Name:	Neramexane
Other Names:	1-amino-1,3,3,5,5-pentamethyl-cyclohexane hydrochloride , MRZ 2/579
Therapeutic Applications:	Neuroprotective agent, acute and chronic neurodegeneration
Therapy Types:	Pharmaceutical, small molecule
Mechanisms:	Uncompetitive NMDA receptor channel blocker
Development Status:	investigational in U.S.
FDA Phase:	Discontinued
Primary Medical Role:	Similar to memantine (Namenda), neramexane’s effect as a neuroprotective agent is through its action as a fast kinetic, uncompetitive, open-channel NMDA receptor antagonist that blocks excessive NMDA receptor activity without disrupting normal activity or synaptic plasticity, appears to protect neurons from the damaging effects resulting from abnormal glutamatergic activity.
Role in Alzheimer's Disease:	Neramexane is similar to memantine and acetylcholinesterase inhibitors in that neramexane targets the cognitive decline in Alzheimer’s Disease by altering neurotransmitter signaling, but not the underlying pathological mechanisms that cause the disease (amyloid production or neurofibrillary tangle accumulation).
Pharmacological Role:	Neramexane is a low to moderate-affinity, uncompetitive NMDA receptor antagonist, believed to selectively block the excitotoxic effects associated with abnormal transmission of glutamate.
Contraindications:	No safety issues identified in clinical studies.
Side Effects:	unknown.
Evidence pro its efficacy:	July 14, 2005 Forest Laboratories, Inc. announced that a recently completed placebo-controlled proof of concept study of neramexane in the treatment of moderate to severe Alzheimer's disease showed sufficient clinical activity, safety, and tolerability to continue development of the compound.
Evidence con its efficacy:	Memantine efficacy is short-lived, and does not affect disease progression. Unlikely any other compound with similar mechanism of action will demonstrate significant change.
Companies:	Forest Laboratories, Inc., Merck & Co., Inc.

References

Danysz W, Parsons CG. Neuroprotective potential of ionotropic glutamate receptor antagonists. Neurotox Res. 2002 Mar ;4(2):119-26. Abstract

Danysz W, Parsons CG, Jirgensons A, Kauss V, Tillner J. Amino-alkyl-cyclohexanes as a novel class of uncompetitive NMDA receptor antagonists. Curr Pharm Des. 2002;8(10):835- 43. Abstract

Rammes G, Rupprecht R, Ferrari U, Zieglgansberger W, Parsons CG. The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl- cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non- competitive manner. Neurosci Lett. 2001 Jun 22;306(1-2):81- 4. Abstract

Houghton AK, Parsons CG, Headley PM. Mrz 2/579, a fast kinetic NMDA channel blocker, reduces the development of morphine tolerance in awake rats. Pain. 2001 Apr;91(3):201- 7. Abstract

Parsons CG, Danysz W, Quack G. Memantine and the amino- alkyl-cyclohexane MRZ 2/579 are moderate affinity uncompetitive NMDA receptor antagonists--in vitro characterisation. Amino Acids. 2000;19(1):157-66. Abstract