Anales RANF

S14-01 TARGETING OF ATP-GATED P2 RECEPTORS AS NOVEL TREATMENT FOR DRUG-REFRACTORY EPILEPSY Tobias Engel Royal College of Surgeons in Ireland, Dublin 2, Ireland Epilepsy, a heterogeneous group of neurological syndromes characterized by recurrent seizures, is one of the most common chronic neurological disease affecting ~70 million people worldwide. Despite the progress made in the development of new antiepileptic drugs (AEDs), the biggest challenges that epilepsy presents to drug development have remained unchanged for the last decades: reducing the percentage of patients resistant to all pharmacological interventions and finding a treatment with potential for modifying disease progression. Neuroinflammation is increasingly recognized as one of the key players in seizure generation and in the maintenance of the epileptic phenotype. Consequently, targeting signaling molecules involved in inflammatory processes may represent new avenues to improve treatment in epilepsy. Nucleotides such as adenosine- 5 ′ -triphosphate (ATP) are released in the brain into the extracellular space during pathological conditions such as increased neuronal firing or cell death driving neuroinflammatory processes and neuronal hyperexcitation. Mounting data has demonstrated a causal role for purinergic signaling during epilepsy, in particular for the ATP-gated P2X7 receptor with P2X7 antagonism protecting against acute seizures and potentially providing disease-modifying effects during chronic epilepsy (Jimenez Pacheco et al., J Neurosci. 2016). Emerging evidence is now also suggesting a prominent role for the metabotropic P2Y receptor family during epilepsy; here in particular for the P2Y1 receptor subtype (Alves et al., J Neurosci. 2019) with recent evidence demonstrating potent anticonvulsive and anti-epileptogenic properties of P2Y1 antagonists. In conclusion, P2 receptors may represent potential new targets for seizure control and disease modification.