New research suggests a common anti-emetic drug, prochlorperazine, could offer better control for temporal lobe epilepsy. The study found that enhancing the activity of potassium-chloride cotransporter 2 (KCC2) reduced abnormal brain activity and prevented seizures in experimental models.
Temporal lobe epilepsy, particularly its mesial form, is often resistant to standard treatments. Researchers investigated if restoring chloride balance in neurons, a process regulated by KCC2, could suppress the abnormal electrical signaling driving seizures. KCC2 is vital for maintaining the chloride gradient that allows GABA, the brain's main inhibitory neurotransmitter, to dampen neuronal firing.
Two molecules, prochlorperazine and CLP-257, were identified as potential KCC2 enhancers. Laboratory tests showed both compounds increased KCC2 function by promoting its clustering on neuronal membranes. Further analysis indicated CLP-257 strengthened inhibitory signaling.
Experiments using resected brain tissue from patients with drug-resistant epilepsy showed both compounds markedly reduced seizure activity. Similar results were observed in a mouse model, where prochlorperazine or CLP-257 administration significantly decreased seizure frequency.
These findings align with a growing trend of anti-emetic drugs showing anti-epileptic effects, highlighting the potential for repurposing these medications for drug-resistant epilepsy.