Ralfinamide mesylate

Voltage-gated Na⁺ channels (VGSCs) comprise a large multi-gene family encoding individual subtypes that can be differentiated on the basis of primary structure, biophysical properties and sensitivity to the neurotoxin tetrodotoxin^1-2. Most VGSCs, termed TTX-sensitive (TTXs), have been both found in brain and sensory neurons where they have a low threshold for activation and rapid inactivation kinetics; by contrast other VGSCs are termed TTX-resistant (TTXr). These may play a key role in persistent pain states, including neuropathic and chronic inflammatory pain.

Ralfinamide mesylate (NW-1029) is a Na⁺ channel blocker that suppresses tetrodotoxin (TTX)-resistant Na⁺ currents in small to medium size (C-type) dorsal root ganglia (DRG) neurons about twice as selectively as it blocks TTX-sensitive currents in the same neurons; IC₅₀ values for tonic block of half-maximal inactivated tetrodotoxin-resistant and tetrodotoxin-sensitive currents are 10 μM and 22 μM, respectively³. The blocking action of ralfinamide shows frequency and voltage dependence³. In experimental animal models of inflammatory and neuropathic pain, systemic administration of ralfinamide elicits anti-nociceptive effects^4-6.