Activation of Brain Histaminergic Neurotransmission: A Mechanism for Cognitive Effects of Memantine in Alzheimer's Disease

@article{Motawaj2011ActivationOB,
  title={Activation of Brain Histaminergic Neurotransmission: A Mechanism for Cognitive Effects of Memantine in Alzheimer's Disease},
  author={Mouhammad Motawaj and Aude Burban and Elisabeth Davenas and J-M. Arrang},
  journal={Journal of Pharmacology and Experimental Therapeutics},
  year={2011},
  volume={336},
  pages={479 - 487}
}
We previously reported that some N-methyl-d-aspartate (NMDA)-receptor antagonists enhanced histamine neuron activity in rodents. Here, we have investigated the effects of memantine, an NMDA-receptor antagonist used for the treatment of Alzheimer's disease, on histaminergic neurotransmission. In vitro, memantine antagonized native NMDA receptors with a micromolar potency but had no effect at recombinant human histamine receptors. In vivo, a single administration of memantine increased histamine… 
View on Publisher
jpet.aspetjournals.org
25 Citations
Highly Influential Citations
1
Background Citations
12
Methods Citations
1

Figures and Tables from this paper

25 Citations

Citation Type

Citation Type

Effects of memantine on hippocampal long-term potentiation, gamma activity, and sensorimotor gating in freely moving rats
Mechanism of the histamine H3 receptor-mediated increase in exploratory locomotor activity and anxiety-like behaviours in mice
Inhibition of Astrocytic Histamine N-Methyltransferase as a Possible Target for the Treatment of Alzheimer’s Disease
TLDR
Increasing histamine levels could be employed in AD patients as co-therapy due to their effects on cognitive functions, neuroplasticity, neuronal survival, neurogenesis, and the degradation of amyloid beta (Aβ) peptides.
The central histamine level in rat model of vascular dementia.
TLDR
The rat vascular dementia model supports deficiency in histaminergic system in VD because of drastically increased latency and run time following permanent bilateral occlusion of the common carotid arteries leading to chronic cerebral hypoperfusion.
Modulation of behavior by the histaminergic system: Lessons from HDC-, H3R- and H4R-deficient mice
Memantine: a treatment for Alzheimer's disease with a new formulation
TLDR
Memantine ER was evaluated in a 24-week placebo-controlled trial of patients with moderate-to-severe AD, which found significant benefits for cognition, global assessment, behavior and caregiver burden, but not function.
Histaminergic Modulation of Recognition Memory
Altered nociception in mice with genetically induced hypoglutamatergic tone
Galantamine-memantine combination superior to donepezil-memantine combination in Alzheimer’s disease: critical dissection with an emphasis on kynurenic acid and mismatch negativity
TLDR
Galantamine and memantine via the α7nACh and NMDA receptors can counteract the effects of kynurenic acid and enhance MMN and BDNF and future studies with the galantamine-memantine combination with KP metabolites, MMN, andBDNF as biomarkers are warranted.
Cell proliferation in the hippocampus and in the heart is modified by exposure to repeated stress and treatment with memantine.
...
1
2
3
...

References

SHOWING 1-10 OF 46 REFERENCES
Memantine Blocks α7* Nicotinic Acetylcholine Receptors More Potently Than N-Methyl-D-aspartate Receptors in Rat Hippocampal Neurons
TLDR
It is suggested that blockade of α7* nAChRs by memantine could decrease its effectiveness for treatment of AD, particularly at early stages when the degrees of nA cholinergic dysfunction and of cognitive decline correlate well.
Memantine displaces [3H]MK-801 at therapeutic concentrations in postmortem human frontal cortex.
Memantine: a NMDA receptor antagonist that improves memory by restoration of homeostasis in the glutamatergic system - too little activation is bad, too much is even worse
Histamine Potentiates N-Methyl-d-aspartate Receptors by Interacting with an Allosteric Site Distinct from the Polyamine Binding Site
TLDR
The histamine-induced potentiation of NMDARs occurs in the brain under normal conditions, and histamine does not bind to the polyamine site, but to a distinct entity, the so-called histamine site of the N MDAR.
Mechanism of action of memantine.
Changes in cerebral neurotransmitters and metabolites induced by acute donepezil and memantine administrations: A microdialysis study
The Neuroprotective Agent Memantine Induces Brain-Derived Neurotrophic Factor and trkB Receptor Expression in Rat Brain
TLDR
Data suggest that the neuroprotective properties of memantine could be mediated by the increased endogenous production of BDNF in the brain, which may open up new possibilities of pharmacologically regulating the expression of neurotrophic factors in thebrain.
Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist—a review of preclinical data
CSF levels of the histamine metabolite tele-methylhistamine are only slightly decreased in Alzheimer's disease.
TLDR
Despite the strong degeneration of histamine neurons in the disease, t-MeHA levels in CSF were only slightly decreased in AD compared to controls, and the limited magnitude of the decrease in AD even at late stages may result from the compensatory activation of spared neurons, as well as the neuroinflammation-induced activation of microglia occurring in senescence and AD.
Changes in Histamine H3 Receptor Responsiveness in Mouse Brain
TLDR
Hypersensitivity at H3 somatodendritic autoreceptors and at heteroreceptor attributable to an increased number of HA binding sites could account for the various changes observed in this study.
...
1
2
3
4
5
...