Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain

Pain. 2003 Mar;102(1-2):17-25. doi: 10.1016/s0304-3959(02)00183-5.

Abstract

NW-1029, a benzylamino propanamide derivative, was selected among several molecules of this chemical class on the basis of its affinity for the [(3)H]batracotoxin ligand displacement of the Na(+) channel complex and also on the basis of its voltage and use-dependent inhibitory action on the Na(+) currents of the rat DRG (dorsal root ganglia) sensory neuron. This study evaluated the analgesic activity of NW-1029 in animal models of inflammatory and neuropathic pain (formalin test in mice, complete Freund's adjuvant and chronic constriction injury in rats) as well as in acute pain test (hot-plate and tail-flick in rats). Orally administered NW-1029 dose-dependently reduced cumulative licking time in the early and late phase of the formalin test (ED(50)=10.1 mg/kg in the late phase). In the CFA model, NW-1029 reversed mechanical allodynia (von Frey test) after both i.p. and p.o. administration (ED(50)=0.57 and 0.53 mg/kg), respectively. Similarly, NW-1029 reversed mechanical allodynia in the CCI model after both i.p. and p.o. administration yielding an ED(50) of 0.89 and 0.67 mg/kg, respectively. No effects were observed in the hot-plate and tail-flick tests up to 30 mg/kg p.o. The compound orally administered (0.1-10 mg/kg) was well tolerated, without signs of neurological impairment up to high doses (ED(50)=470 and 245 mg/kg in rat and mice Rotarod test, respectively). These results indicate that NW-1029 has anti-nociceptive properties in models of inflammatory and neuropathic pain.

Publication types

  • Comparative Study

MeSH terms

  • Amides / administration & dosage
  • Amides / therapeutic use*
  • Animals
  • Ataxia / drug therapy
  • Behavior, Animal / drug effects
  • Chronic Disease / drug therapy
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Evaluation
  • Electroshock / methods
  • Formaldehyde / administration & dosage
  • Freund's Adjuvant / administration & dosage
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Male
  • Mice
  • Motor Activity / drug effects
  • Pain / chemically induced
  • Pain / classification
  • Pain / drug therapy*
  • Pain Measurement
  • Pain Threshold
  • Propionates / administration & dosage
  • Propionates / therapeutic use*
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Sodium Channel Blockers / administration & dosage
  • Sodium Channel Blockers / therapeutic use*

Substances

  • Amides
  • NW 1029
  • Propionates
  • Sodium Channel Blockers
  • Formaldehyde
  • Freund's Adjuvant