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IEC 2025 | Mechanism of action and clinical activity of huperzine A as an anti-seizure medication

Siegward Elsas, MD, Klinik Arlesheim, Arlesheim, Switzerland, comments on the mechanism of action of huperzine A as an anti-seizure medication. Dr Elsas notes that huperzine A has shown promise in various animal models of epilepsy, including genetic models, and has demonstrated a 71.2% reduction in seizure activity in clinical studies. This interview took place at the 36th International Epilepsy Congress (IEC) in Lisbon, Portugal.

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Transcript

I was honored to be invited by Professor Steven Schachter from Harvard University to present his amazing work on huperzine A. This is a novel agent that is extracted from a Chinese type of club moss and has shown a very unusual mechanism of action. It is a highly selective antiacetylcholinesterase inhibitor. And through this, cholinesterase activity is able to activate interneurons which then help to restore the balance between excitation and inhibition, and thereby acting as an anti-seizure effective drug...

I was honored to be invited by Professor Steven Schachter from Harvard University to present his amazing work on huperzine A. This is a novel agent that is extracted from a Chinese type of club moss and has shown a very unusual mechanism of action. It is a highly selective antiacetylcholinesterase inhibitor. And through this, cholinesterase activity is able to activate interneurons which then help to restore the balance between excitation and inhibition, and thereby acting as an anti-seizure effective drug. This is in great contrast to methods of action of all other currently licensed anti-seizure medications, because most of them are suppressant in one way or another by channel blockers or inhibitors of neurotransmitters, whereas this new method of huperzine A actually enhances cognition, whereas there is always some danger of other anti-seizure medications to subtly decrease cognitive action or memory by their inhibitory action on various aspects of neuronal function. It’s fascinating that huperzine A first was found very effective in a lot, almost all animal models of epilepsy. The 6 Hertz model, the pentylenetetrazole model, the kainic acid model, MTLE and NMDA as well as also genetic models of epilepsy like the GAERS rat from Strasbourg, the SCN1A as well as the SCN8A genetic models. And furthermore and even more important there are already clinical studies underway in which it was possible to see a 71.2% reduction of seizure activity over 28 days. So that is highly promising and I look forward to further testing of this plant-derived product in further clinical studies.

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