NDLI: Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.

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Capelli bitableaux and Z-forms of general linear Lie superalgebras.

Do thylakoids really contain phosphatidylcholine?

Holomorphic curves in surfaces of general type.

Nonminimum phase non-Gaussian autoregressive processes.

Determination of the crystal structure and composition of Li6Be4OH12 by the stochastic method.

Bialgebra cohomology, deformations, and quantum groups.

Expression of functional pituitary somatostatin receptors in Xenopus oocytes.

Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies.

Long-distance activation of the Myc protooncogene by provirus insertion in Mlvi-1 or Mlvi-4 in rat T-cell lymphomas.

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Constitutive expression of growth-related mRNAs in proliferating and nonproliferating lung epithelial cells in primary culture: evidence for growth-dependent translational control.

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Mammalian dihydroorotase: nucleotide sequence, peptide sequences, and evolution of the dihydroorotase domain of the multifunctional protein CAD.

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Molecular dissection of mutations at the heterozygous thymidine kinase locus in mouse lymphoma cells.

Spectroscopic studies of wild-type and mutant 'zinc finger' peptides: determinants of domain folding and structure.

Active-site zinc ligands and activated H2O of zinc enzymes.

Albumin Redhill (-1 Arg, 320 Ala----Thr): a glycoprotein variant of human serum albumin whose precursor has an aberrant signal peptidase cleavage site.

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Characterization of a class of nonformylated Enterococcus faecalis-derived neutrophil chemotactic peptides: the sex pheromones.

Higher order nuclear organization: three-dimensional distribution of small nuclear ribonucleoprotein particles.

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Pasteurella multocida toxin: potent mitogen for cultured fibroblasts.

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Identification of a noncatalytic cGMP-binding domain conserved in both the cGMP-stimulated and photoreceptor cyclic nucleotide phosphodiesterases.

Bovine cone photoreceptor cGMP phosphodiesterase structure deduced from a cDNA clone.

Identification and characterization of a Neisseria gonorrhoeae gene encoding a glycolipid-binding adhesin.

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Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.

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Identification of a viral gene encoding a ubiquitin-like protein.

Labile disulfide bonds in human placental insulin receptor.

Selectivity of phospholipase C phosphorylation by the epidermal growth factor receptor, the insulin receptor, and their cytoplasmic domains.

Human papilloma virus DNAs immortalize normal human mammary epithelial cells and reduce their growth factor requirements.

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Identification of heat shock protein hsp70 homologues in chloroplasts.

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Gene imprinting and major histocompatibility complex class I antigen expression in the rat placenta.

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Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity.

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Bacteriophage P1 cloning system for the isolation, amplification, and recovery of DNA fragments as large as 100 kilobase pairs.

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Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Marshall, G. R. Singh, L. Oles, R. J. Foster, A. C. Hutson, P. H. Leeson, P. D. Donald, A. E. Iversen, L. L. Iversen, S. D. Kemp, J. A.
Description	Author Affiliation: Singh L ( Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, United Kingdom.);
Abstract	The antagonist effect of (+/-)-3-amino-1-hydroxypyrrolid-2-one (HA-966) at the N-methyl-D-aspartate (NMDA) receptor occurs through a selective interaction with the glycine modulatory site within the receptor complex. When the enantiomers of (+/-)-HA-966 were resolved, the (R)-(+)-enantiomer was found to be a selective glycine/NMDA receptor antagonist, a property that accounts for its anticonvulsant activity in vivo. In contrast, the (S)-(-)-enantiomer was only weakly active as an NMDA-receptor antagonist, but nevertheless it possessed a marked sedative and muscle relaxant action in vivo. In radioligand binding experiments, (+)-HA-966 inhibited strychnine-insensitive [3H]glycine binding to rat cerebral cortex synaptic membranes with an IC50 of 12.5 microM, whereas (-)-HA-966 had an IC50 value of 339 microM. In electrophysiological experiments, (+)-HA-966 selectively antagonized NMDA receptor responses in rat cortical slices, whereas the (-)-enantiomer was much weaker. On cultured cortical neurones (+)-HA-966 inhibited glycine-potentiated NMDA responses with an IC50 = 13 microM compared with (-)-HA-966, which has an IC50 = 708 microM. In agreement with findings with racemic HA-966, even high concentrations of (+)-HA-966 did not completely inhibit NMDA responses, suggesting that (+)-HA-966 is a low-efficacy partial agonist. (+)-HA-966 produced parallel shifts to the right of the glycine concentration curve for potentiation of NMDA responses, resulting in an estimated pKb = 5.6. In mice, (+)-HA-966 antagonized sound and N-methyl-DL-aspartic acid (NMDLA)-induced seizures with ED50 values of 52.6 mg/kg of body weight (i.p.) and 900 mg/kg (i.v.), respectively. The coadministration of D-serine dose-dependently (10-100 micrograms into the cerebral ventricles per mouse) antagonized the anticonvulsant effect of a submaximal dose of (+)-HA-966 (100 micrograms administered directly into the cerebral ventricles) against NMDLA-induced seizures. The sedative/ataxic effect of racemic HA-966 was mainly attributable to the (-)-enantiomer, which was greater than 25-fold more potent than the (+)-enantiomer. It is suggested that, as in the case of the sedative gamma-butyrolactone, disruption of striatal dopaminergic mechanisms may be responsible for this action.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	1
Volume Number	87
Language	English
Publisher	National Academy of Sciences
Publisher Date	1990-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	4-Butyrolactone Pharmacology Aspartic Acid Analogs & Derivatives Cerebral Cortex Physiology Furans Glycine Pyrrolidinones Receptors, Neurotransmitter Acoustic Stimulation Animals Drug Effects Metabolism Corpus Striatum Dopamine In Vitro Techniques Isomerism Kinetics Membrane Potentials Mice Mice, Inbred DBA Motor Activity N-Methylaspartate Rats, Inbred Strains Receptors, Glycine Receptors, N-Methyl-D-Aspartate Reference Values Seizures Physiopathology Serotonin Comparative Study Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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