Nitromemantine

Nitromemantine

Clinical data
Other names	NitroMemantine; NitroSynapsin; YQW-36; YQW36; EM-036; EM036;
ATC code	None
Identifiers
IUPAC name 3-amino-5,7-diethyladamantan-1-yl nitrate
CAS Number	765890-91-3  Y
PubChem CID	130449551
UNII	VB3DW89EP2
CompTox Dashboard (EPA)	DTXSID301045555
Chemical and physical data
Formula	C14H24N2O3
Molar mass	268.357 g·mol−1
3D model (JSmol)	Interactive image
SMILES N[C@@]12C[C@]3(O[N+]([O-])=O)C[C@@](C2)(CC)C[C@@](C1)(CC)C3

Nitromemantine (developmental code names YQW-36 and EM-036), also known as NitroSynapsin, is a derivative of memantine developed in 2006 for the treatment of Alzheimer's disease. It has been shown to reduce excitotoxicity mediated by over-activation of the glutamatergic system, by blocking NMDA receptors. ^{[1] [2] [3]} It was being developed for treatment of Alzheimer's disease and pervasive developmental disorders like autism, but development was discontinued in 2023. ^[4]

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, 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. ^[5] The nitrate group of nitromemantine was found to bind to a second site on the extrasynaptic NMDA receptor which had previously been targeted with nitroglycerin, and this double action is thought to be responsible for the increased effectiveness of nitromemantine. ^[6]

See also

• Memantine
• Neramexane
• Amantadine

References

1. Lipton SA (February 2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond". Nature Reviews. Drug Discovery. 5 (2): 160–70. Bibcode:2006NRvDD...5..160L. doi:10.1038/nrd1958. PMID   16424917. S2CID   21379258.
2. Nakamura T, Lipton SA (February 2010). "Preventing Ca2+-mediated nitrosative stress in neurodegenerative diseases: possible pharmacological strategies". Cell Calcium. 47 (2): 190–7. doi:10.1016/j.ceca.2009.12.009. PMC   2875138 . PMID   20060165.
3. Labra SR, Compher J, Prabhavalkar A, Almaraz M, Kwong CC, Baal C, Talantova M, Dolatabadi N, Piña-Sanz J, Wang Y, Yoon L, Ghatak S, Gao Z, Zhang Y, Trudler D, Massey L, Lin W, Balistreri A, Bula M, Schork NJ, Mondala TS, Head SR, Kelly JW, Lipton SA (July 2025). "Autophagy activators normalize aberrant Tau proteostasis and rescue synapses in human familial Alzheimer's disease iPSC-derived cortical organoids". bioRxiv   10.1101/2025.06.25.661453 . S.A.L discloses that he is an inventor on worldwide patents for the use of memantine and NitroSynapsin (aka NitroMemantine, YQW-036, or EM-036) for neurodegenerative and neurodevelopmental disorders.
4. "EM 036". AdisInsight. 20 February 2023. Retrieved 26 January 2026.
5. Talantova M, Sanz-Blasco S, Zhang X, Xia P, Akhtar MW, Okamoto S, et al. (July 2013). "Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss". Proceedings of the National Academy of Sciences of the United States of America. 110 (27): E2518-27. Bibcode:2013PNAS..110E2518T. doi: 10.1073/pnas.1306832110 . PMC   3704025 . PMID   23776240.
6. Lieberman B (June 17, 2013). "Reversing the loss of brain connections in Alzheimer's disease". Beaker. Sanford-Burnham Science Blog.