Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats

@article{Nicholson2003EvaluationOT,
  title={Evaluation of the phencyclidine-like discriminative stimulus effects of novel NMDA channel blockers in rats},
  author={Katherine L. Nicholson and Robert L. Balster},
  journal={Psychopharmacology},
  year={2003},
  volume={170},
  pages={215-224}
}
RationaleBecause of their potential therapeutic effects, N-methyl-d-aspartate (NMDA) receptor antagonists have been investigated for clinical use. Unfortunately, many channel-blocking antagonists have been associated with the production of side effects, including motor impairment and phencyclidine (PCP)-like subjective effects.ObjectiveThis study investigated the relationship between NMDA receptor channel blockade and production of PCP-like side effects by evaluating a variety of NMDA channel… 

The discriminative stimulus effects of N-methyl-d-aspartate glycine-site ligands in NMDA antagonist-trained rats

TLDR
Evidence is provided that NMDA glycine-site partial agonists and antagonists generally do not produce discriminative stimulus effects similar to those of representative NMDA channel blockers or competitive antagonists.

GLYX-13, an NMDA receptor glycine site functional partial agonist enhances cognition and produces antidepressant effects without the psychotomimetic side effects of NMDA receptor antagonists

TLDR
Understanding the mechanistic underpinning of GLYX-13's antidepressant action should provide both novel insights into the role of the glutamatergic system in depression and identify new targets for therapeutic development.

Application and Assessment of Deep Learning for the Generation of Potential NMDA Receptor Antagonists

TLDR
This study applies a variety of ligand- and structure-based assessment techniques used in standard drug discovery analyses to the deep learning-generated compounds, and presents twelve candidate antagonists that are not available in existing chemical databases to provide an example of what this type of workflow can achieve.

Synthesis and analgesic effects of new pyrrole derivatives of phencyclidine in mice.

TLDR
It is concluded that substitution of the aromatic pyrrole ring instead of piperidine in the PCP molecule will not be effective alone in tail immersion and formalin tests but the addition of a methyl group (with high electron donating and dipole moments) on the phenyl group can be effective in acute and chronic pain compared to thePCP and control groups.

Synthesis and analgesic effects of 1-[1-(2-methylphenyl)(cyclohexyl)]-3-piperidinol as a new derivative of phencyclidine in mice.

TLDR
It is concluded that II is effective in acute thermal (in all doses) and chronic (doses of 5 and 10 mg/kg) pains; however, it is noteffective in acute chemical pain compared to PCP and control.

NMDA Receptors Containing the GluN2D Subunit Control Neuronal Function in the Subthalamic Nucleus

TLDR
Results demonstrate that pharmacologic modulation of GluN2D-containing receptors alters the time course of EPSCs and controls the in vivo spike-firing rate in the STN, and may represent potential therapeutic targets for modulating subthalamic neuron activity in neurological disorders such as Parkinson's disease.

1-Methyl-1,2,3,4-Tetrahydroisoquinoline, an Endogenous Amine with Unexpected Mechanism of Action: New Vistas of Therapeutic Application

TLDR
The results strongly support the view that 1MeTIQ has a considerable potential as a drug for combating substance abuse, through the attenuation of craving, and believe that MAO inhibition, free radicals scavenging properties, and antagonism to the glutamatergic system may play an essential role in neuroprotection.

1-Methyl-1,2,3,4-Tetrahydroisoquinoline: A Potent Neuroprotecting Agent

TLDR
1-Methyl-1,2,3,4-tetrahydroisoquinoline offers a unique and complex mechanism of neuroprotection in which free radicals scavenging properties and inhibition of glutamate-induced excitotoxicity may play a very important role, and indicates the potential of 1MeTIQ as a therapeutic agent in various neurodegenerative illnesses of the central nervous system.

References

SHOWING 1-10 OF 80 REFERENCES

Behavioral effects and anticonvulsant efficacies of low-affinity, uncompetitive NMDA antagonists in mice

TLDR
Findings indicate that only certain low-affinity, uncompetitive NMDA antagonists (e.g., memantine) may have therapeutic efficacy at doses that do not produce an adverse side-effect profile.

Phencyclidine-like discriminative stimulus properties of MK-801 in rats.

Clinically available NMDA receptor antagonists memantine and dextromethorphan reverse existing tolerance to the antinociceptive effects of morphine in mice

TLDR
The data indicate that low-affinity, clinically available and/or therapeutically promising NMDA receptor antagonists may be used to inhibit ongoing morphine tolerance.

Effects of the NMDA receptor channel blockers memantine and MRZ 2/579 on morphine withdrawal-facilitated aggression in mice

TLDR
Taking together with the evidence on the lack of selective anti-aggressive effects of these drugs in morphine-naive mice, attenuation of the aggression observed in the present study may be due to specific interaction with morphine withdrawal-triggered processes.

The discriminative stimulus effects of N-methyl-d-aspartate antagonists in phencyclidine-trained rats

Evaluation of the reinforcing properties and phencyclidine-like discriminative stimulus effects of dextromethorphan and dextrorphan in rats and rhesus monkeys

TLDR
DXM has some PCP-like effects in rats and monkeys, but that they are more reliably produced by its metabolite, DXO, and this potential may be associated with, or enhanced by, metabolism of DXM to DXO.

Anticonvulsant efficacy of N-methyl-D-aspartate antagonists against convulsions induced by cocaine.

TLDR
The present results provide the most extensive evidence to date identifying NMDA receptor blockade as a potential strategy for the discovery of agents for clinical use in averting toxic sequelae from cocaine overdose.

Behavioral studies on FR115427, a novel selective N-methyl-D-aspartate antagonist

TLDR
The results suggest that FR115427 is a novel non-competitive NMDA antagonist that acts on a binding site located within the NMDA receptor associated ion channel.
...