Memantine
Systematic (IUPAC) name
1-amino-3,5-dimethyl-adamantane
Identifiers
CAS number	19982-08-2
ATC code	N06DX01
PubChem	4054
DrugBank	APRD00221
Chemical data
Formula	C12H21N
Mol. mass	179. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System containing Psychoanaleptics. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 3 g/mol
SMILES	eMolecules & PubChem
Pharmacokinetic data
Bioavailability	~100%
Metabolism	Hepatic (<10%)
Half life	60–100 hours
Excretion	Renal
Therapeutic considerations
Licence data	EU, US
Pregnancy cat.	B2 (Au), B (U.S.)
Legal status	S4 (Au), POM (UK), ℞-only (U. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during For a topic outline on this subject see List of basic Australia topics. The United States of America —commonly referred to as the The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom, the UK or Britain,is a Sovereign state located S. )
Routes	Oral

Memantine is the first in a novel class of Alzheimer's disease medications acting on the glutamatergic system by blocking NMDA glutamate receptors. In Pharmacology and Toxicology, a route Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. The glutamatergic Neurotransmitter system plays a crucial role in memory formation and information processing Memantine was first synthesized and patented by Eli Lilly and Company in 1968 (as cited in the Merck Index), and then developed by Merz in collaboration with Neurobiological Technologies, Inc. Merz Pharmaceuticals (Merz Pharma GmbH & Co KGaA) a member of Merz Pharma, is an international healthcare company specializing in the research development and licensed to Forest for the U. Forest Laboratories is a pharmaceutical company headquartered in New York City USA S. and Lundbeck for selected European and international markets. H Lundbeck A/S ( (also known as Lundbeck) is a Danish international Pharmaceutical company engaged in the Research and development, production Memantine is marketed under the brands Axura and Akatinol by Merz, Namenda by Forest , Ebixa and Abixa by Lundbeck and Memox by Unipharm.

Contents 1 Pharmacology 1.1 Glutamatergic (NMDA receptor) 1.2 Serotonergic (5-HT3 receptor) 1.3 Cholinergic (Nicotinic acetylcholine receptor) 1.4 Dopaminergic (D2 receptor) 2 Clinical use 2.1 Indications 2.2 Adverse drug reactions 3 See also 4 References 5 External links

Pharmacology

Glutamatergic (NMDA receptor)

A dysfunction of glutamatergic neurotransmission, manifested as neuronal excitotoxicity, is hypothesized to be involved in the etiology of Alzheimer's disease. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information Excitotoxicity is the pathological process by which nerve cells are damaged and killed by glutamate and similar substances Etiology (alternatively aetiology, aitiology) is the study of causation. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Targeting the glutamatergic system, specifically NMDA receptors, offers a novel approach to treatment in view of the limited efficacy of existing drugs targeting the cholinergic system. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its The NMDA receptor ( NMDAR) is an Ionotropic receptor for Glutamate ( NMDA ( N -methyl D -aspartate is a name of its selective The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central ^[1]

Memantine is a low-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. Uncompetitive inhibition takes place when an Enzyme inhibitor binds only to the complex formed between the Enzyme and the substrate (the E-S complex NMDA receptor antagonists are a class of Anesthetics that work to antagonize, or inhibit the action of the N-methyl d-aspartate receptor ( NMDAR ^[2][3] By binding to the NMDA receptor with a higher affinity than Mg²⁺ ions, memantine is able to inhibit the prolonged influx of Ca²⁺ ions which forms the basis of neuronal excitotoxicity. Magnesium (mægˈniːziəm is a Chemical element with the symbol Mg, Atomic number 12 Atomic weight 24 Calcium (ˈkælsiəm is the Chemical element with the symbol Ca and Atomic number 20 The low affinity and rapid off-rate kinetics of memantine at the level of the NMDA receptor-channel, however, preserves the physiological function of the receptor as it can still be activated by the relatively high concentrations of glutamate released following depolarization of the presynaptic neuron. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its In biology depolarization is a decrease in the Absolute value of a cell's Membrane potential. Chemical synapses are specialized junctions through which Neurons signal to each other and to non-neuronal cells such as those in Muscles or Glands ^[4][5] This unique molecular mechanism of action of memantine was first discovered by the laboratory of Stuart A. Lipton, MD, PhD, then at Harvard Medical School and now at the Burnham Institute for Medical Research in La Jolla, California. ^{[6][7][8][9][10]} The interaction of memantine with NMDA receptors plays a major role in the symptomatic improvement the drug produces in Alzheimer's disease. Moreover, there is no evidence as yet that the ability of memantine to protect against NMDA receptor-mediated excitotoxicity has a disease modifying effect in Alzheimer's, although this has been suggested in animal models. ^[5]

Serotonergic (5-HT₃ receptor)

Memantine acts as an uncompetitive antagonist at the 5HT₃ receptor, with a potency similar to that for the NMDA receptor. In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also ^[11] The clinical significance of this serotonergic activity in the treatment of Alzheimer's disease is unknown. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons

Cholinergic (Nicotinic acetylcholine receptor)

Memantine acts as an uncompetitive antagonist at different neuronal nicotinic neuronal receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses in these experiments. Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. ^[12][13][9] It has been shown that the number of nicotinic receptors in the brain are reduced in Alzheimer's disease, even in the absence of a general decrease in the number of neurons, and nicotinic receptor agonists are viewed as interesting targets for anti-Alzheimer drugs. An agonist is a term used to describe a type of ligand or drug that binds and alters the activity of a receptor. ^[14]

Dopaminergic (D2 receptor)

Memantine contains a dopaminergic component. ^[15]

Clinical use

Indications

Although memantine is approved for treatment of moderate to severe Alzheimer's Disease^[16] its usage has been recommended against by the UK's National Institute for Clinical Excellence,^[17] on the grounds that its high cost outweighs the benefits of treatment in most patients.

Memantine has been associated with a moderate decrease in clinical deterioration in Alzheimer's disease. ^[18] A systematic review of randomised controlled trials found that memantine has a small positive effect on cognition, mood, behaviour, and the ability to perform daily activities in moderate to severe Alzheimer's disease, but an unknown effect in mild to moderate disease. A randomized controlled trial (RCT is a type of scientific Experiment most commonly used in testing the Efficacy or Effectiveness of Healthcare Cognition is a concept used in different ways by different disciplines but is generally accepted to mean the process of awareness or thought ^[19]

Memantine is also being tested for Opioid dependence, systemic lupus erythematosus, depression, obsessive compulsive disorder, Attention-Deficit Hyperactivity Disorder (ADHD)^[20], glaucoma, tinnitus, neuropathic pain,^[21], pervasive developmental disorders, HIV associated Dementia^[22] and Nystagmus^[23]. Opioid dependency is a medical diagnosis characterized by an individual's inability to stop using opioids even when objectively in his or her best interest to do so Systemic lupus erythematosus ( SLE or lupus,) is a chronic autoimmune disease that can be fatal though with recent medical advances fatalities are becoming Major depressive disorder, also known as major depression, unipolar depression, unipolar disorder, clinical depression, or simply depression Obsessive-compulsive disorder (OCD is a Chronic Anxiety disorder most commonly characterized by obsessive Distressing Intrusive thoughts Attention-Deficit Hyperactivity Disorder (ADHD is a neurobehavioral developmental disorder affecting about 3-5% of the world's population Glaucoma is a group of diseases of the Optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. Tinnitus (tɪˈnaɪtəs or /ˈtɪnɪtəs/ from the Latin word for " Ringing " is the perception of sound within the human ear in the absence of corresponding Neuropathy is a medical term usually short for Peripheral neuropathy. The diagnostic category pervasive developmental disorders (PDD as opposed to Specific developmental disorders (SDD refers to a group of five disorders characterized Nystagmus is a type of eye movement characterized by alternating slow phase movements in one direction and Saccade -like quick phases in the other direction

Adverse drug reactions

Memantine is generally well-tolerated. ^[19] Common adverse drug reactions (≥1% of patients) include: confusion, dizziness, drowsiness, headache, insomnia, agitation, and/or hallucinations. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences Less common adverse effects include: vomiting, anxiety, hypertonia, cystitis, and increased libido. Hypertonia is an Upper motor neuron dysfunction marked by an abnormal increase in tightness of Muscle tone and a reduced ability of a muscle to stretch Cystitis is Inflammation of the Urinary bladder. The condition more often affects women but can affect either sex and all age groups Libido in its common usage means Sexual desire however more technical definitions such as those found in the work of Carl Jung, are more general referring to libido ^[24][18]

See also

• Alzheimer's disease
• Donepezil
• Galantamine
• Rivastigmine

References

External links

Namenda Memantine HCI [2]

• Lipton SA (2005). "The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: low-affinity, uncompetitive antagonism". Current Alzheimer research 2 (2): 155-65. doi:10.2174/1567205053585846. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15974913.  

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