Novel psychotropic agents for the treatment of both negative and positive symptoms of Schizophrenia

The Invention New Chemical Entities (NCE's) psychotropic agents have been developed, possessing anti-dopaminergic activity, along with positive modulatory glutamate NMDA receptor activity. These agents are aimed at the treatment of schizophrenia and bipolar disorder affecting positive symptoms as well as negative symptoms and cognitive deficits, and possibly mood disorders. PGW4, the lead compound, has been assayed both in vitro and in vivo demonstrating anti-psychotic activity and anti-depression and anxiolytic effects along with cognitive improvements The Need Schizophrenia is a chronic, debilitating disease with significant morbidity and mortality, that often requires antipsychotic pharmacotherapy for life. Current therapy consists of neuroleptics of either the atypical or the typical type which share a common anti-dopaminergic activity with no glutamatergic activity. They do not improve the negative symptoms or cognitive deficits. The available anti-psychotics do not interact with the glutamate and GABA systems that were suggested as being involved in the pathophysiology of schizophrenia and bipolar disorder

NMDA-modulatory agents such as D-serine and D-cycloserine (DCS), when used as adjuvant to neuroleptics (e.g. risperidone and olanzapine), showed significant clinical improvement of negative symptoms in schizophrenia However, drugs that penetrate the brain and treat positive, negative and cognitive symptoms of schizophrenia are desperately needed
Advantages A combination of an anti-dopaminergic, anti-serotonergic and positive-modulatorty NMDA-activity antipsychotic drug have the potential to offer a better treatment profile for schizophrenia and related disorders. Due to the efficacy, good tolerability and pharmacological uniqueness, there is a high probability that such agents will be associated with better adherence. Administerd per-os.
Stage PGW4 has been shown to possess: 1) dose-dependent antipsychotic activity (amphetamine and MK-801 models), with minimal sedation and no catalepsy, 2) antidepressant effect at doses which do not induce sedation (forced swim test), and 3) anxiolytic effect (open field model and elevated plus maze model) 4) PGW4 tends to improve cognitive performance, and to antagonize the cognitive deficit induced by MK-801 in the Morris water maze rat model. Additional compounds are currently under in vivo evaluation Patent US 60/854,091 filed on October 2006

Inventor(s): Avraham (Avi) Weizman, Irit Gil-Ad, Moshe Portnoy

Type of Offer: Licensing



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