NMDA receptor antagonist

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NMDA receptor antagonists are a class of psychoactive substances that work by antagonizing, or inhibiting the action of, the NMDA receptor (NMDAR). The NMDA receptor is one of the receptor types for glutamate which is one of the principal excitatory neurotransmitters and is involved in cognitive functions such as learning and memory.[1]

NMDA receptor antagonists are used as anesthetics for animals and for humans; the state of anesthesia they induce is referred to as dissociative anesthesia.[citation needed] Some NMDA receptor antagonists, such as ketamine, dextromethorphan (DXM), phencyclidine (PCP), and nitrous oxide (N2O), are popular recreational drugs used for their dissociative, hallucinogenic, and euphoric effects. When used recreationally, they are classified as dissociative drugs.

There is evidence that NMDA receptor antagonists can cause a certain type of neurotoxicity or brain damage referred to as Olney's Lesions in rodents, although such damage has never been conclusively observed in primates like humans. Recent research conducted on primates suggests that, while very consistent and long-term ketamine use may be neurotoxic, acute use is not.[2][3]

Several synthetic opioids function additionally as NMDAR antagonists, such as pethidine, methadone, dextropropoxyphene, tramadol and ketobemidone.

Mechanism of action

The NMDA receptor is a receptor that allows for the transfer of electrical signals between neurons in the brain and in the spinal column. For electrical signals to pass, the NMDA receptor must be open. To remain open, glutamate and glycine must bind to the NMDA receptor. An NMDA receptor that has glycine and glutamate bound to it and has an open ion channel is called "activated."

Chemicals that deactivate the NMDA receptor are called antagonists. NMDAR antagonists fall into four categories:

  • Competitive antagonists, which bind to and block the binding site of the neurotransmitter glutamate
  • Glycine antagonists, which bind to and block the glycine site
  • Noncompetitive antagonists, which inhibit NMDARs by binding to allosteric sites
  • Uncompetitive antagonists, which block the ion channel by binding to a site within it.[4]

Once a sufficient amount of NMDA receptors have been deactivated, the result is a dosage dependent decrease in the passing of electrical signals across the brain and a disconnection of neurons. This leads to states of disconnection between conscious parts of the brain, anesthesia and its sensory organs as well as out-of-body experiences and accompanying hallucinations.







Toxicity and harm potential


This toxicity and harm potential section is a stub.

As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
Note: Always conduct independent research and use harm reduction practices if using this substance.

Dependence and abuse potential

Dissociatives are generally considered to have moderate to high abuse potential.

Dangerous interactions

See also

External links


  1. McEntee, W. J., Crook, T. H. (July 1993). "Glutamate: its role in learning, memory, and the aging brain". Psychopharmacology. 111 (4): 391–401. doi:10.1007/BF02253527. ISSN 0033-3158. 
  2. Sun, L., Li, Q., Li, Q., Zhang, Y., Liu, D., Jiang, H., Pan, F., Yew, D. T. (March 2014). "Chronic ketamine exposure induces permanent impairment of brain functions in adolescent cynomolgus monkeys". Addiction Biology. 19 (2): 185–194. doi:10.1111/adb.12004. ISSN 1369-1600. 
  3. Slikker, W., Zou, X., Hotchkiss, C. E., Divine, R. L., Sadovova, N., Twaddle, N. C., Doerge, D. R., Scallet, A. C., Patterson, T. A., Hanig, J. P., Paule, M. G., Wang, C. (10 April 2007). "Ketamine-Induced Neuronal Cell Death in the Perinatal Rhesus Monkey". Toxicological Sciences. 98 (1): 145–158. doi:10.1093/toxsci/kfm084. ISSN 1096-6080. 
  4. Kim, A. H., Kerchner, G. A., Choi, D. W. (2002). "CNS Neuroprotection". In Marcoux, F. W., Choi, D. W. Blocking Excitotoxicity. Handbook of Experimental Pharmacology. Springer. pp. 3–36. doi:10.1007/978-3-662-06274-6_1. ISBN 9783662062746.