CHARACTERIZATION OF KAINATE & AMPA RECEPTOR ANTAGONIST

STROKE IS THE MOST PROMINENT CNS DISORDER IN THE UNITED STATES AS WELL AS THE LEADING CAUSE OF DISABILITY AND THE THIRD LEADING CAUSE OF DEATH. HOWEVER, THERE ARE NO EFFECTIVE TREATMENTS AVAILABLE TO PREVENT OR REDUCE NEURONAL DAMAGE RESULTING FROM STROKE OR OTHER FORMS OF CEREBRAL ISCHEMIA. EPILEPSY IS THE SECOND MOST PROMINENT CNS DISORDER, YET DESPITE THE WIDESPREAD AVAILABILITY OF EFFECTIVE ANTICONVULSANTS A LARGE PORTION OF THE PATIENT POPULATION STILL SUFFERS FROM INTRACTABLE SEIZURES. THEREFORE, THE DEVELOPMENT OF CEREBROPROTECTIVE AND NOVEL ANTICONVULSANT AGENTS IS URGENTLY NEEDED. A GROWING BODY OF EVIDENCE SUGGESTS THAT PHARMACOLOGICAL BLOCKADE OF NON-NMDA GLUTAMATE RECEPTORS, PRINCIPALLY KAINATE AND AMPA RECEPTORS, COULD PROVIDE SIGNIFICANT THERAPEUTIC BENEFIT IN THE TREATMENT OF SEIZURE DISORDERS AND THE PREVENTION OF NEURONAL DAMAGE AND DEATH. NOVA HAS IDENTIFIED PROPRIETARY COMPOUNDS POSSESSING KAINATE/AMPA RECEPTOR ANTAGONIST PROPERTIES AND HAS A MEDICINAL CHEMISTRYEFFORT DEVOTED TO THE SYNTHESIS OF NEWER COMPOUNDS. THE PRIMARY GOAL OF THE PHASE I PROJECT IS TO FURTHER CHARACTERIZE THESE COMPOUNDS AND WILL BE ACCOMPLISHED BY COMBINING IN VITRO ELECTROPHYSIOLOGY AND MOLECULAR BIOLOGY APPROACHES WITH IN VIVO BEHAVIORAL STUDIES. THE PURPOSE OF THESE STUDIES IS TO ASSESS THE THERAPEUTIC POTENTIAL OF NOVA'S KA/AMPA RECEPTOR ANTAGONISTS AS ANTICONVULSANT AND CEREBROPROTECTIVE AGENTS. STROKE IS THE MOST PROMINENT CNS DISORDER IN THE UNITED STATES AS WELL AS THE LEADING CAUSE OF DISABILITY AND THE THIRD LEADING CAUSE OF DEATH. HOWEVER, THERE ARE NO EFFECTIVE TREATMENTS AVAILABLE TO PREVENT OR REDUCE NEURONAL DAMAGE RESULTING FROM STROKE OR OTHER FORMS OF CEREBRAL ISCHEMIA. EPILEPSY IS THE SECOND MOST PROMINENT CNS DISORDER, YET DESPITE THE WIDESPREAD AVAILABILITY OF EFFECTIVE ANTICONVULSANTS A LARGE PORTION OF THE PATIENT POPULATION STILL SUFFERS FROM INTRACTABLE SEIZURES. THEREFORE, THE DEVELOPMENT OF CEREBROPROTECTIVE AND NOVEL ANTICONVULSANT AGENTS IS URGENTLY NEEDED. A GROWING BODY OF EVIDENCE SUGGESTS THAT PHARMACOLOGICAL BLOCKADE OF NON-NMDA GLUTAMATE RECEPTORS, PRINCIPALLY KAINATE AND AMPA RECEPTORS, COULD PROVIDE SIGNIFICANT THERAPEUTIC BENEFIT IN THE TREATMENT OF SEIZURE DISORDERS AND THE PREVENTION OF NEURONAL DAMAGE AND DEATH. NOVA HAS IDENTIFIED PROPRIETARY COMPOUNDS POSSESSING KAINATE/AMPA RECEPTOR ANTAGONIST PROPERTIES AND HAS A MEDICINAL CHEMISTRYEFFORT DEVOTED TO THE SYNTHESIS OF NEWER COMPOUNDS. THE PRIMARY GOAL OF THE PHASE I PROJECT IS TO FURTHER CHARACTERIZE THESE COMPOUNDS AND WILL BE ACCOMPLISHED BY COMBINING IN VITRO ELECTROPHYSIOLOGY AND MOLECULAR BIOLOGY APPROACHES WITH IN VIVO BEHAVIORAL STUDIES. THE PURPOSE OF THESE STUDIES IS TO ASSESS THE THERAPEUTIC POTENTIAL OF NOVA'S KA/AMPA RECEPTOR ANTAGONISTS AS ANTICONVULSANT AND CEREBROPROTECTIVE AGENTS.