Novel Dopamine D2 Receptor Antagonists and Methods of Their Use

Investigators at the NIH have identified a series of novel, small molecule antagonists of the dopamine D2 receptor. Among the dopamine receptor (DAR) subtypes, D2 DAR is arguably one of the most validated drug targets in neurology and psychiatry. For instance, all receptor-based anti-Parkinsonian drugs work via stimulating the D2 DAR, whereas all FDA approved antipsychotic agents are antagonists of this receptor. Unfortunately, most agents that act as antagonists of D2 DAR are problematic, either they are less efficacious than desired or cause multiple adverse effects. Thus, it is desirable to develop a class of novel therapeutic agents with high selectivity for the D2 DAR. This invention describes dihydrobenzo[b,f][1,4]thiazepine-8-carboxamide compounds, methods of making these compounds, methods of characterizing their in vitro activity, demonstration of in vivo activity in animals, as well as methods of using these compounds to treat central nervous system (CNS) related disorders.

Potential Commercial Applications: Competitive Advantages:
  • Antipsychotic agent
  • Treatment for schizophrenia, Tourette's syndrome, depression
  • Alternative therapy for disorders currently treated with non-selective D2 antagonists
  • Highly selective

Development Stage:
  • In vitro data available
  • In vivo data available (animal)


Juan Marugan (NCATS)  ➽ more inventions...

Jingbo Xiao (NCATS)  ➽ more inventions...

Marc Ferrer-Alegre (NCATS)  ➽ more inventions...

Noel Southall (NCATS)  ➽ more inventions...

David Sibley (NINDS)  ➽ more inventions...

R Benjamin Free (NINDS)  ➽ more inventions...

Intellectual Property:
US Pat: 9,550,742 issued 2017-01-24
US Application No. 61/859,532 filed on 2013-07-29
PCT Application No. PCT/US2014/048619 filed on 2014-07-29

Xiao J, et al. PMID 24666157
Xiao J, et al. PMID 24260782

Collaboration Opportunity:

The National Institute of Neurological Disorders and Stroke is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Novel Dopamine D2 Receptor Antagonists and Methods of Their Use. For collaboration opportunities, please contact Susan Ano at

Licensing Contact:
Susan Ano, Ph.D.
Phone: 301-435-5515

OTT Reference No: E-030-2013-0
Updated: Sep 5, 2017