[Abstract Title]. - Society for Neuroscience

The therapeutic index, as determined by the rotarod test was within the range of the known anti
epileptics. The onset of action was extremely fast showing its ability to quickly reach the brain.
To explore possible use in psychiatric disorders, NW-3381 was evaluated in the
amphetamine/chlordiazepoxide-induced hyperactivity test, a model of mania in which
lamotrigine and other antiepileptics used in clinical practice for the treatment of bipolar disorders
have been shown to be active. In this test NW-3381 was efficacious at relatively low doses of 5
and 10mg/kg ip (bid) without affecting basal locomotion. Finally, the effects of NW-3381 and
lamotrigine were tested in a pharmacological mouse model of cognitive dysfunctions in
schizophrenia. Both lamotrigine (27 mg/kg ip) and NW-3381 (10mg/kg ip) were active in
preventing the PCP-induced impairment in attentional performance in the 5-choice serial
reaction task.
Taking in account that NW-3381 has low potential for drug-drug interactions as well as low cell
toxicity and fast onset of action, these in vivo data indicate NW-3381 as possible candidate for
epilepsy and psychiatric disorders therapy.
Disclosures: E. Izzo, None; M. Calabresi, None; C. Sabido-David , None; S. Parini, None; A.
Vezzani, None; M. Carli, None; S. Balosso, None; K. Wedzony, None; P. Salvati, None.
Poster
235. Ion Channels in Disease I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 235.7/C53
Topic: B.04.d. Ion channels and disease
Title: Electrophysiological characterization of NW-3381, a potent sodium channel blocker
active in animal models for epilepsy and psychiatric disorders
Authors: L. FARAVELLI, E. COLOMBO, C. SABIDO-DAVID, *P. SALVATI;
Newron Pharmaceuticals SpA, Bresso MI, Italy
Abstract: Sodium channels are involved in the neuronal hyper-excitability that can occur in
pathological conditions such as epilepsy, pain and psychiatric disorders.
Compound NW-3381 was selected from Newron‟ ion channels program, for its high affinity for
sodium channels, good preliminary profile in terms of selectivity and developability and activity
in animal models of epilepsy mania and schizophrenia.
Patch clamp experiments in isolated rat cortical neurons showed that NW-3381 has a selective,
sub-micromolar and voltage dependent inhibition of Na + currents with an apparent affinity for
inactivated channels Ki of 0.2µM. Furthermore, in the same neurons, the sustained repetitive
firing is significantly reduced by NW-3381 in a concentration range of 3-10µM, ten times more