The N-methyl-d-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT3 receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner

@article{Rammes2001TheNR,
  title={The N-methyl-d-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT3 receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner},
  author={Gerhard Rammes and Rainer Rupprecht and U Ferrari and Walter Zieglg{\"a}nsberger and Chris G. Parsons},
  journal={Neuroscience Letters},
  year={2001},
  volume={306},
  pages={81-84}
}
The type 3 serotonin (5-HT(3)) receptor is a ligand-gated ion channel. In concentration-clamp experiments, we investigated the effects of the uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists memantine, amantadine and MRZ 2/579 on 5-HT receptors stabley expressed in HEK-293 cells and on native 5-HT(3) receptors in the N1E-115 cell line. All agents antagonized serotonin (10 microM)-induced inward currents with similar potency to that reported for NMDA receptors. This effect was… Expand
Inhibition of the α9α10 nicotinic cholinergic receptor by neramexane, an open channel blocker of N-methyl-d-aspartate receptors
In this study we report the effects of neramexane, a novel amino-alkyl-cyclohexane derivative that is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, on recombinant rat alpha 9Expand
Antipsychotic drugs antagonize human serotonin type 3 receptor currents in a noncompetitive manner
TLDR
Since 5-HT3 receptors modulate mesolimbic and mesocortical dopaminergic activity, the functional antagonism of neuroleptics at 5- HT3 receptors may contribute to their antipsychotic efficacy and may constitute a not yet recognized pharmacological principle of these drugs. Expand
Effects of low-affinity NMDA receptor channel blockers in two rat models of chronic pain
TLDR
Low efficacy of acute administration ofNMDA receptor antagonists in the models of established pain states is confirmed and studies on the prevention and management of chronic pain should focus on preemptive or long-term administration of NMda receptor antagonists. Expand
Antidepressants are functional antagonists at the serotonin type 3 (5-HT3) receptor
Antidepressants are commonly supposed to enhance serotonergic and/or noradrenergic neurotransmission by inhibition of neurotransmitter reuptake through binding to the respective neurotransmitterExpand
Functional in vitro characterization of CR 3394: A novel voltage dependent N-methyl-d-aspartate (NMDA) receptor antagonist
TLDR
The data highlight pharmacological features of CR 3394 in vitro that prompt it as a candidate for the treatment of neurodegenerative disorders and strongly reduced glutamate- and NMDA-induced neuronal death in an in vitro model of neurotoxicity. Expand
Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test
TLDR
The results of this study suggest that the positive effects of 5-HT3 antagonists on the coping behavior of mice in FST and TST are at least partly mediated through NMDA receptors participation. Expand
Inhibition of human α7 nicotinic acetylcholine receptors by open channel blockers of N‐methyl‐D‐aspartate receptors
Human α7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N‐methyl‐D‐aspartate (NMDA) receptor open channel blockers memantine and cerestat on thisExpand
Role of N-Methyl-D-aspartate Receptors in Antidepressant-Like Effects of σ1 Receptor Agonist 1-(3,4-Dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine Dihydrochloride (SA-4503) in Olfactory Bulbectomized Rats
TLDR
The present study indicated for the first time that the σ1 receptor agonist SA-4503 may have effects on depressive symptoms such as agitation, loss of interest, and impaired cognition, which are mediated by NMDA receptors. Expand
Neramexane: a moderate-affinity NMDA receptor channel blocker: new prospects and indications
  • G. Rammes
  • Medicine
  • Expert review of clinical pharmacology
  • 2009
TLDR
Moderate-affinity, voltage-dependent, open-channel blockers, such as memantine and neramexane are useful therapeutics as they prevent the pathological activation of NMDA receptors but allow their physiological activity and should prove to be useful therapeuers in a wide range of CNS disorders. Expand
Memantine Inhibits ATP-Dependent K+ Conductances in Dopamine Neurons of the Rat Substantia Nigra Pars Compacta
TLDR
Results highlight KATP channels as possible relevant targets of Memantine effects in the brain and suggest another mechanism of action underlying the protective role of memantine in Parkinson's disease. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 19 REFERENCES
Amino-alkyl-cyclohexanes are novel uncompetitive NMDA receptor antagonists with strong voltage-dependency and fast blocking kinetics: in vitro and in vivo characterization
TLDR
The present study characterized the in vitro NMDA receptor antagonistic properties of novel amino-alkyl-cyclohexane derivatives and compared these effects with their ability to block excitotoxicity in vitro and MES-induced convulsions in vivo, indicating similar access of most compounds to the CNS. Expand
Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo
TLDR
The data from the present study do not lend support to the idea that low affinity, open channel NMDA receptor blockers are also effective in models of epilepsy at doses having little effect on physiological processes and do not contradict the known therapeutic safety of memantine and amantadine in dementia and Parkinson's disease respectively. Expand
5-HT3 Receptors in Outside-out Patches of N1E-115 Neuroblastoma Cells: Basic Properties and Effects of Pentobarbital
TLDR
The results obtained in this model are compatible with the suggestion that the inhibitory action of pentobarbital on 5-HT3 receptors is dependent on the agonist-activated (open) channel. Expand
Effects of antidepressants on the inward current mediated by 5‐HT3 receptors in rat nodose ganglion neurones
  • P. Fan
  • Chemistry, Medicine
  • British journal of pharmacology
  • 1994
TLDR
The results suggest that the 5‐HT3 receptor is an acting site for the therapeutic use of antidepressants and is also helpful in explaining the analgesic effect of antidepressants seen in pain clinics. Expand
Physiological and pharmacological properties of 5-HT3 receptors — A patch clamp-study
TLDR
The results of ion substitution experiments suggest that the 5-HT activated ion channel is permeable to both Na+ and K+ ions with a permeability ratio (PNa/PK) of 0.94 and 0.92 for rabbit nodose ganglion cells and N1E-115 cells respectively. Expand
5-HT3 receptors and the neural actions of alcohols: an increasingly exciting topic
  • D. Lovinger
  • Chemistry, Medicine
  • Neurochemistry International
  • 1999
TLDR
The current understanding of the role of the 5-HT3 receptor in alcohol abuse and alcoholism will be reviewed and an overview of the mechanism of alcohol actions of the receptor is provided. Expand
The psychopharmacology of 5-HT3 receptors.
TLDR
The use of 5-HT3 receptor antagonists reveals an important role for 5-hydroxytryptamine in the control of disturbed behavior in the absence of effect on normal behavior. Expand
Limbic mechanisms of anxiolytics acting on 5-HT receptors.
TLDR
It is concluded that both postsynaptic inhibition of the temporal lobe function (the hippocampus), and attenuation of the cell body firing of the raphe neurons appears to be important elements of anti-anxiety action of benzodiazepines and 5-HT1A receptor antagonists. Expand
Review of the results from clinical studies on the efficacy, safety and tolerability of mirtazapine for the treatment of patients with major depression.
TLDR
Mirtazapine is a unique addition to the antidepressant armamentarium as first-line therapy in patients with major depression and symptoms of anxiety/agitation or anxiety/somatization or complaints of insomnia and as a useful alternative in depressed patients who do not adequately respond to or are intolerant of tricyclic antidepressants or serotonin-specific reuptake inhibitors. Expand
Pharmacology of antidepressants: selectivity or multiplicity?
  • H. Westenberg
  • Medicine, Psychology
  • The Journal of clinical psychiatry
  • 1999
TLDR
The latest development has been the introduction of the noradrenergic and specific serotonergic antidepressant mirtazapine, which appears to be related to dual enhancement of central noraderepinephrine and Serotonergic neurotransmission by blockade of alpha2-adrenoceptors. Expand
...
1
2
...