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NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology.
J Pharmacol Exp Ther. 1997 Feb; 280(2):614-20.JP

Abstract

The potencies of various N-methyl-D-aspartate(NMDA) receptor channel blockers were determined at recombinant NMDA receptors containing differing combinations of NR1 and NR2 subunits expressed in Xenopus laevis oocytes. When the NR1 subunit was varied (NR1e/NR2A or NR1b/NR2A), none of the 9 channel blockers tested displayed a statistically different affinity. In contrast, altering NR2 composition changed the affinities of several channel blockers. Three of 10 compounds displayed significantly higher affinities for NR1b/NR2C receptors than NR1b/NR2A receptors, and three of five compounds had higher affinity at NR1b/NR2C than NR1b/NR2B receptors. Both MK-801 and N-[1-(2-thienyl)cyclohyxyl]piperidine displayed identical affinities at all receptor subunit combinations tested. However, these two compounds displayed significantly slower rates of blockade and unblockade at NR1b/NR2C than at NR1b/NR2A receptors, perhaps reflecting the shorter mean open times of NR1/NR2C receptors. NR1b/NR2B and NR1b/NR2A were distinguished by one of five compounds tested. Taken together, these results indicate that NR2 subunits impart differing pharmacological profiles to NMDA receptors; thus, it may be possible to develop NMDA receptor channel blocker antagonists of greater subtype selectivity.

Authors+Show Affiliations

Department of Pharmacology, University of Nebraska Medical Center, Omaha 68198-6260, USA. dtmonagh@unmc.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9023271

Citation

Monaghan, D T., and H Larsen. "NR1 and NR2 Subunit Contributions to N-methyl-D-aspartate Receptor Channel Blocker Pharmacology." The Journal of Pharmacology and Experimental Therapeutics, vol. 280, no. 2, 1997, pp. 614-20.
Monaghan DT, Larsen H. NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology. J Pharmacol Exp Ther. 1997;280(2):614-20.
Monaghan, D. T., & Larsen, H. (1997). NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology. The Journal of Pharmacology and Experimental Therapeutics, 280(2), 614-20.
Monaghan DT, Larsen H. NR1 and NR2 Subunit Contributions to N-methyl-D-aspartate Receptor Channel Blocker Pharmacology. J Pharmacol Exp Ther. 1997;280(2):614-20. PubMed PMID: 9023271.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology. AU - Monaghan,D T, AU - Larsen,H, PY - 1997/2/1/pubmed PY - 1997/2/1/medline PY - 1997/2/1/entrez SP - 614 EP - 20 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 280 IS - 2 N2 - The potencies of various N-methyl-D-aspartate(NMDA) receptor channel blockers were determined at recombinant NMDA receptors containing differing combinations of NR1 and NR2 subunits expressed in Xenopus laevis oocytes. When the NR1 subunit was varied (NR1e/NR2A or NR1b/NR2A), none of the 9 channel blockers tested displayed a statistically different affinity. In contrast, altering NR2 composition changed the affinities of several channel blockers. Three of 10 compounds displayed significantly higher affinities for NR1b/NR2C receptors than NR1b/NR2A receptors, and three of five compounds had higher affinity at NR1b/NR2C than NR1b/NR2B receptors. Both MK-801 and N-[1-(2-thienyl)cyclohyxyl]piperidine displayed identical affinities at all receptor subunit combinations tested. However, these two compounds displayed significantly slower rates of blockade and unblockade at NR1b/NR2C than at NR1b/NR2A receptors, perhaps reflecting the shorter mean open times of NR1/NR2C receptors. NR1b/NR2B and NR1b/NR2A were distinguished by one of five compounds tested. Taken together, these results indicate that NR2 subunits impart differing pharmacological profiles to NMDA receptors; thus, it may be possible to develop NMDA receptor channel blocker antagonists of greater subtype selectivity. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9023271/NR1_and_NR2_subunit_contributions_to_N_methyl_D_aspartate_receptor_channel_blocker_pharmacology_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9023271 DB - PRIME DP - Unbound Medicine ER -