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 Applications

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
2R44MH059450-02A1
Application #
6344036
Study Section
Special Emphasis Panel (ZRG1-BDCN-1 (02))
Program Officer
Light, Enid
Project Start
1999-02-01
Project End
2003-08-31
Budget Start
2001-09-25
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$436,284
Indirect Cost
Name
Cortex Pharmaceuticals, Inc.
Department
Type
DUNS #
City
Irvine
State
CA
Country
United States
Zip Code
92618
Mamtani, Manju; Kulkarni, Hemant; Dyer, Thomas D et al. (2013) Waist circumference independently associates with the risk of insulin resistance and type 2 diabetes in mexican american families. PLoS One 8:e59153
Kulkarni, Hemant; Meikle, Peter J; Mamtani, Manju et al. (2013) Plasma lipidomic profile signature of hypertension in Mexican American families: specific role of diacylglycerols. Hypertension 62:621-6