NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology

Daniel T Monaghan, Heidi Larsen

Research output: Contribution to journalArticle

72 Citations (Scopus)

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 (NR1 e/NR2A or NR1 b/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.

Original languageEnglish (US)
Pages (from-to)614-620
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume280
Issue number2
StatePublished - May 3 1997

Fingerprint

N-Methyl-D-Aspartate Receptors
Pharmacology
Dizocilpine Maleate
Xenopus laevis
Oocytes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology. / Monaghan, Daniel T; Larsen, Heidi.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 280, No. 2, 03.05.1997, p. 614-620.

Research output: Contribution to journalArticle

@article{65788c61ef2442909061f34985acf92c,
title = "NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology",
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 (NR1 e/NR2A or NR1 b/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.",
author = "Monaghan, {Daniel T} and Heidi Larsen",
year = "1997",
month = "5",
day = "3",
language = "English (US)",
volume = "280",
pages = "614--620",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - NR1 and NR2 subunit contributions to N-methyl-D-aspartate receptor channel blocker pharmacology

AU - Monaghan, Daniel T

AU - Larsen, Heidi

PY - 1997/5/3

Y1 - 1997/5/3

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 (NR1 e/NR2A or NR1 b/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.

AB - 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 (NR1 e/NR2A or NR1 b/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.

UR - http://www.scopus.com/inward/record.url?scp=0030946384&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030946384&partnerID=8YFLogxK

M3 - Article

VL - 280

SP - 614

EP - 620

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -