[Abstract Title]. - Society for Neuroscience

Incubation of rat cortical neurons for 24 h at 37°C in a serumless medium containing veratridine
(30 κM) resulted in a significant increase in cell death. NW-3381, added 1 h before veratridine,
was able to reduce the neuronal damage with an IC50 = 6 κM.
Our results show that NW-3381 by functionally blocking the consequences of Na + channel
activation (both the Na + influx and the subsequent Ca 2+ influx due to the prolonged
depolarization) might have a potential for neuroprotection.
Disclosures: P. Salvati, None; L. Curatolo, None; A. Restivo, None; C. Sabido-david,
None; S. Francisconi, None; C. Caccia, None.
Poster
235. Ion Channels in Disease I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 235.6/C52
Topic: B.04.d. Ion channels and disease
Support: 6TH FRAMEWORK EUROPEAN PROGRAM
Title: Antiepileptic properties and antipsychotic potential of NW-3381, a novel potent sodium
channel blocker
Authors: E. IZZO 1 , M. CALABRESI 1 , *C. SABIDO-DAVID 1 , S. PARINI 1 , A. VEZZANI 2 , M.
CARLI 2 , S. BALOSSO 2 , K. WEDZONY 3 , P. SALVATI 1 ;
1 Newron Pharmaceut SPA, Bresso, Italy; 2 MARIO NEGRI INSTITUTE, MILANO, Italy;
3 Polish Acad. of Sci., KRAKOW, Poland
Abstract: Sodium channels have been implicated in a number of diseases including epilepsy,
pain and psychiatric disorders. Several drugs in the market targeting sodium channels have
shown to be effective against these diseases. NW-3381 was selected for its high potency (submicromolar
range) for the target (sodium channels) and good preliminary profile in terms of
selectivity and developability.
To assess its antiepileptic activity, NW-3381 was tested in a range of seizure models in mice: the
maximal electroshock test (MES), the kainic acid (KA)-induced status epilepticus (SE), and the
ip pentylenetetrazol (PTZ)-induced generalized seizures, in comparison to the antiepileptic drug
lamotrigine. In the MES test the compound resulted to be active both after intraperitoneal (ip)
and oral (po) treatment with ED50 of 4.6mg/kg and 8.9mg/kg respectively. In the KA model the
dose of 20mg/kg po significantly inhibited seizure generalization and the incidence of SE while
lamotrigine at 30mg/kg ip was ineffective. In the PTZ model NW-3381 20mg/kg ip protected
from generalized seizure whereas lamotrigine at 15 and 30mg/kg ip worsened seizure severity.