Memantine

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Memantine
Memantine.svg
Chemical Nomenclature
Common names Memantine, Memaxa, Ebixa, Namenda, Namenda XR, Namzaric (with donepezil, both extended-release)
Substitutive name Memantine
Systematic name 3,5-Dimethyladamantan-1-amine
Class Membership
Psychoactive class Dissociative
Chemical class Adamantane
Routes of Administration

WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.



Oral
Dosage
Threshold Common Heavy
10 - 30 - 80 - 100 - 150 mg
Light Strong
Threshold 10 - 30 mg
Light 30 - 80 mg
Common 80 - 100 mg
Strong 100 - 150 mg
Heavy 150 mg +
Duration
Total 48 - 72 hours
Onset 40 - 180 minutes
Peak 3 - 24 hours
Offset 24 - 48 hours









DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.

Summary sheet: Memantine

Memantine is a dissociative substance of the adamantane class that produces long-lived dissociative effects when administered. It is a derivative of amantadine and is pharmacologically related to compounds like PCP, ketamine, and DXM, although its recreational use is comparatively rare.

Memantine was first synthesized by Eli Lilly and Company in 1968 as a potential agent to treat diabetes.[citation needed]

Memantine is classified as an NMDA receptor antagonist. This means it binds to and blocks the signaling of excitatory receptors in the central nervous system. These compounds induce a state known as "dissociative-anesthesia," which has a number of hallucinogenic attributes.

In medicine, memantine is used primarily in humans in the treatment of neurodegenerative diseases like Alzheimer's disease. It also has seen use as a nootropic for its cognitive-enhancing effects.

Chemistry

Memantine, or 3,5-dimethyladamantan-1-amine, is a man-made molecule classified as a substituted adamantane derivative. Its core structure is adamantane, a diamondoid of four interlocked cyclohexane rings in a stable 3-dimensional lattice conformation. Memantine is substituted with a methyl carbon at both R3 and R5; it contains an amine substitution at R1. Its name is derived from its structure; 3,5-dimethyladamantan-1-amine.

Pharmacology

Glutamatergic (NMDA receptor)
Further information: NMDA receptor antagonist

Memantine is a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.[1] NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “hole”.

Memantine is distinct from most other dissociatives due to its fast, voltage-dependent binding kinetics that allow for functional ionic transmission through the NMDA receptors unless in the presence of a large enough concentration of agonists, causing memantine to be more similar in pharmacodynamical profile at the NMDA receptor to endogenous magnesium than to other dissociatives. Memantine's unique pharmacological profile allows it to elicit neuroprotective properties at doses that lack strong amounts of impairment, making it useful in the treatment of neurodegenerative disorders.

Serotonergic (5-HT3 receptor)

Memantine acts as a non-competitive antagonist at the 5-HT3 receptor, with a potency similar to that for the NMDA receptor.

Cholinergic (nicotinic acetylcholine receptor)

Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine 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. Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.

Dopaminergic (D2 receptor)

Memantine acts as an agonist at the dopamine D2 receptor with equal or slightly higher affinity than to the NMDA receptors.

Sigmaergic (σ1 receptor)

It acts as an agonist at the σ1 receptor with a low Ki of 2.6 µM. The effects of this activity are unclear (as the role of sigma receptors, in general, is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism.

Subjective effects

The effects listed below are based upon the subjective effects index and personal experiences of PsychonautWiki contributors. The listed effects should be taken with a grain of salt and will rarely (if ever) occur all at once, but heavier doses will increase the chances and are more likely to induce a full range of effects. Likewise, adverse effects become much more likely on higher doses and may include serious injury or death.

Physical effects
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Visual effects
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Disconnective effects
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Toxicity and harm potential

The toxicity and long-term health effects of recreational memantine use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown, although up to 400mg has been tolerated.[2] This is because memantine has very little history of recreational human usage.

Anecdotal evidence from people who have tried memantine within the community suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Tolerance and addiction potential

The dependence potential for memantine is unknown. However, due to its long duration and long onset, users are discouraged to redose, meaning it is unlikely users will develop an addiction.

Memantine presents cross-tolerance with all dissociatives, meaning that after the consumption of memantine all dissociatives will have a reduced effect.

Dangerous interactions

Memantine has very limited information on drug combinations and should therefore be treated with extreme caution when combined with other drugs.

Although many psychoactive substances are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.

Prominent examples include PCP and its analogs 3-MeO-PCP, MXE, and the diarylethylamine dissociatives like diphenidine or ephenidine. There is also evidence that suggests that combining these two increases their neurotoxicity.[citation needed] Anecdotally, worsened comedowns are also commonly reported when these two classes of substances are combined.

Other interactions

  • Nicotine - Anecdotal reports suggest an interaction between tobacco and memantine.
  • Opioids - Memantine is reported to increase the effects, prevent build up and in some cases reverse tolerance to opioids.
  • Stimulants - Memantine is reported to increase the effects, prevent build up and in some cases reverse tolerance to stimulants.
  • Alcohol - Memantine is reported to increase the effects, prevent build up and, in some cases, reverse tolerance to alcohol.

Legal status

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This legality section is a stub.

As such, it may contain incomplete or wrong information. You can help by expanding it.

  • Australia: Memantine is S4, meaning it is available only with a prescription.[citation needed]
  • United Kingdom: Memantine is a POM (prescription-only medicine).[citation needed]
  • United States: Memantine is only available through a prescription.[citation needed]

See also

External links

Literature

  • Lipton, S. A. (2006). Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nature Reviews Drug Discovery, 5(2), 160. https://doi.org/10.1038/nrd1958
  • Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620

References

  1. Parsons, C. G., Rammes, G., & Danysz, W. (2008). Pharmacodynamics of memantine: an update. Current neuropharmacology, 6(1), 55-78. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645549/?report=classic
  2. http://www.drugbank.ca/drugs/DB01043