Medicinal chemistry of competitive kainate receptor antagonists

TY - JOUR

T1 - Medicinal chemistry of competitive kainate receptor antagonists

AU - Larsen, Ann M

AU - Bunch, Lennart

N1 - Keywords: glutamate receptors, kainic acid receptors, competitive antagonists, medicinal chemistry, structure-activity relationship studies

PY - 2011/2/16

Y1 - 2011/2/16

N2 - Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field.

AB - Kainic acid (KA) receptors belong to the group of ionotropic glutamate receptors and are expressed throughout in the central nervous system (CNS). The KA receptors have been shown to be involved in neurophysiological functions such as mossy fiber long-term potentiation (LTP) and synaptic plasticity and are thus potential therapeutic targets in CNS diseases such as schizophrenia, major depression, neuropathic pain and epilepsy. Extensive effort has been made to develop subtype-selective KA receptor antagonists in order to elucidate the physiological function of each of the five subunits known (GluK1-5). However, to date only selective antagonists for the GluK1 subunit have been discovered, which underlines the strong need for continued research in this area. The present review describes the structure-activity relationship and pharmacological profile for 10 chemically distinct classes of KA receptor antagonists comprising, in all, 45 compounds. To the medicinal chemist this information will serve as reference guidance as well as an inspiration for future effort in this field.

KW - Former Faculty of Pharmaceutical Sciences

U2 - 10.1021/cn1001039

DO - 10.1021/cn1001039

M3 - Review

C2 - 22778857

SN - 1948-7193

VL - 2

SP - 60

EP - 74

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

IS - 2

ER -