Subtype selective kainic acid receptor agonists: discovery and approaches to rational design

TY - JOUR

T1 - Subtype selective kainic acid receptor agonists

T2 - discovery and approaches to rational design

AU - Bunch, Lennart

AU - Krogsgaard-Larsen, Povl

N1 - Keywords: Kainic acid (kainate) receptors; ionotropic glutamate receptors; receptor subtype selectivity; structure-activity-relations; rational drug design

PY - 2009

Y1 - 2009

N2 - (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (mGluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists. In total, over 100 compounds are described by means of chemical structure and available pharmacological data. With this perspective review, it is our intention to ignite and stimulate inspiration for future design and synthesis of novel subtype selective KA receptor agonists.

AB - (S)-Glutamic acid (Glu) is the major excitatory neurotransmitter in the mammalian central nervous system, activating the plethora of glutamate receptors (GluRs). In broad lines, the GluRs are divided into two major classes: the ionotropic Glu receptors (iGluRs) and the metabotropic Glu receptors (mGluRs). Within the iGluRs, five subtypes (KA1, KA2, iGluR5-7) show high affinity and express full agonist activity upon binding of the naturally occurring amino acid kainic acid (KA). Thus these receptors have been named the KA receptors. This review describes all-to our knowledge-published KA receptor agonists. In total, over 100 compounds are described by means of chemical structure and available pharmacological data. With this perspective review, it is our intention to ignite and stimulate inspiration for future design and synthesis of novel subtype selective KA receptor agonists.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1002/med.20133

DO - 10.1002/med.20133

M3 - Review

C2 - 18623169

SN - 0198-6325

VL - 29

SP - 3

EP - 28

JO - Medicinal Research Reviews

JF - Medicinal Research Reviews

IS - 1

ER -