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

  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},

Effects of manipulation of N-methyl-D-aspartate receptors on imipenem/cilastatin-induced seizures in rats.

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.

Anticonvulsant effects of the glycine/NMDA receptor ligands d‐cycloserine and d‐serine but not R‐(+)‐HA‐966 in amygdala‐kindled rats

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.

Comparative analysis of seizures induced by intracerebroventricular administration of NMDA, kainate and quisqualate in mice

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.

High doses of memantine (1-amino-3,5-dimethyladamantane) induce seizures in kindled but not in non-kindled rats

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.

Contrasting Neurochemical Interactions of Tiletamine, a Potent Phencyclidine (PCP) Receptor Ligand, with the N‐Methyl‐D‐Aspartate‐Coupled and ‐Uncoupled PCP Recognition Sites

The paradoxical effects of tiletamines suggest that tiletamine might activate receptor(s) or neuronal pathways of unknown pharmacology.

Low Doses of the Glycine/NMDA Receptor Antagonist R‐(+)‐HA‐966 but not d‐Cycloserine Induce Paroxysmal Activity in Limbic Brain Regions of Kindled Rats

The changes in electrographic recordings seen after administration of (+)‐HA‐966 in kindled rats were almost absent in non‐kindled rats, indicating that kindling had increased the sensitivity to the paroxysmal effects of the glycine/NMDA receptor ligand.



Antagonism of N-methyl-D-aspartate (NMDA) evoked increases in cerebellar cGMP and striatal ACh release by phencyclidine (PCP) receptor agonists: evidence for possible allosteric coupling of NMDA and PCP receptors.

It is reported that phencyclidine receptor agonists demonstrated a noncompetitive antagonism of NMDA receptor agonist actions.

Hypoglycemia-induced neuronal damage prevented by an N-methyl-D-aspartate antagonist.

The results suggest that hypoglycemic neuronal damage is induced by NMDA receptor agonists, such as the excitatory amino acids or related compounds.

Anticonvulsant action of excitatory amino acid antagonists.

Specific antagonists of excitation that is caused by amino acids provide a new class of anticonvulsant agents, and the most potent such compound was 2-amino-7-phosphonoheptanoic acid.

The behavioral effects of phencyclidines may be due to their blockade of potassium channels.

It is suggested that the behavioral effects of PCP and m-amino-PCP, may be due to a block of K+ conductance and enhancement of transmitter release at central neurons.

The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate

The results suggest that reduction of synaptic excitation mediated via NMA receptors contributes to the anaesthetic/analgesic properties of these two dissociative anaesthetics.