress the inactivation of voltage-dependent Na+ channels by binding to neurotoxin binding site 2 of the alpha-subunit of the channel protein. In this article the pharmacology of several structurally related Aconitum alkaloids is highlighted and their therapeutic vs toxic potential is discussed. Neurochemical and neurophysiological studies will be 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 activity. Considering the chemical structure of the Aconitum alkaloids as well as their mechanism of action, a subdivision in three groups becomes obvious: the first group comprises such alkaloids which possess high toxicity due to two ester boundings at the diterpene skeleton. The members of this group activate voltage-dependent sodium channels already at resting potential and inhibit noradrenaline reuptake. Activation of sodium channels and in consequence excessive depolarization with final inexcitability and suppression of pain transmission account for their antinociceptive properties. The second group comprises less toxic monoesters which have been shown to possess strong antinociceptive, antiarrhythmic and antiepileptiform properties due to a blockade of the voltage-dependent sodium channel. Electrophysiological studies have revealed a use-dependent inhibition of neuronal activity by these alkaloids. They seem to be competitive antagonists of the group I-alkaloids. The third group of Aconitum alkaloids are lacking an ester side chain in the molecule. Toxicity is markedly reduced when compared with the two other groups. They fail to affect neuronal activity, but are reported to have antiarrhythmic actions suggesting that they may have different affinities to various subtypes of the alpha-subunit of the Na+ channel in brain and heart.
This article was published in Prog Neurobiol and referenced in International Journal of Inflammation, Cancer and Integrative Therapy

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