Tags

Type your tag names separated by a space and hit enter

Characterization of haloperidol and trifluperidol as subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonists using [3H]TCP and [3H]ifenprodil binding in rat brain membranes.
J Pharmacol Exp Ther. 1997 Feb; 280(2):584-92.JP

Abstract

[3H]TCP and [3H]ifenprodil binding to N-methyl-D-aspartate (NMDA) receptors in rat forebrain membranes was used to compare the inhibition of haloperidol and trifluperidol with that of ifenprodil and eliprodil. In the [3H]TCP binding assay, inhibition curves of ifenprodil, eliprodil, haloperidol and trifluperidol revealed two affinity states in the presence of glutamate, glycine and spermidine. The potency of these agents to inhibit the high-affinity fraction of the binding agreed with the results of other studies investigating their potency to block glutamate-induced current at recombinant NR1a/NR2B NMDA receptors expressed in Xenopus oocytes. These agents also inhibited [3H]ifenprodil binding in a biphasic manner, whether in the absence or the presence of either the sigma site ligand GBR-12909 or spermidine. Spermidine reduced the fraction of high-affinity sites labeled with [3H]ifenprodil. The only alteration in the affinity was a decrease in the IC50 value of haloperidol to inhibit the high-affinity fraction of [3H]ifenprodil binding. GBR-12909 also reduced the fraction of [3H]ifenprodil sites inhibited by these compounds with high affinity, with no change in the affinity for either fraction. These data suggest that spermidine is neither a competitive antagonist at the fraction of the binding inhibited by these agents with high affinity, nor is this fraction of the binding to sigma sites. Haloperidol and trifluperidol represent a new class of agent that interacts at a site that is labeled by [3H]ifenprodil as well as [3H]TCP in rat brain membranes and that closely reflects ifenprodil's voltage-independent site on the recombinant NR1a/NR2B subtype of the NMDA receptor.

Authors+Show Affiliations

Department of Neurological and Neurodegenerative Disease, Parke-Davis Pharmaceutical Research, Ann Arbor, Michigan 48105, USA.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9023267

Citation

Coughenour, L L., and J J. Cordon. "Characterization of Haloperidol and Trifluperidol as Subtype-selective N-methyl-D-aspartate (NMDA) Receptor Antagonists Using [3H]TCP and [3H]ifenprodil Binding in Rat Brain Membranes." The Journal of Pharmacology and Experimental Therapeutics, vol. 280, no. 2, 1997, pp. 584-92.
Coughenour LL, Cordon JJ. Characterization of haloperidol and trifluperidol as subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonists using [3H]TCP and [3H]ifenprodil binding in rat brain membranes. J Pharmacol Exp Ther. 1997;280(2):584-92.
Coughenour, L. L., & Cordon, J. J. (1997). Characterization of haloperidol and trifluperidol as subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonists using [3H]TCP and [3H]ifenprodil binding in rat brain membranes. The Journal of Pharmacology and Experimental Therapeutics, 280(2), 584-92.
Coughenour LL, Cordon JJ. Characterization of Haloperidol and Trifluperidol as Subtype-selective N-methyl-D-aspartate (NMDA) Receptor Antagonists Using [3H]TCP and [3H]ifenprodil Binding in Rat Brain Membranes. J Pharmacol Exp Ther. 1997;280(2):584-92. PubMed PMID: 9023267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Characterization of haloperidol and trifluperidol as subtype-selective N-methyl-D-aspartate (NMDA) receptor antagonists using [3H]TCP and [3H]ifenprodil binding in rat brain membranes. AU - Coughenour,L L, AU - Cordon,J J, PY - 1997/2/1/pubmed PY - 1997/2/1/medline PY - 1997/2/1/entrez SP - 584 EP - 92 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 280 IS - 2 N2 - [3H]TCP and [3H]ifenprodil binding to N-methyl-D-aspartate (NMDA) receptors in rat forebrain membranes was used to compare the inhibition of haloperidol and trifluperidol with that of ifenprodil and eliprodil. In the [3H]TCP binding assay, inhibition curves of ifenprodil, eliprodil, haloperidol and trifluperidol revealed two affinity states in the presence of glutamate, glycine and spermidine. The potency of these agents to inhibit the high-affinity fraction of the binding agreed with the results of other studies investigating their potency to block glutamate-induced current at recombinant NR1a/NR2B NMDA receptors expressed in Xenopus oocytes. These agents also inhibited [3H]ifenprodil binding in a biphasic manner, whether in the absence or the presence of either the sigma site ligand GBR-12909 or spermidine. Spermidine reduced the fraction of high-affinity sites labeled with [3H]ifenprodil. The only alteration in the affinity was a decrease in the IC50 value of haloperidol to inhibit the high-affinity fraction of [3H]ifenprodil binding. GBR-12909 also reduced the fraction of [3H]ifenprodil sites inhibited by these compounds with high affinity, with no change in the affinity for either fraction. These data suggest that spermidine is neither a competitive antagonist at the fraction of the binding inhibited by these agents with high affinity, nor is this fraction of the binding to sigma sites. Haloperidol and trifluperidol represent a new class of agent that interacts at a site that is labeled by [3H]ifenprodil as well as [3H]TCP in rat brain membranes and that closely reflects ifenprodil's voltage-independent site on the recombinant NR1a/NR2B subtype of the NMDA receptor. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/9023267/Characterization_of_haloperidol_and_trifluperidol_as_subtype_selective_N_methyl_D_aspartate__NMDA__receptor_antagonists_using_[3H]TCP_and_[3H]ifenprodil_binding_in_rat_brain_membranes_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9023267 DB - PRIME DP - Unbound Medicine ER -