Table 2

Activity of SIB-1757 and SIB-1893 on recombinant ionotropic glutamate receptors

Receptor SubtypeAgonist Activity (EC50)Antagonist Activity (IC50)
AMPA receptors
 hGluR1i 14.4>30>302.2>30>30
(8.7, 23.9)(2.0, 2.6)
(2.2, 6.5)(1.5, 5.9)
(3.6, 7.7)(0.6, 2.4)
 hGluR3i 26.3>30>302.6>30>30
(18.3, 37.6)(1.9, 3.6)
(12.3, 28.5)(4.0, 5.4)
Kainate receptors
(33.1, 104)(5.2, 35.4)
(5.8, 41.6)(3.7, 16.9)
NMDA receptorsMK-801
(0.26, 1.9)(0.8, 2.1)
(0.26, 0.87)(0.3, 0.8)

Activity of SIB-1757 and SIB-1893 was examined on recombinant glutamate receptors stably expressed in cell lines using Ca2+measurements. For agonist activity determinations (EC50values), SIB-1757 and SIB-1893 were tested alone, and for the antagonist tests (IC50 values), the compounds were tested in the presence of an ∼EC80 value of glutamate. The EC50values for glutamate and the IC50 values for CNQX or MK-801 are reported for each receptor subtype, expressed as the geometric mean (lower, upper S.D.). Data for SIB-1757 and SIB-1893 represent the average of two to four separate determinations.