Anti-allodynic effect of NW-1029, a novel Na(+) channel blocker, in experimental animal models of inflammatory and neuropathic pain.
Pain
; 102(1-2): 17-25, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12620593
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Dor
/
Propionatos
/
Bloqueadores dos Canais de Sódio
/
Amidas
Limite:
Animals
Idioma:
En
Revista:
Pain
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Itália