Zogenix Announces Presentation of ZX008 Mechanism of Action Data at Annual Meeting of Society of Biological Psychiatry
The assumption to date has been that the anti-seizure activity of fenfluramine is mediated through known, primarily serotonergic mechanisms. However, the meaningful and prolonged reductions in seizure frequency observed following the use of fenfluramine in patients with DS has not been replicated in studies with other serotonergic agents, such as fluoxetine and lorcaserin. These new results exploring mechanism of action demonstrate that fenfluramine, in addition to its serotonergic effects, also exhibits activity at the sigma-1 receptor. Fenfluramine acts as a positive allosteric modulator of the receptor. Recent literature has suggested that activation of the sigma-1 receptor alleviates seizures in validated animal seizure models¹˒². In contrast, lorcaserin displayed no activity at the sigma-1 receptor.
“Collectively, these data support the hypothesis that the unique activity of fenfluramine in Dravet syndrome may be due to both its activity on serotonin receptors and also from its activity as a positive allosteric modulator of the sigma-1 receptor,” said
The title of the poster presentation (Abstract #663) was, "An Examination of the Mechanism of Action of Fenfluramine in Dravet Syndrome: A Look beyond Serotonin".
¹ Vavers et al.,
² Guo et al.,
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