In:
Journal of Neurochemistry, Wiley, Vol. 71, No. 1 ( 1998-07), p. 418-426
Abstract:
Abstract: A new AMPA receptor antagonist, Ro 48‐8587, was characterized pharmacologically in vitro. It is highly potent and selective for AMPA receptors as shown by its effects on [ 3 H]AMPA, [ 3 H]kainate, and [ 3 H]MK‐801 binding to rat brain membranes and on AMPA‐ or NMDA‐induced depolarization in rat cortical wedges. [ 3 H]Ro 48‐8587 bound with a high affinity ( K D = 3 n M ) to a single population of binding sites with a B max of 1 pmol/mg of protein in rat whole brain membranes. [ 3 H]Ro 48‐8587 binding to rat whole brain membranes was inhibited by several compounds with the following rank order of potency: Ro 48‐8587 〉 6‐nitro‐7‐sulphamoylbenzo[ f ]quinoxaline‐2,3‐dione (NBQX) 〉 YM 90K 〉 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX) 〉 quisqualate 〉 AMPA 〉 glutamate 〉 kainate 〉 NMDA. The distribution and abundance of specific binding sites (∼95% of total) in sections of rat CNS, revealed by quantitative receptor radioautography and image analysis, indicated a very discrete localization. Highest binding values were observed in cortical layers (binding in layers 1 and 2 〉 binding in layers 3–6), hippocampal formation, striatum, dorsal septum, reticular thalamic nucleus, cerebellar molecular layer, and spinal cord dorsal horn. At 1 n M , the values for specific binding were highest in the cortical layers 1 and 2 and lowest in the brainstem (∼2.6 and 0.4 pmol/mg of protein, respectively). Ro 48‐8587 is a potent and selective AMPA receptor antagonist with improved binding characteristics (higher affinity, selectivity, and specific binding) compared with those previously reported.
Type of Medium:
Online Resource
ISSN:
0022-3042
,
1471-4159
DOI:
10.1046/j.1471-4159.1998.71010418.x
Language:
English
Publisher:
Wiley
Publication Date:
1998
detail.hit.zdb_id:
80158-6
detail.hit.zdb_id:
2020528-4
SSG:
12
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