Non-competitive antagonists of excitatory amino acid receptors

  title={Non-competitive antagonists of excitatory amino acid receptors},
  author={J. Kemp and A. Foster and E. Wong},
  journal={Trends in Neurosciences},
Abstract Non-competitive antagonists have become important tools for investigating the basic mechanisms of NMDA receptor function. Such compounds (e.g. MK-801, PCP) are thought to act at the level of the NMDA receptor-associated ion channel and many show a marked use-dependence in their antagonist properties. Little information is available concerning selective non-competitive antagonists of quisqualate or kainate receptors. A number of structurally diverse compounds act as non-competitive… Expand
In vivo characterization of phencyclidine/σ agonist-mediated inhibition of nociception
Substance P and excitatory amino acids have been implicated as potential nociceptive neurotransmitters in several investigations. Excitatory amino acids acting at N-methyl-D-aspartate (NMDA)Expand
NMDA Receptor Antagonists and Their Potential as Neuroprotective Agents
L-Glutamate is the major excitatory transmitter in the mammalian central nervous system (CNS) and it mediates its effects by actions on a variety of ionotropic receptors and metabotropic receptors. Expand
Low affinity channel blocking (uncompetitive) NMDA receptor antagonists as therapeutic agents – toward an understanding of their favorable tolerability
Current research attempting to explain the improved tolerability of low affinity NMDA receptor antagonists is reviewed, finding kinetic properties, particularly rapid blocking rate, seem to be of key importance. Expand
Excitatory amino acid receptors: Multiplicity and ligand specificity of the NMDA and AMPA receptor subtypes
Abstract Central excitatory amino acid (EAA) receptors are most conveniently subdivided into five main classes, most of which, if not all, are heterogeneous: NMDA, AMPA, kainic acid (KAIN),Expand
Mechanisms of blockade of excitatory amino acid receptor channels.
The characteristics of the voltage-dependent block of activated channels by the dissociative anesthetic 'slow channel blockers' has unusual characteristics and hypotheses that have been put forward to explain the mechanisms involved are analyzed. Expand
Different modulation of the binding to two phencyclidine (PCP) receptor subtypes: Effects of N-methyl-d-aspartate agonists and antagonists
  • Y. Itzhak
  • Chemistry, Medicine
  • Neuroscience Letters
  • 1989
The present results indicate that the high (sigma p) and low-affinity (PCP) sites, that are distinct from the sigma h site, are affected differently by NMDA agonists and antagonists, and thus may represent different receptor domains. Expand
Differential effects of competitive and noncompetitive NMDA receptor antagonists on GABA turnover in the mouse brain
The modulation of GABA-mediated neurotransmission by excitatory amino acid inputs was examined by testing the effects of competitive NMDA receptor antagonists (CPP, CGS 19755, CGP 37849 and CGPExpand
The in vivo relevance of the varied channel-blocking properties of uncompetitive NMDA antagonists: tests on spinal neurones
Compared the effects of NMDA antagonists that display varied profiles of voltage-dependent block in vitro, on responses of spinal neurones in anaesthetised rats, memantine preferentially reduced "wind-up" relative to responses to pinch, whereas ketamine and MK-801 reduced both types of synaptic responses in parallel. Expand
The NMDA-receptor antagonist, MK-801, suppresses limbic kindling and kindled seizures
It was concluded that excitatory amino acid transmission contributes in an important, but non-critical way to amygdala kindling. Expand
Effects of the non-competitive NMDA-receptor antagonist memantine on morphine- and cocaine-induced potentiation of lateral hypothalamic brain stimulation reward
Abstract Rationale: NMDA-receptor antagonists may be of potential therapeutic use in several states of disease. It has been reported that drugs like MK-801 can potentiate the rewarding effects ofExpand


Ketamine acts as a non-competitive N-methyl-d-aspartate antagonist on frog spinal cord in vitro
Experiments in which combinations of drugs were tested indicated that these substances act by three distinct mechanisms to cause antagonism of the actions of NMDA. Expand
Voltage-dependent block by Mg2+ of NMDA responses in spinal cord neurones
Using voltage-clamp experiments on mouse spinal cord neurones, it is shown that the voltage-sensitivity of NMDA action is greatly reduced on the withdrawal of physiological concentrations (∼1 mM) of Mg2+ from the extracellular fluid, providing further evidence that Mg 2+ blocks inward current flow through ion channels linked to NMDA receptors. Expand
Glycine potentiates the NMDA response in cultured mouse brain neurons
G glycine may facilitate excitatory transmission in the brain through an allosteric activation of the NMDA receptor, and can be observed in outside-out patches as an increase in the frequency of opening of the channels activated by NMDA agonists. Expand
NMDA-receptor activation increases cytoplasmic calcium concentration in cultured spinal cord neurones
It is directly demonstrated that excitatory amino acids acting at NMDA receptors on spinal cord neurones increase the intracellular Ca2+ activity, measured using the indicator dye arsenazo III, and that this is the result of Ca2- influx through NMDA receptor channels. Expand
Magnesium gates glutamate-activated channels in mouse central neurones
The voltage dependence of the NMDA receptor-linked conductance appears to be a consequence of the voltage dependenceof the Mg2+ block and its interpretation does not require the implication of an intramembrane voltage-dependent ‘gate’. Expand
High correlation between the localization of [3H]TCP binding and NMDA receptors.
The regional binding distribution of the o-specific compound [3H]TCP and NMDA-sensitive [3h]glutamate binding sites within the rat CNS is compared using quantitative autoradiography to delineate the relationship between the dissociative anesthetics andNMDA receptors. Expand
Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons
In the mammalian central nervous system amino acids such as L-glutamate and L-aspartate are thought to act as fast synaptic transmitters1,2. It has been suggested that at least threeExpand
Glutamate activates multiple single channel conductances in hippocampal neurons
Four or more distinct single-channel currents are evoked by applying glutamate to each outside-out membrane patch, which are compatible with the model that all the single channel conductances activated by glutamate reflect the operation of one or two complex molecular entities. Expand
CNS depressants: Effects on post-synaptic pharmacology
  • J. Barker
  • Medicine, Chemistry
  • Brain Research
  • 1975
None of the agents tested altered hyperpolarizing, K+-dependent responses to dopamine and glutamate on the neurosecretory cell, nor did they affect either the induction or enhancement of BPP activity by the vertebrate peptide vasopressin on this cell. Expand
Ketamine and phencyclidine cause a voltage-dependent block of responses to l-aspartic acid
Under whole cell voltage-clamp (in the absence of extracellular Mg2+) this depression of responses to L-ASP was found to be highly voltage-dependent suggesting a blockade of the channel. Expand