The DOI matches its Crossref record; 20 of the 20 references it cites were found in a registry or an index.
The novel anticonvulsant MK‐801 binds to the activated state of the N‐methyl‐d‐aspartate receptor in rat brain
Open accessAbstract
The influence of endogenous and exogenous acidic amino acids on the binding of [3 H]‐MK‐801, a selective, non‐competitive antagonist of N‐methyl‐d‐aspartate (NMDA) receptors, has been investigated in rat cerebral cortex crude synaptic membranes (CSM). Removal of endogenous glutamate and aspartate from CSM by repeated washing reduced the affinity of [3 H]‐MK‐801 for its binding site (with no change in the total number of binding sites) and increased NMDA‐sensitive l‐[3 H]‐glutamate binding. In washed CSM, competitive NMDA antagonists of the dl‐α‐amino‐ω‐phosphonocarboxylate series reduced [3 H]‐MK‐801 binding and NMDA‐sensitive L‐[3 H]‐glutamate binding, the most active compounds being 2‐amino‐5‐phosphonovalerate (AP5) and 2‐amino‐7‐phosphono‐heptanoate (AP7). Exogenous excitatory amino acid agonists enhanced the binding of [3 H]‐MK‐801 to washed CSM by up to 700%. A selective involvement of NMDA receptors in these effects was indicated by the excellent correlation between EC 50 s for stimulation of [3 H]‐MK‐801 binding and IC 50 s for inhibition of NMDA‐sensitive l‐[3 H]‐glutamate binding in the same membranes. The selective, competitive NMDA receptor antagonist D‐AP5 blocked the l‐glutamate‐induced increase in [3 H]‐MK‐801 binding in a competitive manner with a pA 2 value of 6.0. These results seem to reflect a molecular interaction between two distinct components of the NMDA receptor complex: the transmitter recognition site and the site through which MK‐801 exerts its antagonist effects, possibly the ion channel.
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Excitatory Amino Acid Transmitters
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The anticonvulsant MK-801 is a potent N-methyl-D-aspartate antagonist.
Wong, E. H., Kemp, J. A., Priestley, T., Knight, A. R., Woodruff, G. N., & Iversen, L. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.18.7104 · Cited by 1,819
Self-citationFoster, A. C., & Fagg, G. E. (1984) · Brain Research Reviews · doi:10.1016/0165-0173(84)90020-1 · Cited by 818
Self-citationDRUG INTERACTIONS AT THE GABA RECEPTOR-IONOPHORE COMPLEX
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Huettner, J. E., & Bean, B. P. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.4.1307 · Cited by 751
Danysz, W., & Parsons, C. G. (1998) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01382-6 · Cited by 649
Developmental switch in the expression of NMDA receptors occurs in vivo and in vitro
Williams, K., Russell, S. L., Shen, Y. M., & Molinoff, P. B. (1993) · Neuron · doi:10.1016/0896-6273(93)90317-k · Cited by 455
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Metadata
- Authors
- Foster, A. C., & Wong, E. H. F.
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1987-06
- Volume
- 91
- Issue
- 2
- Pages
- 403-409
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- OpenAlex
- W2048152070
- Cited by
- 448
- References
- 20
- FWCI
- 17.82
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Foster, A. C., & Wong, E. H. F. (1987). The novel anticonvulsant MK‐801 binds to the activated state of the N‐methyl‐d‐aspartate receptor in rat brain. British Journal of Pharmacology. https://doi.org/10.1111/j.1476-5381.1987.tb10295.x
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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