ralfinamide (NW-1029) / Newron - LARVOL DELTA

Sodium Channel Inhibitors in Clinical Development for Pain Management: A Focused Review. (PubMed, CNS Drugs) - "This review explores sodium channel inhibitors currently in clinical development, with a focus on suzetrigine (VX-548), the first US Food and Drug Administration (FDA)-approved Nav1.8 inhibitor for acute pain, as well as other investigational agents such as ralfinamide, OLP-1002, LTGO-33 and HBW-004285. Despite setbacks in early candidates owing to selectivity and tolerability issues, ongoing trials demonstrate renewed optimism for a new class of analgesics that may overcome the limitations of traditional pain therapies. We discuss key pharmacological challenges observed in earlier trials including functional redundancy, species differences, and on-target side effects, and outline how emerging strategies, such as structural biology-guided design, combination therapies, and precision medicine, are paving the way for safer, more effective, nonaddictive pain treatments."

Journal • Review • Addiction (Opioid and Alcohol) • Neuralgia • Pain • NAV1

Inhibition of Nav1.7 channel by a novel blocker QLS-81 for alleviation of neuropathic pain. (PubMed, Acta Pharmacol Sin) - "Ralfinamide has shown anti-nociceptive activity in animal models of inflammatory and neuropathic pain and is currently under phase III clinical trial for neuropathic pain...In addition, QLS-81 (10 μM) did not significantly affect ECG in guinea pig heart ex vivo; and administration of QLS-81 (10, 20 mg/kg, i.p.) in mice had no significant effect on spontaneous locomotor activity. Taken together, our results demonstrate that QLS-81, as a novel Nav1.7 inhibitor, is efficacious on chronic pain in mice, and it may hold developmental potential for pain therapy."

Journal • Neuralgia • Pain • Peripheral Neuropathic Pain

Synthesis and Evaluation of Novel α-Aminoamides Containing Benzoheterocyclic Moiety for the Treatment of Pain. (PubMed, Molecules) - "Compounds 6a, 6e, and 6f containing the benzofuran group displayed more potent in vivo analgesic activity than ralfinamide in both the formalin test and the writhing assay. Interestingly, they also exhibited potent in vitro anti-Na1.7 and anti-Na1.8 activity in the patch-clamp electrophysiology assay. Therefore, compounds 6a, 6e, and 6f, which have inhibitory potency for two pain-related Na targets, could serve as new leads for the development of analgesic medicines."

Journal • Pain