BIOMAT Database Logo BIOMAT Database Logo

Pharmacological characterization of interactions of RO 25-6981 with the NR2B (epsilon2) subunit. 2001

D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Department of Neurology, University of Pennsylvania School of Medicine, Children's Seashore House, Philadelphia, PA 19104, USA. lynch@pharm.med.upenn.edu

We used ligand binding to ascertain whether the pharmacological actions of RO 25-6981 [(R:(*), S:(*))-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidinepropanol] match those of other NR2B (epsilon2) subunit specific agents. RO 25-6981 inhibited binding of 125I-MK801 [iodo-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohept-5,10-imine maleate] to receptors made from NR1a/epsilon2 but not NR1a/epsilon1. Increasing the concentration of spermidine did not change the efficacy of RO 25-6981 and minimally changed the IC(50) value. Chimeric epsilon1/epsilon2 receptors demonstrated that the structural determinants for high affinity actions of RO 25-6981 were contained completely within the first 464 amino acids, but no receptor retained wildtype features when the size of the epsilon2 component was decreased further. Epsilon1Q336R receptors were more inhibited by ifenprodil and RO 25-9681 than wildtype epsilon1 receptors in ligand binding assays but not in functional assays. Selected mutations of epsilon2E200 and epsilon2E201 also decreased the sensitivity of receptors to ifenprodil and RO 25-6981. These results suggest that RO 25-6981 shares structural determinants with ifenprodil and other modulators in the NR2B subunit.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D009154 Mutation Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations. Mutations
D010636 Phenols Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
D010880 Piperidines A family of hexahydropyridines.
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011993 Recombinant Fusion Proteins Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes. Fusion Proteins, Recombinant,Recombinant Chimeric Protein,Recombinant Fusion Protein,Recombinant Hybrid Protein,Chimeric Proteins, Recombinant,Hybrid Proteins, Recombinant,Recombinant Chimeric Proteins,Recombinant Hybrid Proteins,Chimeric Protein, Recombinant,Fusion Protein, Recombinant,Hybrid Protein, Recombinant,Protein, Recombinant Chimeric,Protein, Recombinant Fusion,Protein, Recombinant Hybrid,Proteins, Recombinant Chimeric,Proteins, Recombinant Fusion,Proteins, Recombinant Hybrid
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D006220 Haloperidol A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279) Haldol
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man

Related Publications

D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Ro 25-6981, a highly potent and selective blocker of N-methyl-D-aspartate receptors containing the NR2B subunit. Characterization in vitro.
December 1997, The Journal of pharmacology and experimental therapeutics,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Fear memory impairing effects of systemic treatment with the NMDA NR2B subunit antagonist, Ro 25-6981, in mice: attenuation with ageing.
January 2009, Pharmacology, biochemistry, and behavior,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Antiparkinsonian activity of Ro 25-6981, a NR2B subunit specific NMDA receptor antagonist, in animal models of Parkinson's disease.
May 2004, Experimental neurology,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Identification of critical residues in the amino terminal domain of the human NR2B subunit involved in the RO 25-6981 binding pocket.
December 2003, The Journal of pharmacology and experimental therapeutics,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
The NMDA receptor NR2B subtype selective antagonist Ro 25-6981 aggravates paroxysmal dyskinesia in the dt(sz) mutant.
January 2003, European journal of pharmacology,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Biopharmaceutical Characterization and Oral Efficacy of a New Rapid Acting Antidepressant Ro 25-6981.
September 2018, Journal of pharmaceutical sciences,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Different action of a specific NR2B/NMDA antagonist Ro 25-6981 on cortical evoked potentials and epileptic afterdischarges in immature rats.
February 2015, Brain research bulletin,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
In vitro binding properties in rat brain of [3H]Ro 25-6981, a potent and selective antagonist of NMDA receptors containing NR2B subunits.
May 1998, Journal of neurochemistry,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Neurogenesis enhancer RO 25-6981 facilitates repeated spatial learning in adult rats.
September 2012, Bulletin of experimental biology and medicine,
D R Lynch, and S S Shim, and K M Seifert, and S Kurapathi, and V Mutel, and M J Gallagher, and R P Guttmann
Fast NMDA receptor-mediated synaptic currents in neurons from mice lacking the epsilon2 (NR2B) subunit.
January 2000, Journal of neurophysiology,
Copied contents to your clipboard!