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Currently, under the "Mechanism of action," the article states: "In any case, it has been elucidated that acute blockade of NMDA receptors in the brain results in an activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA receptors), which in turn modulate a variety of downstream signaling pathways to influence neurotransmission in the limbic system and mediate antidepressant effects of NMDA receptor antagonists like ketamine." The article does not address why the acute blockade of NMDA receptors in the brain results in an activation of AMPA receptors, which is very important to the explanation. The most accepted explanation of this appears to be due to a "glutamate surge".
This except explains it well: "Subanesthetic-dose ketamine administration leads to immediate presynaptic disinhibition of glutamatergic neurons, producing a glutamate surge (Moghaddam et al., 1997). This surge is thought to result from the blockade of NMDA receptors targeting γ-aminobutyric acid-ergic interneurons, leading to local inhibition of interneuron tonic firing and subsequent disinhibition of glutamate transmission (Homayoun and Moghaddam, 2007). Due to a blockade of NMDA receptors on postsynaptic excitatory neurons, excess synaptic glutamate is primarily taken up by AMPA receptors, thereby activating neuroplasticity-related signaling pathways (including mammalian target of rapamycin complex 1 (Li et al., 2010; Li et al., 2011) and brain-derived neurotrophic factor (Liu et al., 2012), both of which result in increased synaptogenesis and synaptic potentiation)." Gilbert JR, Yarrington JS, Wills KE, Nugent AC, Zarate CA (August 2018). "Glutamatergic Signaling Drives Ketamine-Mediated Response in Depression: Evidence from Dynamic Causal Modeling". The International Journal of Neuropsychopharmacology. 21 (8): 740–747. doi:10.1093/ijnp/pyy041. PMC6070027. PMID29668918.
I am thinking that the sentence should be changed to something to the effect of: "In any case, it has been elucidated that acute blockade of NMDA receptors in the brain results in an increase in glutamate production, which leads to an activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA receptors), which in turn modulate a variety of downstream signaling pathways to influence neurotransmission in the limbic system and mediate antidepressant effects of NMDA receptor antagonists like ketamine." Wikipedialuva (talk) 08:31, 11 October 2023 (UTC)[reply]
I think the long form chemical name of Ketamine (2-Cl-2’-oxo-PCM) should be added to the article. Who else has been looking for this information but can not find it? Daimontoppi (talk) 15:44, 5 November 2024 (UTC)[reply]
Nobody, because that's not the "long form" name. That's a weird abbreviation research chemical people came up with so they could look like they knew what they were doing as far as I can tell. All the instances in a search are forum posts from somewhere in eastern Europe and a thread on reddit asking if that should be the name of it. Ketamine variants are named using an etamine postfix with modified abbreviations for things like methoxetamine / methoxmetamine / ethketamine etc except when the chlorine atom is replaced and then you get things like 2-fluorodeschloroketamine. As soon as the cyclohexyl ring is replaced with a cyclohexanone the PCP style abbreviations aren't generally used anymore. A Shortfall Of Gravitas (talk) 06:43, 26 April 2025 (UTC)[reply]
level-5 vital article is rated B-class on Wikipedia's content assessment scale.
