The molecular basis of conantokin antagonism of NMDA receptor function.
The N-methyl-D-aspartate receptor (NMDAR), a subtype of ionotropic glutamate receptor, has been implicated in a host of chronic and acute neurological disorders. Accordingly, much emphasis has been placed on the development of safe and effective therapeutic agents that specifically antagonize this target. The conantokins are a class of small, naturally occurring peptides that inhibit ion flow through the NMDAR. Some conantokins demonstrate receptor subunit selectivity, a pharmacological attribute of emerging importance in the search for suitable drug candidates. The current review summarizes the NMDAR inhibitory properties of the conantokins, including structure-function relationships and mechanism of action. This information is fundamental to the rational design of suitable agents that can effectively treat pathophysiologies linked to NMDAR dysfunction.
Prorok
Mary
M
Department of Chemistry and Biochemistry and the W. M. Keck Center for Transgene Research, University of Notre Dame, Notre Dame, Indiana 46556, USA. mprorok@nd.edu
Castellino
Francis J
FJ
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008978:Mollusk Venoms / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D008978:Mollusk Venoms; D010456:Peptides, Cyclic; D016194:Receptors, N-Methyl-D-Aspartate