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Abstract

Abstract: DESCRIPTION: (Adapted From the Applicant's Abstract) Currently available antipsychotics effectively control positive symptoms (hallucinations, delusions), but persistent negative symptoms (withdrawal, apathy) and cognitive deficits are little affected and can be quite disabling in most patients with schizophrenia. Recently, a new class of orally-bioavailable molecule that specifically enhances AMPA-type glutamate receptor activity has been developed. AMPAKINES facilitate acquisition and retention of memory in rodents and humans, and synergistically interact with modern antipsychotics. We recently completed an exploratory safety trial of the AMPAKINE CX516 added to clozapine in 19 treatment-resistant patients. CX516 was well tolerated and produced consistent improvements in negative symptoms, attention, and memory. We now propose to conduct a larger, placebo-controlled trial of CX516 added to olanzapine in patients with schizophrenia. The primary hypothesis is that CX516 will improve negative symptoms, attention, and verbal memory. Secondary aims are: 1) to asses the safety and tolerability of CX516 compared to placebo in olanzapine-treated patients; 2) to assess CX516 effects on positive symptoms, anxiety, depressive symptoms, executive function, and verbal fluency; and 3) to assess effects on extrapyramidal symptoms, including parkinsonism, akathisia and tardive dyskinesia. Positive effects on clinical (negative, positive, extrapyramidal) and neuropsychological (cognition, memory, attention) symptoms in a larger trial will strongly suggest that AMPAKINES may be useful for treatment of schizophrenia. PROPOSED COMMERCIAL APPLICATION: This research may lead to the development of a new, improved class of antipsychotic drug for schizophrenia. These new drugs have the potential to treat the diverse symptoms of this complex disease.

Thesaurus Terms:
AMPA receptor, antipsychotic agent, chemical structure function, combination chemotherapy, drug screening /evaluation, human therapy evaluation, mental disorder chemotherapy, neuropharmacology, schizophrenia, stimulant /agonist
attention, clinical trial, drug interaction, memory, neurotoxicology, oral administration, serotonin inhibitor, verbal behavior
adult human (21+), behavioral /social science research tag, blood test, human subject, neuropsychological test, patient oriented research, psychometrics

Institution:	CORTEX PHARMACEUTICALS, INC.
	15231 BARRANCA PKWY
	IRVINE, CA 92618
Fiscal Year:	2002
Department:
Project Start:	01-FEB-1999
Project End:	31-AUG-2003
ICD:	NATIONAL INSTITUTE OF MENTAL HEALTH
IRG:	ZRG1