Nitromemantine (developmental code name YQW-36) is a derivative of

memantine Memantine is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizziness. Severe side effects may include blood clots ...

developed in 2006 for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

. It has been shown to reduce

excitotoxicity In excitotoxicity, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamate become pathologically high, resulting in excessive stimulation of receptors. For example, when glutamate re ...

mediated by over-activation of the glutamatergic system, by blocking

NMDA receptors The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...

Pharmacology

Like memantine, nitromemantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors, however nitromemantine selectively inhibits extrasynaptic NMDA receptors while sparing normal physiological synaptic NMDA receptor activity, resulting in less side effects and a greater neuroprotective action, as well as stimulating regrowth of synapses with prolonged administration. The discoverers of nitromemantine have demonstrated that the amyloid-β peptide associated with Alzheimer's disease acts as an agonist at α7 nicotinic acetylcholine receptors, chronic overstimulation of which then results in uncontrolled release of

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can syn ...

, and consequent excitotoxicity. By blocking extrasynaptic NMDA receptors, nitromemantine is able to largely prevent this excitotoxicity while minimising the side effects usually seen with less selective NMDA antagonists. The

nitrate Nitrate is a polyatomic ion A polyatomic ion, also known as a molecular ion, is a covalent bonded set of two or more atoms, or of a metal complex, that can be considered to behave as a single unit and that has a net charge that is not zer ...

group of nitromemantine was found to bind to a second site on the extrasynaptic NMDA receptor which had previously been targeted with

nitroglycerin Nitroglycerin (NG), (alternative spelling of nitroglycerine) also known as trinitroglycerin (TNG), nitro, glyceryl trinitrate (GTN), or 1,2,3-trinitroxypropane, is a dense, colorless, oily, explosive liquid most commonly produced by nitrating g ...

, and this double action is thought to be responsible for the increased effectiveness of nitromemantine.

References

Adamantanes Amines Antidementia agents NMDA receptor antagonists Nitrate esters {{nervous-system-drug-stub

Pharmacology

See also

References