The N-methyl-D-aspartate receptor ( NMDA receptor) is a glutamate receptor and ion channel protein found in nerve cells.
NMDARs require the binding of two molecules of glutamate or aspartate and two of glycine.
It is one of three types of ionotropic glutamate receptors.
The other receptors are the AMPA and kainate receptors.
It is activated when glutamate and glycine bind to it.
When NMDA is activated it allows positively charged ions to flow through the cell membrane.
It is very important for controlling synaptic plasticity and memory function.
The NMDAR is a specific type of glutamate receptor.
Activation of NMDA receptors results in the opening of an ion channel that is nonselective to cations.
Ca2+ flux through NMDARs is likely to be critical in for cellular mechanisms for learning and memory.
It is primarily a ligand-gated channel, but does have weaker voltage-dependence modulation of the ligand-dependent gating.
It requires co-activation by two ligands: glutamate and either D-serine or glycine.
NMDA is an excitatory receptor in the brain, when activated normally the receptor acts as an ion channel and there is an influx of positive ions through the channel to cause nerve cell depolarisation.
The NMDA receptor is affected by many psychoactive drugs such as phencyclidine (PCP), alcohol (ethanol) and dextromethorphan (DXM).
The anaesthetic and analgesic effects of ketamine and nitrous oxide are partially because of effects on NMDA receptor activity.
Memantine has been recognized to be an uncompetitive antagonist of the N-methyl-D-aspartate receptor, entering the channel of the receptor after it has been activated and thereby blocking the flow of ions.
The NMDA receptor channels play an important role in synaptic plasticity and synapse formation.
The NMDA receptor channels underly memory, learning and formation of neural networks during development in the central nervous system.
Overactivation of the receptor, causes excessive influx of Ca2+ and leads to excitotoxicity.
Decreased function of NMDA receptors
may be involved in impairment of synaptic plasticity and could have other negative repercussions.
The physiological actions of the NMDA receptor are essential for normal neuronal function.
NMDA receptors were associated with a variety of neurological disorders such as epilepsy, Parkinson’s, Alzheimer’s, Huntington’s and other CNS disorders.
-methyl-D-aspartate (NMDA) receptor activation following brain injuries can lead to calcium entry which triggers neuronal death via the mechanisms of excitotoxicity.
Memantine has been recognized to be an uncompetitive antagonist of the NMDA receptor.
The NR2B subunit has been involved in activities such as learning, memory, processing and feeding behaviors, as well as being implicated in number of human derangements.
Overactivation of NMDA receptors, relieving the Mg2+ block and causing excessive influx of Ca2+ can lead to excitotoxicity.
Excitotoxicity may be involved in some neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease.
Uncompetitive NMDA receptor antagonists enter the channel of the NMDA receptor after it has been activated and thereby block the flow of ions: ketamine, amantadine and memantine are examples of such antagonists
Memantine is an uncompetitive channel blocker of the NMDA receptor, and mimics the physiological function of Mg2+ as channel blocker.
Memantine only blocks NMDA during prolonged activation of the receptor, as it occurs under excitotoxic conditions, by replacing magnesium at the binding site.
NMDA receptors are also associated with synaptic plasticity.
Excitotoxicity has been thought to play a role in the degenerative properties of neurodegenerative conditions.
NMDA receptors play an important role in many of these degenerative diseases affecting the brain: Alzheimer’s disease and Huntington’s disease, and other medical conditions such as strokes and epilepsy.
Glutamic acid (glutamate), is the major endogenous agonist of the NMDAR.
Glycine is the major endogenous agonist of the glycine co-agonist site of the NMDAR.
Activation of NMDA receptors requires binding of glutamate or aspartate.
NMDARs also require the binding of the co-agonist glycine for the efficient opening of the ion channel.
D-Serine has also been found to co-agonize the NMDA receptor with even greater potency than glycine.
NMDA receptor agonists include:
Alanine
Aspartic acid
Glutamic acid
Glycine
Homocysteic acid
Serine (D-serine, L-serine)
Ketamine, a synthetic general anesthetic and one of the best-known NMDAR antagonists.
Physiological NMDA receptor activity is essential for normal neuronal function.
The blockage of NMDA receptor activity can result in adverse side effects such as hallucination, agitation and anesthesia.
Competitive NMDA receptor antagonists compete and bind to the same site (NR2 subunit) on the receptor as the agonist, glutamate, and therefore block normal function also.
NMDA receptor antagonists will block healthy areas of the brain prior to having an impact on pathological areas, as healthy areas have lower levels of agonist than pathological areas.
Under excitotoxic stress NMDA receptor antagonists can be displaced from the receptor by high concentration of glutamate.
Memantine is a derivative of amantadine which was first an anti-influenza agent but was later discovered by coincidence to have efficacy in Parkinson’s disease.
Memantine is an NMDA receptor antagonist.
Excitotoxicity that is involved in some neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis, theoretically can be blocked by inhibiting NMDA receptors.
Memantine is an uncompetitive NMDA receptor antagonist that has approved indication for the neurodegenerative disease Alzheimer’s disease.
The NMDA receptor is a non-specific cation channel that can allow the passage of Ca2+ and Na+ into the cell and K+ out of the cell.
The NMDA receptor increases the concentration of Ca2+ in the cell.
The Ca2+ can in turn function as a messenger in various signaling pathways.
The NMDA receptor cation channel is blocked by Mg2+ at resting membrane potential.
The NMDA receptor functions as a molecular coincidence detector, as its ion channel opens only when the following two conditions are met: glutamate is bound to the receptor, and the postsynaptic cell is depolarized removing the Mg2+ blocking the channel.
NMDA receptors are modulated by endogenous and exogenous compounds and play a key role in a wide range of physiological and pathological processes including memory, exotoxicity, respectively.
NMDA receptor antagonists like ketamine, esketamine,, phencyclidine, nitrous oxide, and xenon are used as general anesthetics.
NMDAR inhibitors, including ketamine, and esketamine.
Memantine, is a low-trapping NMDA receptor antagonist, for the treatment of moderate-to-severe Alzheimer’s disease.
NMDARs are associated with a rare autoimmune disease, anti-NMDA receptor encephalitis.
The NMDAR antagonist phencyclidine can produce a wider range of symptoms that resemble schizophrenia.
NMDA receptor antagonists are a class of drugs that may help treat Alzheimer’s disease, which causes memory loss, brain damage, and, eventually, death.
Glutamate neurotransmitter is passed from one neuron to another, it attaches itself to the new cell by using its known NMDA receptor.
When glutamate is at the NMDA receptor, it passes calcium into the cell, carrying the electrical or chemical signal important for learning and memory.
Memantine blocks some NMDA receptors when they are overactive.
The combination of memantine and a cholinesterase inhibitor leads to modest improvements in cognition and global outcomes in patients with advanced Alzheimer’s disease.
Other NMDA receptor antagonists include dextromethorphan, is a common ingredient in cough syrup.