title: Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain.
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.
authors.affiliation: Newron Pharmaceuticals S.p.A Research and Development, Gerenzano, Varese, Italy. orietta.veneroni@newron.it
authors.forename: O
authors.initials: O
authors.lastname: Veneroni
authors.forename: R
authors.initials: R
authors.lastname: Maj
authors.forename: M
authors.initials: M
authors.lastname: Calabresi
authors.forename: L
authors.initials: L
authors.lastname: Faravelli
authors.forename: R G
authors.initials: RG
authors.lastname: Fariello
authors.forename: P
authors.initials: P
authors.lastname: Salvati
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D001259:Ataxia / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004341:Drug Evaluation; D004597:Electroshock / Q000379:methods; D005557:Formaldehyde / Q000008:administration & dosage; D005620:Freund's Adjuvant / Q000008:administration & dosage; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010146:Pain / Q000139:chemically induced / Q000145:classification / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D011422:Propionates / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000577:Amides; C475054:NW 1029; D011422:Propionates; D026941:Sodium Channel Blockers; D005557:Formaldehyde; D005620:Freund's Adjuvant