Principal Investigators
David I. Schuster Ph.D., Department of Chemistry
Randall B. Murphy Ph.D. Department of Chemistry and Center for Neural Sciences
Faculty of Arts and Sciences, New York University

The clinical efficacy of classical antipsychotic (neuroleptic) agents has been attributed to their ability to act as an antagonist at postsynaptic dopamine D-2 receptor sites in the brain. However, long term treatment with these agents is associated with a finite risk of tardive dyskinesia which can be irreversible. Therefore, there is a pressing need for drugs which produce neuroleptic effects by interaction at neuroreceptor sites other than at postsynaptic D-2 receptors. Recently, several compounds have been discovered which act as neuroleptic (antipsychotic) agents and have much higher affinity for a class of neuroreceptor sites known as sigma sites, than for dopamine sites. Several investigators have concluded that the sigma receptor/binding site (SRBS) is biologically significant and is involved a modulatory role in mesolimbic dopaminergic function. The pharmacology of the SRBS is complex and the structural diversity of compounds which bind to SRBS is very great.

Description of the Project
Dr. Schuster and Dr. Murphy have synthesized and begun characterizing a novel class of rigid heterocyclic compounds which are close structural analogues of compounds which have high potency at SRBS. It is important to note that each member of this novel class of compounds has several stereoisomers. This feature enables greater structural control of neuroreceptor specificity and suggests the novel compounds have greater therapeutic potential than that of other known neuroreceptor ligands.

Initial screening studies show the novel compounds have binding specificities similar to that of the atypical neuroleptic clozapine. In addition to binding to sigma receptors they also bind to serotonin (5HT2) and dopamine (D2) receptors, properties thought to be important in determining the atypicality of neuroleptics in general and clozapine in particular.

Applications
The novel compounds have potential as a new class of neuroleptics devoid of extra-pyramidal side effects, and as agents for the treatment of schizoaffective and panic disorders, and related syndromes.

NYU is seeking an industrial partner to assist in the further development and commercialization of this novel class of neuroleptic compounds.

Patent Status
A patent for this technology has recently issued in the United States.

For further information please contact:
Larry Schlossman
larry.schlossman@med.nyu.edu
New York University
Office of Industrial Liaison
650 First Avenue, New York, N.Y. 10016
Tel: (212) 263-8178 Fax: (212) 263-8189