Overview
- Stummann, T.C. et al. (2005) Eur. J. Pharmacol. 510, 197.
- Veneroni, O. et al. (2003) Pain. 102, 17.
Alomone Labs Ralfinamide mesylate inhibits NaV1.7 channels expressed in HEK293 cells.A: Time course of current reversible inhibition by 100 μM Ralfinamide mesylate (#R-105). Currents were elicited by a voltage ramp from a holding potential of -100 mV to 60 mV (30 ms) delivered every 10 seconds. B: Example traces of current response to voltage ramp stimulation before and during 100 μM Ralfinamide mesylate application.
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 tetrodotoxin1-2. 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 effects4-6.
