LAUSR

The discovery of novel analgesic agents with high potency, low toxicity and low addictive properties remain a priority. This study aims to identify the analgesic potential of quinoline derived α-trifluoromethylated alcohols (QTA) and their mechanism of action. We synthesized and characterized several compounds of QTAs and screened them for antiepileptic and analgesic activity using zebrafish larvae in high thorough-put behavior analyses system. Toxicity and behavioral screening of 9 compounds identified 4 candidates ( C2 , C3 , C7 and C9 ) with antiepileptic properties that induces specific and reversible reduction in photomotor activity. Importantly, C2 and C3 relieves the thermal pain response in zebrafish larvae indicating analgesic property. Further, using novel in vivo CoroNa green assay, we show that C2 and C3 blocks sodium channels and reduces inflammatory sodium signals released by peripheral nerve and tissue damage. Thus, we have identified novel QTA compounds with antiepileptic and analgesic properties which could alleviate neuropathic pain.