Name: Sandeep Gawaskar
Diploma / M.Sc degree: University of Mumbai, India
(July 2010)

PhD Project: NR2B Selective NMDA Receptor Antagonists

Abstract of Research Project

Among the family of ionotropic glutamate receptors, the NMDA receptor has been of considerable interest for the development of novel therapies for Parkinson’s, Alzheimer’s and Huntington’s disease. The intriguing structural characteristics of the NMDA receptor make it a troublesome as well as a potent site for development of new drugs. Overexcitation of this receptor has been known to be the source of neuronal excitotoxicity as well as some other central nervous system (CNS) disorders. Thus efforts have been invested in developing new antagonists to counter these negative effects.

The NMDA receptor is composed of four subunits. Seven genes for the NMDA receptor subunits have been cloned which are termed as NR1 (eight splice variants from a-h), NR2A-D, NR3A-B. A functional NMDA receptor contains at least one NR1 subunit bearing the glycine binding site and one NR2 subunit bearing the glutamate binding site. Due to the myriad side effects observed with unselective antagonists, subunit selective antagonists are of great interest. Among these due to the restricted expression of the NR2B subunit, antagonists targeting this subunit are of particular interest.

The aim of this work is the design, development and optimization of novel NR2B selective NMDA receptor antagonists. The current project carries forward the work that has already been started in the group. Structural elements of potent lead compounds will be introduced into the benzocycloheptene scaffold. Systematic structural modifications will lead to relationships between the structure and NMDA receptor antagonistic activity.