TABLE 9.

Equilibrium dissociation constants in micromolar for AMPA receptor competitive antagonists

For all antagonist tables, K_i is the equilibrium dissociation constant calculated from radioligand binding studies, and K_B is the equilibrium dissociation constant calculated from functional assays using either a Schild analysis or a Cheng-Prusoff correction of IC₅₀ values. IC₅₀ values are the concentration of drug required to produce half-maximal inhibition. Data for CNQX and NBQX inhibition of GluA1 or GluA4 coexpressed with GluA2 can be found in Stein et al. (1992).

Antagonist	GluA1	GluA2	GluA3	GluA4
	μM
CNQX	0.6a	0.18b	2.11c
DNQX	0.25d	0.45b	1.66c	0.19–0.49d
NBQX	0.4e	0.59f	0.31–0.63c,f	0.1e
ATPO	38f	65f	110f	150f
YM90K			1.96c
NS102			N.E.c
NS1209	0.12g	0.13g	0.11g	0.06g
Kynurenic acid		1900h
LY293558	9.2i	0.4–3.2i,j	32k	51i
LY377770		>100j
LY382884	N.E.l	N.E.j,l	N.E.l	N.E.l
LY466195	75m	270m N.E.j	312m	432m
UBP296			N.E.n
UBP310		>100o
ACET		>100o

ACET, (S)-1-(2-amino-2-carboxyethyl)-3-(2-carboxy-5-phenylthiophene-3-yl-methyl)-5-methylpyrimidine-2,4-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; YM90K, 6-(1H-imidazol-1-yl)-7-nitro-2,3-(1H,4H)-quinoxalinedione.

^a K_B values are from Schild analysis of responses from rat receptors expressed in X. laevis oocytes and activated by kainate (Dawson et al., 1990).

^b K_i values are for displacing [³H]AMPA binding to BHK cells transfected with GluA2(Q) (Tygesen et al., 1995).

^c K_B values are from the Cheng-Prusoff correction of IC₅₀ values for inhibition of Ca²⁺ influx evoked by 30 μM glutamate in HEK293 cells transfected with human GluA3 (Varney et al., 1998).

^d K_i values are for displacing [3H]AMPA binding to BHK cells transfected with rat cDNA (Andersen et al., 1996).

^e K_B values are from Schild analysis of responses from recombinant receptors expressed in X. laevis oocytes activated by glutamate (Stein et al., 1992).

^f 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).

^g Data for GluA1 and GluA4 are K_i values for displacement of [³H]AMPA from Sf9 cells. GluA4 exhibited low- and high-affinity binding; the high-affinity K_i is reported here. Data for GluA2 and GluA3 are K_B values from the Cheng-Prusoff correction of IC₅₀ values for inhibition of Ca²⁺ influx stimulated by glutamate (250 μM) in HEK293 cells stably expressing GluA2 or GluA3 (Kasper et al., 2006).

^h IC₅₀ values are for inhibition of GluA2 expressed in X. laevis oocytes and activated by 100 μM glutamate (Prescott et al., 2006).

ⁱ K_i values are for displacing [³H]AMPA at human receptors expressed in HEK293 cells (Simmons et al., 1998).

^j K_B values are from the Cheng-Prusoff correction of IC₅₀ values from inhibition of glutamate (200 μM)-evoked Ca²⁺ influx at HEK293 cells expressing GluA2. LY377770 caused a 35% inhibition at 100 μM, whereas LY382884 and LY466195 (called compound 5 in this reference) had no effect at 100 μM (Jones et al., 2006).

^k K_i values are for displacing [³H]AMPA at human GluA3 expressed in HEK293 cells (Bleakman et al., 1999).

^l K_i values are for displacing [³H]AMPA at human receptors expressed in HEK293 cells. N.E. indicates LY382884 displaced less than 30% at 100 μM (Bortolotto et al., 1999).

^m K_i values are for displacing [³H]AMPA at human receptors expressed in HEK293 cells (Weiss et al., 2006).

ⁿ K_B values are from the Cheng-Prusoff corrected IC₅₀ values for inhibition of Ca²⁺ influx evoked by glutamate (100 μM) at human receptors expressed in HEK293 cells (Dolman et al., 2005).

^o IC₅₀ values are for inhibition of Ca²⁺ influx activated by 100 μM glutamate at HEK293 cells expressing human GluA2 (Dolman et al., 2007).