Paradoxical convulsant action of a novel non-competitiveN-methyl-d-aspartate (NMDA) antagonist, tiletamine

@article{Klockgether1988ParadoxicalCA,
  title={Paradoxical convulsant action of a novel non-competitiveN-methyl-d-aspartate (NMDA) antagonist, tiletamine},
  author={Thomas Klockgether and Lechosław Turski and Michael Schwarz and K-H. Sontag and John C. Lehmann},
  journal={Brain Research},
  year={1988},
  volume={461},
  pages={343-348}
}
Intracerebroventricular (i.c.v.) injection of tiletamine, 0.001 mumol, a presumed non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, protected mice from convulsions induced by NMDA and quinolinate, but not from those induced by excitatory amino acids interacting preferentially with non-NMDA receptors. At higher doses, however, tiletamine induced convulsions by itself. Tiletamine-induced convulsions were antagonized by the broad spectrum excitatory amino acid antagonist, gamma… Expand
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Non-competitive N-methyl-D-aspartate antagonists protect against sound-induced seizures in DBA/2 mice.
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There is a close correlation between their relative anticonvulsant potencies and their potencies for displacing [3H]MK-801, phencyclidine, dextrorphan, SKF-10047 and ketamine. Expand
Differential effects of antiepileptic drugs and β-carbolines on seizures induced by excitatory amino acids
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Systemic administration showed that the benzodiazepines clonazepam and midazolam blocked convulsions induced by kainate and had no effect on seizures triggered by N-methyl-D-aspartate and quisqualate, while Ethosuximide increased the susceptibility of mice to N- methyl-D, aspartate, and had little or no impact on other types of seizures. Expand
Effects of a non-competitive N-methyl-d-aspartate (NMDA) antagonist, tiletamine, in adult zebrafish.
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These findings demonstrate potent neurotropic effects of tiletamine in zebrafish, and their high sensitivity to this drug, and support the growing utility of fish-based aquatic screens for studying neuroactive properties of NMDA antagonists in-vivo. Expand
Anticonvulsant activity of antagonists and partial agonists for the NMDA receptor-associated glycine site in the kindling model of epilepsy
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The data demonstrate that pharmacological manipulation of the glycine modulatory site of the NMDA receptor is an effective means of increasing seizure threshold in amygdala-kindled rats. Expand
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The results suggested that excitatory neurotransmission contributed to the generation and/or propagation of Imi/Cil-induced seizures in rats, and that the effects of NMDA antagonists depended on a particular binding site within the NMDA receptor complex, and affinity to that site. Expand
Anticonvulsant effects of the glycine/NMDA receptor ligands d‐cycloserine and d‐serine but not R‐(+)‐HA‐966 in amygdala‐kindled rats
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Pharmacological intervention at the strychnine‐insensitive glycine receptor by high‐efficacy partial agonists with systemic bioavailability may be an effective means of increasing seizure threshold without concomitantly inducing PCP‐like adverse effects. Expand
Comparative analysis of seizures induced by intracerebroventricular administration of NMDA, kainate and quisqualate in mice
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This study confirms that NMDA, KA and QA induce convulsions through different underlying mechanisms and suggests that different anatomical pathways are involved in these models. Expand
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The reported discrepancies about the effects of NO synthase inhibitors in seizure models are resolved by studying such drugs at various doses in a novel model of cortical seizure threshold, which is determined at short time intervals by applying ramp-shaped electrical pulse-trains directly to the cerebral cortex. Expand
High doses of memantine (1-amino-3,5-dimethyladamantane) induce seizures in kindled but not in non-kindled rats
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It is demonstrated that kindled rats are more sensitive to central nervous system stimulating effects of memantine than non-kindled rats, which could relate to an impairment of inhibitory processes and/or alterations in synaptic transmission mediated by excitatory amino acids in the kindled brain. Expand
Contrasting Neurochemical Interactions of Tiletamine, a Potent Phencyclidine (PCP) Receptor Ligand, with the N‐Methyl‐D‐Aspartate‐Coupled and ‐Uncoupled PCP Recognition Sites
TLDR
The paradoxical effects of tiletamines suggest that tiletamine might activate receptor(s) or neuronal pathways of unknown pharmacology. Expand
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