Unveiling the Anti-Seizure Potential of Sigma-1 Receptor Allosteric Modulation

A study was conducted to explore the potential of a new compound, SKF83959, as an anti-seizure agent. The research involved testing this substance in three mouse models to assess its effects on seizures induced by different stimuli. Additionally, the compound's impact on cortical epileptiform activity was measured in rats through electrocorticogram recordings. Another drug, SOMCL-668, a selective modulator of sigma-1 receptors, was also examined for its anti-seizure properties.

The findings indicated that SKF83959 demonstrated anti-seizure capabilities across all mouse models and diminished epileptiform activity in the cortex without affecting spontaneous motor activity or coordination. The effects were negated by a sigma-1 receptor antagonist but were unaffected by a dopamine D1 receptor antagonist. Although SKF83959 did not directly inhibit epileptiform firing in the CA3 neurons, it did enhance the inhibitory effect of another sigma-1 receptor agonist. SOMCL-668, which does not interact with dopamine receptors, showed comparable anti-seizure effects.

The study concludes that both SKF83959 and SOMCL-668 possess anti-seizure activity, suggesting that modulating sigma-1 receptors allosterically could be a promising strategy for developing new treatments for seizure disorders.