BIIR 561 CL is a novel blocker of
AMPA receptors and voltage-dependent
sodium channels. In this study we further describe the effects of
BIIR 561 CL on
AMPA receptor-mediated membrane currents in rodent neurons, as well as in cells expressing recombinant human GluR1/2 receptors in more detail.
BIIR 561 CL suppressed responses to
kainate in neuronal cultures from rat cortex with an IC50 of 9.8 microM. Similar effects were observed using acutely dissociated neurons from the CA1 region of rat hippocampus (IC50 = 9.5 microM). Inhibition of
kainate responses by
BIIR 561 CL was prevented by preapplication of
GYKI 53655, suggesting that both non-competitive inhibitors bind to a common site of the receptor. The effect of 10 microM
BIIR 561 CL on
kainate-induced currents was dependent on extracellular pH, with more pronounced block (84.1%) under acidic conditions (pHextern=6.4), compared to only 30.1% at a pHextern of 8.4. Thus, it can be hypothesized that
BIIR 561 CL inhibits
AMPA receptors in ischaemic brain regions more effectively than in healthy tissue.
BIIR 561 CL inhibited responses to 1 mM
glutamate in cells expressing recombinant human GluR1/2 receptors with similar potency, as compared to
kainate responses in rat neurons (IC50=17.3 microM). The reference compound
NBQX had an IC50 of 25.2 nM. None of the two compounds affected the
glutamate-induced receptor desensitization at any tested concentration. The block by
BIIR 561 CL was not use-dependent and had fast on- and off-kinetics (tauon=6.8 s; tauoff=1.3 s in hGluR1/2 receptors with 30 microM
BIIR 561 CL). Thus,
BIIR 561 CL can be anticipated to have a promising profile for the treatment of
neurological disorders like brain ischaemia and
head trauma.