Editing AMPA receptor (section)

==Role in epileptic seizures==
AMPA receptors play a key role in the generation and spread of [[epileptic seizures]].<ref>
{{cite journal | vauthors = Rogawski MA | title = AMPA receptors as a molecular target in epilepsy therapy | journal = Acta Neurologica Scandinavica. Supplementum | volume = 127 | issue = 197 | pages = 9–18 | year = 2013 | pmid = 23480151 | pmc = 4506648 | doi = 10.1111/ane.12099 }}</ref> Activation of AMPARs by agonists such as [[Kainate|kainic acid]], a convulsant that is widely used in epilepsy research,<ref>{{cite journal | vauthors = Fritsch B, Reis J, Gasior M, Kaminski RM, Rogawski MA | title = Role of GluK1 kainate receptors in seizures, epileptic discharges, and epileptogenesis | journal = The Journal of Neuroscience | volume = 34 | issue = 17 | pages = 5765–75 | date = April 2014 | pmid = 24760837 | pmc = 3996208 | doi = 10.1523/JNEUROSCI.5307-13.2014 }}</ref> has been shown to induce seizures in both animal models and humans, emphasizing their contribution to epileptogenesis.  Conversely, antagonists targeting AMPARs have demonstrated efficacy in suppressing seizure activity, highlighting their potential as therapeutic agents in epilepsy management.<ref>{{Cite journal |last=Hanada |first=Takahisa |date=2020-03-18 |title=Ionotropic Glutamate Receptors in Epilepsy: A Review Focusing on AMPA and NMDA Receptors |journal=Biomolecules |language=en |volume=10 |issue=3 |pages=464 |doi=10.3390/biom10030464 |doi-access=free |issn=2218-273X |pmc=7175173 |pmid=32197322}}</ref>

===Molecular target for epilepsy therapy===
The noncompetitive AMPA receptor antagonists [[talampanel]] and [[perampanel]] have been demonstrated to have activity in the treatment of adults with partial-onset seizures,<ref name="Bialer">{{cite journal | vauthors = Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T | title = Progress report on new antiepileptic drugs: a summary of the Eighth Eilat Conference (EILAT VIII) | journal = Epilepsy Research | volume = 73 | issue = 1 | pages = 1–52 | date = January 2007 | pmid = 17158031 | doi = 10.1016/j.eplepsyres.2006.10.008 | s2cid = 45026113 }}</ref><ref name="French">{{cite journal | vauthors = French JA, Krauss GL, Biton V, Squillacote D, Yang H, Laurenza A, Kumar D, Rogawski MA | display-authors = 6 | title = Adjunctive perampanel for refractory partial-onset seizures: randomized phase III study 304 | journal = Neurology | volume = 79 | issue = 6 | pages = 589–96 | date = August 2012 | pmid = 22843280 | pmc = 3413761 | doi = 10.1212/WNL.0b013e3182635735 }}</ref> indicating that AMPA receptor antagonists represent a potential target for the treatment of [[epilepsy]].<ref name="Rogawski">{{cite journal | vauthors = Rogawski MA | title = Revisiting AMPA receptors as an antiepileptic drug target | journal = Epilepsy Currents | volume = 11 | issue = 2 | pages = 56–63 | date = March 2011 | pmid = 21686307 | pmc = 3117497 | doi = 10.5698/1535-7511-11.2.56 }}</ref>
<ref name="Rogawski-b">{{cite journal | vauthors = Sakai F, Igarashi H, Suzuki S, Tazaki Y | title = Cerebral blood flow and cerebral hematocrit in patients with cerebral ischemia measured by single-photon emission computed tomography | journal = Acta Neurologica Scandinavica. Supplementum | volume = 127 | pages = 9–13 | year = 1989 | pmid = 2631521 | doi = 10.1111/j.1600-0404.1989.tb01805.x | s2cid = 30934688 | doi-access = free }}</ref> Perampanel (trade name: Fycompa) received Marketing Authorisation Approval by the European Commission for the treatment of partial epilepsy on July 27, 2012. The drug was approved in the United States by the [[Food and Drug Administration]] (FDA) on October 22, 2012. As has been the case for most recently developed AEDs including [[pregabalin]], [[lacosamide]] and [[ezogabine]], the FDA recommended that perampanel be classified by the [[Drug Enforcement Administration]] (DEA) as a scheduled drug. It has been designated as a Schedule 3 controlled substance.

[[Decanoic acid]] acts as a non-competitive AMPA receptor antagonist at therapeutically relevant concentrations, in a voltage- and subunit-dependent manner, and this is sufficient to explain its antiseizure effects.<ref name= awv325>{{cite journal | vauthors = Chang P, Augustin K, Boddum K, Williams S, Sun M, Terschak JA, Hardege JD, Chen PE, Walker MC, Williams RS | display-authors = 6 | title = Seizure control by decanoic acid through direct AMPA receptor inhibition | journal = Brain | volume = 139 | issue = Pt 2 | pages = 431–43 | date = February 2016 | pmid = 26608744 | pmc = 4805082 | doi = 10.1093/brain/awv325 }}</ref> This direct inhibition of excitatory neurotransmission by decanoic acid in the brain contributes to the anticonvulsant effect of the [[medium-chain triglyceride]] [[ketogenic diet]].<ref name=awv325/> Decanoic acid and the AMPA receptor antagonist drug perampanel act at separate sites on the AMPA receptor, and so it is possible that they have a cooperative effect at the AMPA receptor, suggesting that perampanel and the ketogenic diet could be synergistic.<ref name=awv325/><ref>{{cite journal | doi=10.1111/epi.14578 | title=Perampanel and decanoic acid show synergistic action against <SCP>AMPA</SCP> receptors and seizures | date=2018 | last1=Augustin | first1=Katrin | last2=Williams | first2=Sophie | last3=Cunningham | first3=Mark | last4=Devlin | first4=Anita M. | last5=Friedrich | first5=Maximilian | last6=Jayasekera | first6=Ashan | last7=Hussain | first7=Mohammed A. | last8=Holliman | first8=Damian | last9=Mitchell | first9=Patrick | last10=Jenkins | first10=Alistair | last11=Chen | first11=Philip E. | last12=Walker | first12=Matthew C. | last13=Williams | first13=Robin S.B. | journal=Epilepsia | volume=59 | issue=11 | pages=e172–e178 | pmid=30324610 | doi-access=free }}</ref>

Preclinical research suggests that several derivatives of aromatic amino acids with antiglutamatergic properties including AMPA receptor antagonism and inhibition of glutamate release such as 3,5-dibromo-D-tyrosine and 3,5-dibromo-L-phenylalnine exhibit strong anticonvulsant effect in animal models suggesting use of these compounds as a novel class of antiepileptic drugs.<ref>{{cite journal | vauthors = Cao W, Shah HP, Glushakov AV, Mecca AP, Shi P, Sumners C, Seubert CN, Martynyuk AE | display-authors = 6 | title = Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit | journal = British Journal of Pharmacology | volume = 158 | issue = 8 | pages = 2005–13 | date = December 2009 | pmid = 20050189 | pmc = 2807662 | doi = 10.1111/j.1476-5381.2009.00498.x }}</ref><ref>{{cite journal | vauthors = Cao W, Glushakov A, Shah HP, Mecca AP, Sumners C, Shi P, Seubert CN, Martynyuk AE | display-authors = 6 | title = Halogenated aromatic amino acid 3,5-dibromo-D: -tyrosine produces beneficial effects in experimental stroke and seizures | journal = Amino Acids | volume = 40 | issue = 4 | pages = 1151–8 | date = April 2011 | pmid = 20839013 | doi = 10.1007/s00726-010-0739-4 | s2cid = 19852158 | pmc = 8396070 }}</ref>