TABLE 10.

Equilibrium dissociation constants in micromolar for kainate receptor competitive antagonists

Antagonist	GluK1	GluK2	GluK3	GluK1/GluK2	GluK1/GluK5	GluK2/GluK5
	μM
CNQXa	2.6	1.5		1.3	1.6	5.3
DNQX		0.35b
NBQXa	8.0	1.7	3c	6.2	4.2	6.4
ATPO	54d	>340d
NS102		1.4e
NS1209	0.62f	13f
LU97175g	0.088	0.31	0.022
LU115455g	1.3	0.37	0.21
LU136541g	1.1	1.2	0.26
Kynurenic acida	130	33		160	99	N.E.
LY293558a	0.22	N.E.	N.E.	0.65	0.80	N.E.
LY377770a	0.064	N.E.		0.13	0.16	N.E.
LY382884a	0.64	N.E.	N.E.	1.3	0.64	N.E.
LY466195h	0.024	N.E.	8.9	0.024	0.054
UBP296	0.6i	N.E.i	374j	0.8i	1.0i	N.E.i
UBP302k	0.6l	N.E.m	4.0m	0.8l	1.0l	N.E.l
UBP304	0.12n	N.E.n	111o	0.12n	0.18n	N.E.n
UBP310	0.010l	N.E.l	0.023m		0.008l	N.E.l
ACETp	0.007	N.E.	0.092m		0.005	N.E.
2,4-Epi-neoDHq	7.5 (2.4)	74 (7.7)

2,4-Epi-neoDH, 2,4-epi-neodysiherbaine; ACET, (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methyl)-5-methylpyrimidine-2,4-dione; CNQX, 6-cyano-7-nitroquinoxaline-2,3-dione; LU115455, N-(1-(1-carboxymethyl-5,6,7,8-tetrahydro-benzo[f]quinoxaline-2,3-(1H,4H)-dion-9-yl)pyrrol-3-yl)methyl-N0-(4-carboxyphenyl)-urea; LU136541, N′-(4-carboxyphenyl)-N-(1-(1-hydroxy-5,6,7,8-tetrahydrobenzo[f]quinoxaline-2,3-(1H,4H)-dion-9-yl)pyrrol-3-yl)methyl-urea; LU97175, 1-benzamido-7-pyrrol-1-yl-6-trifluoromethylquinoxaline-2,3-(1H,4H)-dione; LY377770, (3S,4aR,6S,8aR)-6-(((1H-tetrazol-5-ylmethyl)oxy)methyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid; N.E., no effect; NS102, 5-nitro-6,7,8,9-tetrahydrobenzo[g]indole-2,3-dione-3-oxime; UBP296, (R,S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl)pyrimidine-2,4-dione; UBP302, 1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl)pyrimidine-2,4-dione; UBP304, 1-(2-amino-2-carboxyethyl)-3-(2-carboxythiophene-3-ylmethyl)pyrimidine-2,4-dione.

^a K_B values for NBQX, CNQX, kynurenic acid, LY293558, LY377770, and LY382884 are calculated using the Cheng-Prusoff correction with the IC₅₀ values reported in Alt et al. (2004).

^b K_i values are for displacing [3H]AMPA binding to BHK cells stably transfected with GluK2 (Tygesen et al., 1995).

^c K_i values are calculated from the Cheng-Prusoff correction using IC₅₀ values for displacement of [³H]kainate in GluK3 receptors expressed in HEK (Löscher et al., 1999).

^d K_B values are from the Cheng-Prusoff correction of IC₅₀ values for inhibition of glutamate-activated Ca²⁺ influx in HEK293 cells stably transfected with rat recombinant receptors (Strange et al., 2006).

^e K_i values are from inhibition of [³H]kainate binding to homomeric GluK2 expressed in HEK293 cells (Verdoorn et al, 1994). In functional studies, however, 10 μM NS102 caused only 50% inhibition of currents evoked from GluK2 by 300 μM glutamate and inhibited GluA2/GluA4 receptors 20%. In functional studies at rat cerebral cortical neurons or dorsal root ganglion neurons, taken to be AMPA receptors and kainate receptors, respectively, NS102 had a K_B of 114 μM and 6 μM, respectively (Wilding and Huettner, 1996).

^f K_i values are for inhibition of [³H]AMPA and [³H]kainate binding at recombinant human GluK1 and GluK2, respectively, expressed in HEK293 cells (Christensen et al., 2004b).

^g K_i for displacement of [³H]kainate to recombinant receptors expressed in HEK293 cells. LU 97175 had a K_i of 1.3 μM and LU 115455 had a K_i of 0.018 μM for displacement of [³H]AMPA at rat brain membranes (Löscher et al., 1999).

^h K_i values are for displacement of [³H]kainate at human receptors expressed in HEK293 cells (Weiss et al., 2006).

ⁱ K_B values are from the Cheng-Prusoff corrected IC₅₀ values for inhibition of Ca²⁺ influx evoked by glutamate (100 μM) at recombinant human receptors expressed in HEK293 cells (More et al., 2004).

^j K_i value are for displacement of [³H]kainate from human GluK3 expressed in HEK293 cells (Dolman et al., 2005).

^k UBP302 is the active enantiomer of UBP296.

^l K_B values are for inhibition of Ca²⁺ influx evoked by glutamate (100 μM) at human recombinant receptors expressed in HEK293 cells (Dolman et al., 2007).

^m IC₅₀ values are for inhibition of currents activated by glutamate (30 mM) at HEK293 cells expressing recombinant receptors (Perrais et al., 2009).

ⁿ K_B values were calculated using the Cheng-Prusoff correction for inhibition of Ca²⁺ influx in HEK293 cells expressing human recombinant receptors (Dolman et al., 2006).

^o K_i values were calculated from displacement of [³H]kainate from human GluK3 expressed in HEK293 cells (Dolman et al., 2006).

^p Data for ACET at GluK1, GluK2, GluK1/GluK5, and GluK2/GluK5 are from Dolman et al. (2007).

^q IC₅₀ values are for inhibition of currents activated by glutamate (10 mM) from HEK293-T/17 cells expressing recombinant receptors (Lash et al., 2008). In the same assay, 300 μM 2,4-epi-neoDH failed to inhibit GluA4 receptors. K_i values for displacement of [³H]kainate from HEK293-T/17 cells expressing recombinant receptors are given in parentheses.