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On the wiki page for NMDA it says that NMDA is a synthetic substance that mimics glutamate. So why does the body not use glutamate instead of NMDA?

Also how is it possible that our body can produce something that is synthetic? I thought synthetic was man-made chemicals. Does that mean the NMDA receptors it binds to are also synthetic? How did this come to be?

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(my comment reiterating the answer seemed useful, so I've reproduced it here)

There are "NMDA receptors" in our body. There is not NMDA naturally in our body*. "NMDA receptor" is just a name people gave to one of the receptors that normally binds glutamate. They could have called it something else, like the "slow glu receptor", or "Glutamate Receptor A", but they called it the NMDA receptor because they discovered it was different from other glutamate receptors in that it was activated by a chemical called NMDA in their experiments.


(original answer)

NMDA receptors are in fact glutamate receptors natively: there is no endogenous NMDA*. They are named NMDA receptors because experimentally they were differentiated from other glutamate receptors using the compound NMDA. At first glutamate receptors were known as "NMDA" and "non-NMDA" glutamate receptors, and later the non-NMDA sort were found to be sensitive to AMPA or kainate and named thusly.

Many other receptors are named this way: the nicotinic acetylcholine receptor is the receptor that nicotine is an agonist at, but the endogenous ligand is acetylcholine; muscarine is an agonist to the muscarinic acetylcholine receptor but the endogenous ligand is acetylcholine.


Watkins, J. C., & Jane, D. E. (2006). The glutamate story. British journal of pharmacology, 147(S1), S100-S108.


*In the comments, @gilleain pointed out some research suggesting that NMDA does exist endogenously, although in fairly specific areas and not disputing that glutamate is the primary endogenous agonist for NMDA receptors. This work was long after the NMDA-sensitive glutamate receptor was discovered and named, but is some interesting trivia nonetheless.

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    $\begingroup$ @user3665690 There are "NMDA receptors" in our body. There is not NMDA naturally in our body. "NMDA receptor" is just a name people gave to one of the receptors that normally binds glutamate. They could have called it something else, like the "slow glu receptor", or "Glutamate Receptor A", but they called it the NMDA receptor because they discovered it was different from other glutamate receptors in that it was activated by a chemical called NMDA in their experiments. $\endgroup$ – Bryan Krause Apr 30 at 1:02
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    $\begingroup$ I see! ok that makes a lot of sense now, so basically NMDA is a synthetic chemical that mimics glutamate induce NMDA receptor activity. Is that the right interpretation? $\endgroup$ – user3665690 Apr 30 at 1:07
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    $\begingroup$ @user3665690 Yes that's correct $\endgroup$ – Bryan Krause Apr 30 at 1:31
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    $\begingroup$ ncbi.nlm.nih.gov/pubmed/11014243 : " we show that N-methyl-D-aspartate (NMDA) is present at nanomolar levels in rat nervous system and endocrine glands as a natural compound, and it is biosynthesized in vivo and in vitro. " but anyway that's beside the point - the question includes "Also how is it possible that our body can produce something that is synthetic?" $\endgroup$ – gilleain Apr 30 at 15:36
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    $\begingroup$ @gilleain Thanks for the reference! Quite interesting, I'll have to look into related work and possibly change my worldview a bit. $\endgroup$ – Bryan Krause Apr 30 at 15:41
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There is no clear-cut line between "synthetic" and "natural" substances. They are made from the same kinds of atoms using the same kinds of covalent, ionic, and other types of bonds. The fact that a substance MAY be produced by some organism by biological processes does not make it any different from the same substance made in a laboratory by a human chemist from non-living reactants. What is relevant is the precise structure of the substance and the impurities that may be present in a particular sample of it. Sometimes, because of the details of the kinetics and thermodynamics of biosynthetic and human laboratory synthetic processes, the relative isotopic composition of one or more of the elements may be different, but that can also be true of different "natural" processes and different "synthetic" processes.

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